1537-2073-17_s1_1.pdf - Allen Press

The Official Publication of the Consortium of Multiple Sclerosis Centers

May 2015 • Volume 17, Supplement 1 2015

Official Abstracts

ijmsc.org

2015 Annual Meeting of the CMSC

Abstracts from the 29th Annual Meeting of the

Consortium of Multiple Sclerosis Centers

27 May 2015 to 30 May 2015

Indianapolis, Indiana

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This Product Theater is a promotional activity and is not approved for continuing education credit. The content of this Product Theater and opinions expressed by the presenters are those of the corporate supporter and faculty and not of the Consortium of Multiple Sclerosis Centers.

©2015 Genzyme Corporation, a Sanofi company. All rights reserved. GZUS.MS.15.03.0732

www.genzyme.com

Cases in MS: Selecting Appropriate Treatment Options for Patients

Visit BOOTH 101 to learn more.

Multiple sclerosis is not just a disease—it’s a challenge

The Management of Infusions in Patients with Relapsing MS W H E N Friday, May 29, 2015

W H E R E JW Marriott Indianapolis, White River Ballroom, G-J

T I M E 7:00 am-8:00 am (Breakfast included)

Christina Caon, RN, MSN, NP-CHarper University Hospital, Detroit, Michigan; Assistant Director of Clinical Research at the Wayne State University MS Program, Detroit, Michigan

P R E S E N T E R S Lori MayerDirector of Medical Research Services, Central Texas Consultants, MS Clinic of Central Texas, Round Rock, Texas

W H E N Thursday, May 28, 2015

W H E R E JW Marriott Indianapolis Grand Ballroom—Exhibit Hall, Product Theater Area

T I M E 7:00 pm-8:00 pm

Ann D. Bass, MDMS Clinic DirectorNeurology Center of San Antonio, P.A.San Antonio, Texas

Amy L. Genzyme Patient Ambassador

P R E S E N T E R P A N E L I S T S Stacey J. Genzyme PatientAmbassador

Genzyme continues to provide support for your MS patients

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International Journal of MS Careiv

May 2015 • Vol. 17, Suppl. 1

Cover photo credit: Kevin Foster

We are pleased to present this supplement to the International Journal of MS Care (IJMSC) containing the abstracts from the 2015 Annual Meeting of the

Consortium of Multiple Sclerosis Centers (CMSC), held from May 27 through 30, 2015, in Indianapolis, Indiana. These abstracts include platform, poster, and Whitaker Research Track presentations delivered at the meeting. If you were not able to attend the conference, this is a wonderful opportunity for you to appreciate the diversity and depth of this outstanding group of presentations. The print version of this supplement is being distributed at the CMSC meeting in Indianapolis to meeting attendees. The electronic version, which is available to all on the IJMSC website at ijmsc.org, can be searched using key words to identify abstracts on topics of individual interest.

We would like to thank Genzyme for their support, which made this publication possible.

We hope that this material will assist you in your care of MS patients and stimulate your interest in furthering research and care in MS.

—Francois Bethoux, MDEditor in Chief

2015 Annual Meeting of the CMSC

Editorial Board

Editor in ChiEf

Francois Bethoux, MDCleveland Clinic

Cleveland, Ohio, USA

Ex offiCio

June Halper, MSN, ANP, FAANHackensack, New Jersey, USA

ProjECt ManagEr

Maria Stadtler, CCRPCleveland Clinic


Board MEMBErs

Ted Brown, MD, MPHEvergreen Neuroscience Institute and

Medical CenterKirkland, Washington, USA

Susan Coote, PT, PhDUniversity of Limerick

Limerick, Ireland

Mary Filipi, PhD, ARNPUniversity of Nebraska Medical Center

Omaha, Nebraska, USA

Marcia Finlayson, PhD, OT Reg (Ont), OTRQueen’s University

Kingston, Ontario, Canada

Frederick W. Foley, PhDYeshiva University

Bronx, New York, USAHoly Name Medical CenterTeaneck, New Jersey, USA

Kathleen Fuchs, PhDUniversity of Virginia Health System

Charlottesville, Virginia, USA

Eduard Gappmaier, PT, PhDUniversity of Utah

Salt Lake City, Utah, USA

Christoph Heesen, MDInstitute of Neuroimmunology and

Clinical MS ResearchUniversity Medical Center

Hamburg, Germany

James Marriott, MD, FRCPCUniversity of Manitoba

Winnipeg, Manitoba, Canada

Lori Mayer, MSN, DNP(s), MSCN, CCRPMS Clinic of Central TexasRound Rock, Texas, USA

Sarah Morrow, MD, MSc, FRCPCUniversity of Western OntarioLondon Health Sciences Centre

London, Ontario, Canada

Priscilla Russo, MS, RN, MSCN, CCRCCarolinas Medical Center

Charlotte, North Carolina, USA

Megan Weigel, DNP, ARNP-cBaptist Medical Center

Jacksonville Beach, Florida, USA

Mary Alissa Willis, MDCleveland Clinic


PuBlishErs

Joseph J. D’OnofrioFrank M. Marino

Delaware Media Group66 S. Maple Ave., Ridgewood, NJ 07450

[email protected]

Managing Editor

Annette Theuring

art dirECtor

James Ticchio

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355 Park Ave South, New York, NY 10010 | 212-822-4646

GZUS.AUBA.15.03.0728_04-14244H_CMSC_Ad_188796_7v2_fnlModifi ed: March 18, 2015 11:44 AM

Bleed 8” x 11”

Trim 7.75” x 10.75”

Safety 7.25” x 10.25”

Finished 7.75” x 10.75”

MS=multiple sclerosis.

S:7.25”S:10.25”

T:7.75”T:10.75”

B:8”B:11”

GZUS.AUBA.15.03.0728_04-14244H_CMSC_Ad_188796_7v2_fnl.indd 1 3/18/15 12:04 PM

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GZUS.AUBA.15.03.0728_04-14244H_CMSC_Ad_188796_7v2_fnlModified: March 18, 2015 11:44 AM

Bleed 15.75” x 11”

Trim 15.5” x 10.75”

Safety 15” x 10.25”

Finished 15.5” x 10.75”

INDICATION

AUBAGIO® (teriflunomide) is indicated for the treatment of patients with relapsing forms of multiple sclerosis.

IMPORTANT SAFETY INFORMATIONWARNING: HEPATOTOXICITY AND RISK OF TERATOGENICITYSevere liver injury including fatal liver failure has been reported in patients treated with leflunomide, which is indicated for rheumatoid arthritis. A similar risk would be expected for teriflunomide because recommended doses of teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide. AUBAGIO is contraindicated in patients with severe hepatic impairment and in patients taking leflunomide. Concomitant use of AUBAGIO with other potentially hepatotoxic drugs may increase the risk of severe liver injury. Obtain transaminase and bilirubin levels within 6 months before initiation of AUBAGIO therapy. Monitor ALT levels at least monthly for 6 months after starting AUBAGIO. If drug-induced liver injury is suspected, discontinue AUBAGIO and start an accelerated elimination procedure with cholestyramine or charcoal. Patients with pre-existing liver disease may be at increased risk of developing elevated serum transaminases when taking AUBAGIO.Based on animal data, AUBAGIO may cause major birth defects if used during pregnancy. Pregnancy must be excluded before starting AUBAGIO. AUBAGIO is contraindicated in pregnant women or women of childbearing potential who are not using reliable contraception. Pregnancy must be avoided during AUBAGIO treatment or prior to the completion of an accelerated elimination procedure after AUBAGIO treatment.

Warnings and PrecautionsPatients with pre-existing acute or chronic liver disease, or those with serum ALT >2 times the upper limit of normal (ULN) before initiating treatment, should not normally be treated with AUBAGIO. In clinical trials, if ALT elevation was >3 times the ULN on 2 consecutive tests, patients discontinued AUBAGIO and underwent accelerated elimination. Consider additional monitoring if co-administering AUBAGIO with other potentially hepatotoxic drugs; monitor patients who develop symptoms suggestive of hepatic dysfunction (eg, unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine).Before starting therapy, use of reliable contraception must be confirmed, and the patient counseled on risks to the fetus. Patients with delayed onset of menses or other reason to suspect pregnancy should immediately see their physician for pregnancy testing. Patients who become pregnant or wish to become pregnant should discontinue treatment, followed by accelerated elimination until plasma concentrations of <0.02 mcg/mL are verified, a level expected to pose minimal risk to the fetus. Women who become pregnant while taking AUBAGIO may enroll in the AUBAGIO pregnancy registry by calling 1-800-745-4447, option 2.Teriflunomide is eliminated slowly from the plasma—it takes an average of 8 months, or up to 2 years, to reach plasma concentrations <0.02 mcg/mL. Elimination may be accelerated by administration of cholestyramine or charcoal, but this may cause disease activity to return in patients who were responding to AUBAGIO.Decreases in white blood cell counts, mainly of neutrophils and lymphocytes, and platelets have been reported with AUBAGIO. Obtain a complete blood cell

count within 6 months before starting treatment, with further monitoring based on signs and symptoms of bone marrow suppression. AUBAGIO is not recommended for patients with severe immunodeficiency, bone marrow disease, or severe uncontrolled infections. Tuberculosis (TB) has been observed in clinical studies of AUBAGIO. Before starting treatment, screen patients for latent TB infection with a tuberculin test. Treatment in patients with acute or chronic infections should not be started until the infection(s) is resolved. Administration of live vaccines is not recommended. The risk of malignancy, particularly lymphoproliferative disorders, or infection may be increased with the use of some medications with immunosuppressive potential, including teriflunomide.Peripheral neuropathy, including polyneuropathy and mononeuropathy, has been reported with AUBAGIO. Age >60 years, concomitant neurotoxic medications, and diabetes may increase the risk. If peripheral neuropathy is suspected, consider discontinuing treatment and performing accelerated elimination.Interstitial lung disease and rare cases of Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with leflunomide; a similar risk would be expected for teriflunomide. If a severe skin reaction develops with AUBAGIO, stop treatment and use accelerated elimination.Blood pressure increases and hypertension have occurred with AUBAGIO. Measure blood pressure at treatment initiation and manage any elevations during treatment.

Adverse Reactions: The most frequent adverse reactions (≥10% and ≥2% greater than placebo) with AUBAGIO 7 mg and 14 mg and placebo, respectively, were headache (18% and 16% vs 15%), ALT increased (13% and 15% vs 9%), diarrhea (13% and 14% vs 8%), alopecia (10% and 13% vs 5%), and nausea (8% and 11% vs 7%).Drug Interactions: Monitor patients when teriflunomide is coadministered with warfarin, or with drugs metabolized by CYP1A2, CYP2C8, substrates of OAT3 transporters, substrates of BCRP, or OATP1B1/1B3 transporters.Use in Specific Populations: AUBAGIO is detected in human semen. To minimize any possible fetal risk, men not wishing to father a child and their female partners should use reliable contraception. Men wishing to father a child should discontinue therapy and undergo accelerated elimination, with verification of plasma concentrations <0.02 mcg/mL. Nursing mothers should not use AUBAGIO.Please see Brief Summary of Full Prescribing Information, including boxed WARNING regarding hepatotoxicity and use in pregnancy, on the following pages.

AUBAGIO® (teriflunomide) was proven again and again to reduce key measures of disease activity: sustained disability progression (14 mg only), annualized relapse rate, and MRI activity1

AUBAGIO 14 mg is the only oral MS therapy with 2 pivotal Phase III trials that show a significant reduction in the risk of sustained disability accumulation1,3,4

— AUBAGIO 7 mg did not demonstrate a significant reduction in risk of sustained disability progression in either trial1

AUBAGIO has demonstrated a consistent safety profile across 4 separate trials in 2047 patients1

One daily tablet that can be taken anytime, anyplace1

TEMSO: A double-blind, placebo-controlled trial in patients with relapsing forms of MS (N=1088). Patients were randomized to receive AUBAGIO 14 mg (n=359), AUBAGIO 7 mg (n=366), or placebo (n=363) once daily for 108 weeks.1

TOWER: A double-blind, placebo-controlled trial in patients with relapsing forms of MS (N=1169). Patients were randomized to receive AUBAGIO 14 mg (n=372), AUBAGIO 7 mg (n=408), or placebo (n=389) once daily with results for up to 40 months of treatment.1,5

TOPIC: A double-blind, placebo-controlled clinical trial in patients with relapsing MS (N=618). Patients were randomized to receive AUBAGIO 14 mg (n=216), AUBAGIO 7 mg (n=205), or placebo (n=197) once daily for 108 weeks. Patients had a first clinical event consistent with acute demyelination occurring within 90 days of randomization with 2 or more T2 lesions at least 3 mm in diameter characteristic of MS.1,6

Study 4: A randomized, double-blind, placebo-controlled trial in patients with relapsing forms of MS (N=179). Patients were randomized to receive AUBAGIO 14 mg (n=57), AUBAGIO 7 mg (n=61), or placebo (n=61) once daily for 36 weeks.1

* AUBAGIO is effective across key measures of disease activity: sustained disability progression (14 mg only), annualized relapse rate, and MRI activity. Common adverse events with AUBAGIO led to treatment discontinuation rates ≤3.3% in the pooled clinical trials.1,2

QUIETING MS

for your patients with relapsing MS

Quietly *

S:15”

S:10.25”

T:15.5”

T:10.75”

B:15.75”

B:11”

F:7.75”

FS:7.25”

F:7.75”

FS:7.25”

GZUS.AUBA.15.03.0728_04-14244H_CMSC_Ad_188796_7v2_fnl.indd 2-3 3/18/15 12:04 PM

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GZUS.AUBA.15.03.0728_04-14244H_CMSC_Ad_188796_7v2_fnlModified: March 18, 2015 11:44 AM

Bleed 15.75” x 11”

Trim 15.5” x 10.75”

Safety 15” x 10.25”

Finished 15.5” x 10.75”

INDICATION

AUBAGIO® (teriflunomide) is indicated for the treatment of patients with relapsing forms of multiple sclerosis.

IMPORTANT SAFETY INFORMATIONWARNING: HEPATOTOXICITY AND RISK OF TERATOGENICITYSevere liver injury including fatal liver failure has been reported in patients treated with leflunomide, which is indicated for rheumatoid arthritis. A similar risk would be expected for teriflunomide because recommended doses of teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide. AUBAGIO is contraindicated in patients with severe hepatic impairment and in patients taking leflunomide. Concomitant use of AUBAGIO with other potentially hepatotoxic drugs may increase the risk of severe liver injury. Obtain transaminase and bilirubin levels within 6 months before initiation of AUBAGIO therapy. Monitor ALT levels at least monthly for 6 months after starting AUBAGIO. If drug-induced liver injury is suspected, discontinue AUBAGIO and start an accelerated elimination procedure with cholestyramine or charcoal. Patients with pre-existing liver disease may be at increased risk of developing elevated serum transaminases when taking AUBAGIO.Based on animal data, AUBAGIO may cause major birth defects if used during pregnancy. Pregnancy must be excluded before starting AUBAGIO. AUBAGIO is contraindicated in pregnant women or women of childbearing potential who are not using reliable contraception. Pregnancy must be avoided during AUBAGIO treatment or prior to the completion of an accelerated elimination procedure after AUBAGIO treatment.

Warnings and PrecautionsPatients with pre-existing acute or chronic liver disease, or those with serum ALT >2 times the upper limit of normal (ULN) before initiating treatment, should not normally be treated with AUBAGIO. In clinical trials, if ALT elevation was >3 times the ULN on 2 consecutive tests, patients discontinued AUBAGIO and underwent accelerated elimination. Consider additional monitoring if co-administering AUBAGIO with other potentially hepatotoxic drugs; monitor patients who develop symptoms suggestive of hepatic dysfunction (eg, unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine).Before starting therapy, use of reliable contraception must be confirmed, and the patient counseled on risks to the fetus. Patients with delayed onset of menses or other reason to suspect pregnancy should immediately see their physician for pregnancy testing. Patients who become pregnant or wish to become pregnant should discontinue treatment, followed by accelerated elimination until plasma concentrations of <0.02 mcg/mL are verified, a level expected to pose minimal risk to the fetus. Women who become pregnant while taking AUBAGIO may enroll in the AUBAGIO pregnancy registry by calling 1-800-745-4447, option 2.Teriflunomide is eliminated slowly from the plasma—it takes an average of 8 months, or up to 2 years, to reach plasma concentrations <0.02 mcg/mL. Elimination may be accelerated by administration of cholestyramine or charcoal, but this may cause disease activity to return in patients who were responding to AUBAGIO.Decreases in white blood cell counts, mainly of neutrophils and lymphocytes, and platelets have been reported with AUBAGIO. Obtain a complete blood cell

count within 6 months before starting treatment, with further monitoring based on signs and symptoms of bone marrow suppression. AUBAGIO is not recommended for patients with severe immunodeficiency, bone marrow disease, or severe uncontrolled infections. Tuberculosis (TB) has been observed in clinical studies of AUBAGIO. Before starting treatment, screen patients for latent TB infection with a tuberculin test. Treatment in patients with acute or chronic infections should not be started until the infection(s) is resolved. Administration of live vaccines is not recommended. The risk of malignancy, particularly lymphoproliferative disorders, or infection may be increased with the use of some medications with immunosuppressive potential, including teriflunomide.Peripheral neuropathy, including polyneuropathy and mononeuropathy, has been reported with AUBAGIO. Age >60 years, concomitant neurotoxic medications, and diabetes may increase the risk. If peripheral neuropathy is suspected, consider discontinuing treatment and performing accelerated elimination.Interstitial lung disease and rare cases of Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with leflunomide; a similar risk would be expected for teriflunomide. If a severe skin reaction develops with AUBAGIO, stop treatment and use accelerated elimination.Blood pressure increases and hypertension have occurred with AUBAGIO. Measure blood pressure at treatment initiation and manage any elevations during treatment.

Adverse Reactions: The most frequent adverse reactions (≥10% and ≥2% greater than placebo) with AUBAGIO 7 mg and 14 mg and placebo, respectively, were headache (18% and 16% vs 15%), ALT increased (13% and 15% vs 9%), diarrhea (13% and 14% vs 8%), alopecia (10% and 13% vs 5%), and nausea (8% and 11% vs 7%).Drug Interactions: Monitor patients when teriflunomide is coadministered with warfarin, or with drugs metabolized by CYP1A2, CYP2C8, substrates of OAT3 transporters, substrates of BCRP, or OATP1B1/1B3 transporters.Use in Specific Populations: AUBAGIO is detected in human semen. To minimize any possible fetal risk, men not wishing to father a child and their female partners should use reliable contraception. Men wishing to father a child should discontinue therapy and undergo accelerated elimination, with verification of plasma concentrations <0.02 mcg/mL. Nursing mothers should not use AUBAGIO.Please see Brief Summary of Full Prescribing Information, including boxed WARNING regarding hepatotoxicity and use in pregnancy, on the following pages.

AUBAGIO® (teriflunomide) was proven again and again to reduce key measures of disease activity: sustained disability progression (14 mg only), annualized relapse rate, and MRI activity1

AUBAGIO 14 mg is the only oral MS therapy with 2 pivotal Phase III trials that show a significant reduction in the risk of sustained disability accumulation1,3,4

— AUBAGIO 7 mg did not demonstrate a significant reduction in risk of sustained disability progression in either trial1

AUBAGIO has demonstrated a consistent safety profile across 4 separate trials in 2047 patients1

One daily tablet that can be taken anytime, anyplace1

TEMSO: A double-blind, placebo-controlled trial in patients with relapsing forms of MS (N=1088). Patients were randomized to receive AUBAGIO 14 mg (n=359), AUBAGIO 7 mg (n=366), or placebo (n=363) once daily for 108 weeks.1

TOWER: A double-blind, placebo-controlled trial in patients with relapsing forms of MS (N=1169). Patients were randomized to receive AUBAGIO 14 mg (n=372), AUBAGIO 7 mg (n=408), or placebo (n=389) once daily with results for up to 40 months of treatment.1,5

TOPIC: A double-blind, placebo-controlled clinical trial in patients with relapsing MS (N=618). Patients were randomized to receive AUBAGIO 14 mg (n=216), AUBAGIO 7 mg (n=205), or placebo (n=197) once daily for 108 weeks. Patients had a first clinical event consistent with acute demyelination occurring within 90 days of randomization with 2 or more T2 lesions at least 3 mm in diameter characteristic of MS.1,6

Study 4: A randomized, double-blind, placebo-controlled trial in patients with relapsing forms of MS (N=179). Patients were randomized to receive AUBAGIO 14 mg (n=57), AUBAGIO 7 mg (n=61), or placebo (n=61) once daily for 36 weeks.1

* AUBAGIO is effective across key measures of disease activity: sustained disability progression (14 mg only), annualized relapse rate, and MRI activity. Common adverse events with AUBAGIO led to treatment discontinuation rates ≤3.3% in the pooled clinical trials.1,2

QUIETING MS

for your patients with relapsing MS

Quietly *

S:15”S:10.25”

T:15.5”T:10.75”

B:15.75”B:11”

F:7.75”

FS:7.25”

F:7.75”

FS:7.25”

GZUS.AUBA.15.03.0728_04-14244H_CMSC_Ad_188796_7v2_fnl.indd 2-3 3/18/15 12:04 PM

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GZUS.AUBA.15.03.0728_04-14244H_CMSC_Ad_188796_7v2_fnlModifi ed: March 18, 2015 11:44 AM

Bleed 8” x 11”

Trim 7.75” x 10.75”

Safety 7.25” x 10.25”

Finished 7.75” x 10.75”

References: 1. AUBAGIO® (terifl unomide) [package insert]. Cambridge, MA: Genzyme Corporation; October 2014. 2. Data on fi le, Sanofi /Genzyme. Summary of safety HMR1726-terifl unomide. July 30, 2013. 3. Tecfi dera (dimethyl fumarate) [package insert]. Cambridge, MA: Biogen Idec Inc.; March 2013. 4. Gilenya (fi ngolimod) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; April 2014. 5. Confavreux C, O’Connor P, Comi G, et al; for the TOWER Trial Group. Oral terifl unomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2014;13(3):247-256. 6. Miller AE, Wolinsky JS, Kappos L, et al; for the TOPIC Study Group. Oral terifl unomide for patients with a fi rst clinical episode suggestive of multiple sclerosis (TOPIC): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2014;13(10):977-986.

CUSTOMIZED SUPPORT FROM THE START

Help your patients manage their RMS with AUBAGIO® (terifl unomide) and MS One to One®

One step to get started: the AUBAGIO Start form is both a prescription for AUBAGIO and enrollment for support offered by MS One to One

AUBAGIO is effective across key measures of disease activity: sustained disability progression (14 mg only), annualized relapse rate, and MRI activity. Common adverse events with AUBAGIO led to treatment discontinuation rates ≤3.3% in the pooled clinical trials.1,2

Please see Important Safety Information on previous pages and Brief Summary of Full Prescribing Information, including boxed WARNING regarding hepatotoxicity and use in pregnancy, on the following pages.

©2015 Genzyme Corporation, a Sanofi company. All rights reserved. GZUS.AUBA.15.03.0728 March 2015

›

S:7.25”S:10.25”

T:7.75”T:10.75”

B:8”B:11”

GZUS.AUBA.15.03.0728_04-14244H_CMSC_Ad_188796_7v2_fnl.indd 4 3/18/15 12:04 PM

Visit us at BOOTH 101 at the 2015 CMSCmeeting in Indianapolis.

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AUBAGIO® Rx Only(teriflunomide) tablets, for oral use

Brief Summary of Prescribing Information

WARNING: HEPATOTOXICITY and RISK OF TERATOGENICITY

Hepatotoxicity

Severe liver injury including fatal liver failure has been reported inpatients treated with leflunomide, which is indicated for rheumatoidarthritis. A similar risk would be expected for teriflunomide becauserecommended doses of teriflunomide and leflunomide result in a similarrange of plasma concentrations of teriflunomide. Concomitant use ofAUBAGIO with other potentially hepatotoxic drugs may increase the riskof severe liver injury. Obtain transaminase and bilirubin levels within 6months before initiation of AUBAGIO therapy. Monitor ALT levels at leastmonthly for six months after starting AUBAGIO [see Warnings andPrecautions (5.1)]. If drug induced liver injury is suspected, discontinueAUBAGIO and start an accelerated elimination procedure withcholestyramine or charcoal [see Warnings and Precautions (5.3)].AUBAGIO is contraindicated in patients with severe hepatic impairment[see Contraindications (4.1)]. Patients with pre-existing liver disease maybe at increased risk of developing elevated serum transaminases whentaking AUBAGIO.

Risk of Teratogenicity

Based on animal data, AUBAGIO may cause major birth defects if usedduring pregnancy. Pregnancy must be excluded before startingAUBAGIO. AUBAGIO is contraindicated in pregnant women or women ofchildbearing potential who are not using reliable contraception. Preg-nancy must be avoided during AUBAGIO treatment or prior to thecompletion of an accelerated elimination procedure after AUBAGIOtreatment [see Contraindications (4.2), Warnings and Precautions (5.2),and Use in Specific Populations (8.1)].

1 INDICATIONS AND USAGEAUBAGIO® is indicated for the treatment of patients with relapsing forms of multiplesclerosis.2 DOSAGE AND ADMINISTRATIONThe recommended dose of AUBAGIO is 7 mg or 14 mg orally once daily. AUBAGIOcan be taken with or without food.Monitoring to assess safety

• Obtain transaminase and bilirubin levels within 6 months before initiation ofAUBAGIO therapy. Monitor ALT levels at least monthly for six months afterstarting AUBAGIO [see Warnings and Precautions (5.1)].

• Obtain a complete blood cell count (CBC) within 6 months before the initiationof treatment with AUBAGIO. Further monitoring should be based on signs andsymptoms of infection [see Warnings and Precautions (5.4)].

• Prior to initiating AUBAGIO, screen patients for latent tuberculosis infection witha tuberculin skin test or blood test for mycobacterium tuberculosis infection [seeWarnings and Precautions (5.4)].

• Check blood pressure before start of AUBAGIO treatment and periodicallythereafter [see Warnings and Precautions (5.7)].

4 CONTRAINDICATIONS4.1. Severe Hepatic ImpairmentPatients with severe hepatic impairment [see Warnings and Precautions (5.1)].4.2 Patients Who are Pregnant or Women of Childbearing Potential Not

Using Reliable ContraceptionAUBAGIO may cause fetal harm when administered to a pregnant woman.In animal studies, teriflunomide has been shown to be selectively teratogenic andembryolethal in multiple species when administered during pregnancy at doses lessthan those used clinically. Nonclinical studies indicate further that the intendedpharmacologic action of the drug is involved in the mechanism of developmentaltoxicity [see Use in Specific Populations (8.1)].AUBAGIO is contraindicated in women who are pregnant or women of child bearingpotential not using reliable contraception. If this drug is used during pregnancy, orif the patient becomes pregnant while taking this drug, the patient should beapprised of the potential hazard to a fetus. If pregnancy does occur during treatment,the drug should be immediately discontinued and an accelerated eliminationprocedure should be initiated [see Warnings and Precautions (5.3)]. Under theseconditions, the patient should be referred to an obstetrician/gynecologist, preferablyexperienced in reproductive toxicity, for further evaluation and counseling [seeWarnings and Precautions and Use in Specific Populations (5.2, 8.1)].4.3. Current treatment with leflunomideCo-administration of teriflunomide with leflunomide is contraindicated.5 WARNINGS AND PRECAUTIONS5.1 HepatotoxicitySevere liver injury including fatal liver failure and dysfunction has been reported insome patients treated with leflunomide, which is indicated for rheumatoid arthritis.A similar risk would be expected for teriflunomide because recommended doses ofteriflunomide and leflunomide result in a similar range of plasma concentrations ofteriflunomide. Patients with pre-existing liver disease may be at increased risk ofdeveloping elevated serum transaminases when taking AUBAGIO. Patients with

pre-existing acute or chronic liver disease, or those with serum alanine aminotrans-ferase (ALT) greater than two times the upper limit of normal (ULN) before initiatingtreatment, should not normally be treated with AUBAGIO. AUBAGIO is contraindi-cated in patients with severe hepatic impairment [see Contraindications (4.1)].In placebo-controlled trials, ALT greater than three times the ULN occurred in61/1045 (5.8%) and 62/1002 (6.2%) of patients receiving AUBAGIO 7 mg and 14mg, respectively, and 38/997 (3.8%) of patients receiving placebo, during thetreatment period. These elevations occurred mostly within the first year of treatment.Half of the cases returned to normal without drug discontinuation. In clinical trials,if ALT elevation was greater than three times the ULN on two consecutive tests,AUBAGIO was discontinued and patients underwent an accelerated eliminationprocedure [see Warnings and Precautions (5.3)]. Of the patients who underwentdiscontinuation and accelerated elimination in controlled trials, half returned tonormal or near normal values within 2 months.One patient in the controlled trials developed ALT 32 times the ULN and jaundice5 months after initiation of AUBAGIO 14 mg treatment. The patient was hospitalizedfor 5 weeks and recovered after plasmapheresis and cholestyramine acceleratedelimination procedure. AUBAGIO-induced liver injury in this patient could not beruled out.Obtain serum transaminase and bilirubin levels within 6 months before initiation ofAUBAGIO therapy. Monitor ALT levels at least monthly for six months after startingAUBAGIO. Consider additional monitoring when AUBAGIO is given with otherpotentially hepatotoxic drugs. Consider discontinuing AUBAGIO if serum transami-nase increase (greater than three times the ULN) is confirmed. Monitor serumtransaminase and bilirubin on AUBAGIO therapy, particularly in patients whodevelop symptoms suggestive of hepatic dysfunction, such as unexplained nausea,vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine. If liverinjury is suspected to be AUBAGIO-induced, discontinue AUBAGIO and start anaccelerated elimination procedure [see Warnings and Precautions (5.3)] and monitorliver tests weekly until normalized. If AUBAGIO-induced liver injury is unlikelybecause some other probable cause has been found, resumption of AUBAGIOtherapy may be considered.5.2 Use in Women of Childbearing PotentialThere are no adequate and well-controlled studies evaluating AUBAGIO in pregnantwomen. However, based on animal studies, teriflunomide may increase the risk ofteratogenic effects or fetal death when administered to a pregnant woman [seeContraindications (4.2)].Women of childbearing potential must not be started on AUBAGIO until pregnancyis excluded and it has been confirmed that they are using reliable contraception.Before starting treatment with AUBAGIO, patients must be fully counseled on thepotential for serious risk to the fetus. The patient must be advised that if there isany delay in onset of menses or any other reason to suspect pregnancy, they mustnotify the physician immediately for pregnancy testing and, if positive, the physicianand patient must discuss the risk to the fetus. It is possible that rapidly lowering theplasma concentration of teriflunomide by instituting an accelerated eliminationprocedure may decrease the risk to the fetus from AUBAGIO [see Warnings andPrecautions (5.3)].Upon discontinuing AUBAGIO, it is recommended that all women of childbearingpotential undergo an accelerated elimination procedure. Women receiving AUBA-GIO treatment who wish to become pregnant must discontinue AUBAGIO andundergo an accelerated elimination procedure, which includes verification of teri-flunomide plasma concentrations less than 0.02 mg/L (0.02 mcg/mL). Humanplasma concentrations of teriflunomide less than 0.02 mg/L (0.02 mcg/mL) areexpected to have minimal risk [see Contraindications (4.2), Warnings and Precau-tions (5.3) and Use in Specific Populations (8.1)].5.3 Procedure for Accelerated Elimination of TeriflunomideTeriflunomide is eliminated slowly from the plasma. Without an accelerated elimi-nation procedure, it takes on average 8 months to reach plasma concentrations lessthan 0.02 mg/L, although because of individual variations in drug clearance it maytake as long as 2 years. An accelerated elimination procedure could be used at anytime after discontinuation of AUBAGIO. Elimination can be accelerated by either ofthe following procedures:

• Administration of cholestyramine 8 g every 8 hours for 11 days. Ifcholestyramine 8 g three times a day is not well tolerated, cholestyramine 4 gthree times a day can be used.

• Administration of 50 g oral activated charcoal powder every 12 hours for 11days.

If either elimination procedure is poorly tolerated, treatment days do not need to beconsecutive unless there is a need to lower teriflunomide plasma concentrationrapidly.At the end of 11 days, both regimens successfully accelerated teriflunomideelimination, leading to more than 98% decrease in teriflunomide plasma concen-trations.Use of the accelerated elimination procedure may potentially result in return ofdisease activity if the patient had been responding to AUBAGIO treatment.5.4 Bone Marrow Effects/Immunosuppression Potential/InfectionsWhite Blood Cell (WBC) count decreaseA mean decrease in white blood cell (WBC) count of approximately 15% (mainlyneutrophils and lymphocytes) and in platelet count of approximately 10% wasobserved in placebo-controlled trials with 7 mg and 14 mg of AUBAGIO comparedto baseline. The decrease in mean WBC count occurred during the first 6 weeksand WBC count remained low during treatment. In placebo-controlled studies,neutrophil count < 1.5×109/L was observed in 12% and 16% of patients receivingAUBAGIO 7 mg and 14 mg, respectively, compared with 7% of patients receivingplacebo; lymphocyte count <0.8×109/L was observed in 10% and 12% of patients

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receiving AUBAGIO 7 mg and 14 mg, respectively, compared with 6% of patientsreceiving placebo. No cases of serious pancytopenia were reported in premarketingclinical trials of AUBAGIO but rare cases of pancytopenia, agranulocytosis, andthrombocytopenia have been reported in the postmarketing setting with leflunomide.A similar risk would be expected for AUBAGIO [see Clinical Pharmacology (12.3)in the full prescribing information]. Obtain a complete blood cell count (CBC) within6 months before the initiation of treatment with AUBAGIO. Further monitoring shouldbe based on signs and symptoms suggestive of bone marrow suppression.Risk of Infection / Tuberculosis ScreeningPatients with active acute or chronic infections should not start treatment until theinfection(s) is resolved. If a patient develops a serious infection consider suspendingtreatment with AUBAGIO and using an accelerated elimination procedure. Reassessthe benefits and risks prior to resumption of therapy. Instruct patients receivingAUBAGIO to report symptoms of infections to a physician.AUBAGIO is not recommended for patients with severe immunodeficiency, bonemarrow disease, or severe, uncontrolled infections. Medications like AUBAGIO thathave immunosuppression potential may cause patients to be more susceptible toinfections, including opportunistic infections.In placebo-controlled studies of AUBAGIO, no overall increase in the risk of seriousinfections was observed with AUBAGIO 7 mg (2.2%) or 14 mg (2.7%) compared toplacebo (2.2%). However, one fatal case of klebsiella pneumonia sepsis occurredin a patient taking AUBAGIO 14 mg for 1.7 years. Fatal infections have beenreported in the post-marketing setting in patients receiving leflunomide, especiallyPneumocystis jiroveci pneumonia and aspergillosis. Most of the reports wereconfounded by concomitant immunosuppressant therapy and/or comorbid illnesswhich, in addition to rheumatoid disease, may predispose patients to infection. Inclinical studies with AUBAGIO, cytomegalovirus hepatitis reactivation has beenobserved.In clinical studies with AUBAGIO, cases of tuberculosis have been observed. Priorto initiating AUBAGIO, screen patients for latent tuberculosis infection with atuberculin skin test or with a blood test for mycobacterium tuberculosis infection.AUBAGIO has not been studied in patients with a positive tuberculosis screen, andthe safety of AUBAGIO in individuals with latent tuberculosis infection is unknown.For patients testing positive in tuberculosis screening, treat by standard medicalpractice prior to therapy with AUBAGIO.VaccinationNo clinical data are available on the efficacy and safety of live vaccinations inpatients taking AUBAGIO. Vaccination with live vaccines is not recommended. Thelong half-life of AUBAGIO should be considered when contemplating administrationof a live vaccine after stopping AUBAGIO.MalignancyThe risk of malignancy, particularly lymphoproliferative disorders, is increased withthe use of some immunosuppressive medications. There is a potential for immu-nosuppression with AUBAGIO. No apparent increase in the incidence of malignan-cies and lymphoproliferative disorders was reported in the AUBAGIO clinical trials,but larger and longer-term studies would be needed to determine whether there isan increased risk of malignancy or lymphoproliferative disorders with AUBAGIO.5.5 Peripheral NeuropathyIn placebo-controlled studies, peripheral neuropathy, including both polyneuropathyand mononeuropathy (e.g., carpal tunnel syndrome), occurred more frequently inpatients taking AUBAGIO than in patients taking placebo. The incidence ofperipheral neuropathy confirmed by nerve conduction studies was 1.4% (13patients) and 1.9% (17 patients) of patients receiving 7 mg and 14 mg of AUBAGIO,respectively, compared with 0.4% receiving placebo (4 patients). Treatment wasdiscontinued in 0.7% (8 patients) with confirmed peripheral neuropathy (3 patientsreceiving AUBAGIO 7 mg and 5 patients receiving AUBAGIO 14 mg). Five of themrecovered following treatment discontinuation. Not all cases of peripheral neuropa-thy resolved with continued treatment. Peripheral neuropathy also occurred inpatients receiving leflunomide.Age older than 60 years, concomitant neurotoxic medications, and diabetes mayincrease the risk for peripheral neuropathy. If a patient taking AUBAGIO developssymptoms consistent with peripheral neuropathy, such as bilateral numbness ortingling of hands or feet, consider discontinuing AUBAGIO therapy and performingan accelerated elimination procedure [see Warnings and Precautions (5.3)].5.6 Skin ReactionsRare cases of Stevens-Johnson syndrome and toxic epidermal necrolysis havebeen reported in patients with rheumatoid arthritis receiving leflunomide. A similarrisk would be expected for AUBAGIO [see Clinical Pharmacology (12.3) in the fullprescribing information]. If a patient taking AUBAGIO develops any of theseconditions, stop AUBAGIO therapy and perform an accelerated elimination proce-dure [see Warnings and Precautions (5.3)].5.7 Increased Blood PressureIn placebo-controlled studies, the mean change from baseline to the end of studyin systolic blood pressure was +2.3 mmHg and +2.7 mmHg for AUBAGIO 7 mg and14 mg, respectively, and -0.6 mmHg for placebo. The change from baseline indiastolic blood pressure was +1.4 mmHg and +1.9 mmHg for AUBAGIO 7 mg and14 mg, respectively, and -0.3 mmHg for placebo. Hypertension was an adversereaction in 3.1% and 4.3% of patients treated with 7 mg or 14 mg of AUBAGIOcompared with 1.8% for placebo. Check blood pressure before start of AUBAGIOtreatment and periodically thereafter. Elevated blood pressure should be appropri-ately managed during treatment with AUBAGIO.5.8 Respiratory EffectsInterstitial lung disease and worsening of pre-existing interstitial lung disease havebeen reported during treatment with leflunomide. A similar risk would be expectedfor AUBAGIO [see Clinical Pharmacology (12.3) in the full prescribing information].

Interstitial lung disease may be fatal. Interstitial lung disease may occur acutely atany time during therapy and has a variable clinical presentation. New onset orworsening pulmonary symptoms, such as cough and dyspnea, with or withoutassociated fever, may be a reason for discontinuation of the therapy and for furtherinvestigation as appropriate. If discontinuation of the drug is necessary, considerinitiation of an accelerated elimination procedure [see Warnings and Precautions(5.3)].5.9 Concomitant Use with Immunosuppressive or Immunomodulating

TherapiesCo-administration with antineoplastic, or immunosuppressive therapies used fortreatment of multiple sclerosis has not been evaluated. Safety studies in whichAUBAGIO was concomitantly administered with other immune modulating therapiesfor up to one year (interferon beta, glatiramer acetate) did not reveal any specificsafety concerns. The long term safety of these combinations in the treatment ofmultiple sclerosis has not been established.In any situation in which the decision is made to switch from AUBAGIO to anotheragent with a known potential for hematologic suppression, it would be prudent tomonitor for hematologic toxicity, because there will be overlap of systemic exposureto both compounds. Use of an accelerated elimination procedure may decrease thisrisk, but may also potentially result in return of disease activity if the patient hadbeen responding to AUBAGIO treatment [see Warnings and Precautions (5.3)].6 ADVERSE REACTIONSThe following serious adverse reactions are described elsewhere in the prescribinginformation:

• Hepatotoxicity [see Contraindications (4.1) and Warnings and Precautions(5.1)]

• Bone Marrow Effects/Immunosuppression Potential/Infections [see Warningsand Precautions (5.4)]

• Peripheral Neuropathy [see Warnings and Precautions (5.5)]• Skin Reactions [see Warnings and Precautions (5.6)]• Increased Blood Pressure [see Warnings and Precautions (5.7)]• Respiratory Effects [see Warnings and Precautions (5.8)]

6.1 Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, adversereaction rates observed in the clinical trials of a drug cannot be directly comparedto rates in the clinical trials of another drug and may not reflect the rates observedin clinical practice.A total of 2047 patients receiving AUBAGIO (7 mg or 14 mg once daily) constitutedthe safety population in the pooled analysis of placebo controlled studies in patientswith relapsing forms of multiple sclerosis; of these, 71% were female. The averageage was 37 years.Table 1 lists adverse reactions in placebo-controlled trials with rates that were atleast 2% for AUBAGIO patients and also at least 2% above the rate in placebopatients. The most common were headache, an increase in ALT, diarrhea, alopecia,and nausea. The adverse reaction most commonly associated with discontinuationwas an increase in ALT (3.3%, 2.6%, and 2.3% of all patients in the AUBAGIO 7mg, AUBAGIO 14 mg, and placebo treatment arms, respectively).

Table 1. Adverse Reactions in Pooled Placebo-Controlled Studies inPatients with Relapsing Forms of Multiple Sclerosis

Adverse Reaction

AUBAGIO7 mg

(N=1045)

AUBAGIO14 mg

(N=1002)Placebo(N=997)

Headache 18% 16% 15%Increase in Alanineaminotransferase 13% 15% 9%Diarrhea 13% 14% 8%Alopecia 10% 13% 5%Nausea 8% 11% 7%Paresthesia 8% 9% 7%Arthralgia 8% 6% 5%Neutropenia 4% 6% 2%Hypertension 3% 4% 2%

Cardiovascular deathsFour cardiovascular deaths, including three sudden deaths, and one myocardialinfarction in a patient with a history of hyperlipidemia and hypertension werereported among approximately 2600 patients exposed to AUBAGIO in the premar-keting database. These cardiovascular deaths occurred during uncontrolled exten-sion studies, one to nine years after initiation of treatment. A relationship betweenAUBAGIO and cardiovascular death has not been established.Acute Renal FailureIn placebo-controlled studies, creatinine values increased more than 100% overbaseline in 8/1045 (0.8%) patients in the 7 mg AUBAGIO group and 6/1002 (0.6%)patients in the 14 mg AUBAGIO group versus 4/997 (0.4%) patients in the placebogroup. These elevations were transient. Some elevations were accompanied byhyperkalemia. AUBAGIO may cause acute uric acid nephropathy with transientacute renal failure because AUBAGIO increases renal uric acid clearance.HypophosphatemiaIn clinical trials, 18% of AUBAGIO-treated patients had hypophosphatemia withserum phosphorus levels of at least 0.6 mmol/L, compared to 7% of placebo-treated

AUBAGIO®

(teriflunomide) tablets, for oral use

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patients; 4% of AUBAGIO-treated patients had hypophosphatemia with serumphosphorus levels at least 0.3 mmol/L but less than 0.6 mmol/L, compared to 0.8%of placebo-treated patients. No patient in any treatment group had a serumphosphorus below 0.3 mmol/L.7 DRUG INTERACTIONSEffect of AUBAGIO on CYP2C8 substratesTeriflunomide is an inhibitor of CYP2C8 in vivo. In patients taking AUBAGIO,exposure of drugs metabolized by CYP2C8 (e.g., paclitaxel, pioglitazone, repaglin-ide, rosiglitazone) may be increased. Monitor these patients and adjust the dose ofthe concomitant drug(s) metabolized by CYP2C8 as required [see Clinical Phar-macology (12.3) in the full prescribing information].Effect of AUBAGIO on warfarinCoadministration of AUBAGIO with warfarin requires close monitoring of theinternational normalized ratio (INR) because AUBAGIO may decrease peak INR byapproximately 25%.Effect of AUBAGIO on oral contraceptivesAUBAGIO may increase the systemic exposures of ethinylestradiol and levonorg-estrel. Consideration should be given to the type or dose of contraceptives used incombination with AUBAGIO [see Clinical Pharmacology (12.3) in the full prescribinginformation].Effect of AUBAGIO on CYP1A2 substratesTeriflunomide may be a weak inducer of CYP1A2 in vivo. In patients takingAUBAGIO, exposure of drugs metabolized by CYP1A2 (e.g., alosetron, duloxetine,theophylline, tizanidine) may be reduced. Monitor these patients and adjust the doseof the concomitant drug(s) metabolized by CYP1A2 as required [see ClinicalPharmacology (12.3) in the full prescribing information].Effect of AUBAGIO on organic anion transporter 3 (OAT3) substratesTeriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO,exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxa-cin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be in-creased. Monitor these patients and adjust the dose of the concomitant drug(s)which are OAT3 substrates as required [see Clinical Pharmacology (12.3) in the fullprescribing information].Effect of AUBAGIO on BCRP and organic anion transporting polypeptide B1 and B3(OATP1B1/1B3) substratesTeriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patienttaking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. Forother substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g.,methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin,nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the doseof these drugs and monitor patients closely for signs and symptoms of increasedexposures to the drugs while patients are taking AUBAGIO [see Clinical Pharma-cology (12.3) in the full prescribing information].8 USE IN SPECIFIC POPULATIONS8.1 PregnancyPregnancy Category X [see Contraindications (4.2) and Warnings and Precautions(5.2)]When teriflunomide (oral doses of 1, 3, or 10 mg/kg/day) was administered topregnant rats throughout the period of organogenesis, high incidences of fetalmalformation (primarily craniofacial, and axial and appendicular skeletal defects)and embryofetal death were observed at doses not associated with maternal toxicity.Adverse effects on embryofetal development were observed following dosing atvarious stages throughout organogenesis. Maternal plasma exposure at the no-effect level (1.0 mg/kg/day) for embryofetal developmental toxicity in rats was lessthan that in humans at the maximum recommended human dose (MRHD, 14 mg/day).Administration of teriflunomide (oral doses of 1, 3.5, or 12 mg/kg/day) to pregnantrabbits throughout organogenesis resulted in high incidences of fetal malformation(primarily craniofacial, and axial and appendicular skeletal defects) and embryofetaldeath at doses associated with minimal maternal toxicity. Maternal plasma exposureat the no-effect dose (1.0 mg/kg/day) for embryofetal developmental toxicity inrabbits was less than that in humans at the MRHD.In studies in which teriflunomide (oral doses of 0.05, 0.1, 0.3, 0.6, or 1.0 mg/kg/day)was administered to rats during gestation and lactation, decreased growth, eye andskin abnormalities, and high incidences of malformation (limb defects) and postnataldeath were observed in the offspring at doses not associated with maternal toxicity.Maternal plasma exposure at the no-effect dose for pre- and postnatal develop-mental toxicity in rats (0.10 mg/kg/day) was less than that in humans at the MRHD.In animal reproduction studies of leflunomide, embryolethality and teratogeniceffects were observed in pregnant rat and rabbit at or below clinically relevantplasma teriflunomide exposures (AUC). In published reproduction studies in preg-nant mice, leflunomide was embryolethal and increased the incidence of malfor-mations (craniofacial, axial skeletal, heart and great vessel). Supplementation withexogenous uridine reduced the teratogenic effects in pregnant mice, suggesting thatthe mode of action (inhibition of mitochondrial enzyme dihydroorotate dehydroge-nase) is the same for therapeutic efficacy and developmental toxicity. At recom-mended doses in humans, teriflunomide and leflunomide result in a similar rangeof plasma concentrations of teriflunomide.Use in MalesAUBAGIO is detected in human semen. Animal studies to specifically evaluate therisk of male-mediated fetal toxicity have not been conducted. To minimize anypossible risk, men not wishing to father a child and their female partners should usereliable contraception. Men wishing to father a child should discontinue use of

AUBAGIO and undergo an accelerated elimination procedure to decrease theplasma concentration of teriflunomide to less than 0.02 mg/L (0.02 mcg/mL) [seeWarnings and Precautions (5.3)].Pregnancy RegistryAlthough AUBAGIO is contraindicated in pregnancy, a pregnancy registry has beenestablished to monitor fetal outcomes of pregnant women exposed to AUBAGIO.Physicians are encouraged to enroll pregnant women in the AUBAGIO pregnancyregistry, or pregnant women may enroll themselves, by calling 1-800-745-4447,option 2.8.3 Nursing MothersTeriflunomide was detected in rat milk following a single oral dose of teriflunomide.It is not known whether this drug is excreted in human milk. Because many drugsare excreted in human milk and because of the potential for serious adversereactions in nursing infants from AUBAGIO a decision should be made whether todiscontinue nursing or to discontinue the drug, taking into account the importanceof the drug to the mother.8.4 Pediatric UseSafety and effectiveness in pediatric patients have not been established.8.5 Geriatric UseClinical studies of AUBAGIO did not include patients over 65 years old.8.6 Hepatic ImpairmentNo dosage adjustment is necessary for patients with mild and moderate hepaticimpairment. The pharmacokinetics of teriflunomide in severe hepatic impairmenthave not been evaluated. AUBAGIO is contraindicated in patients with severehepatic impairment [see Contraindications (4.1) Warnings and Precautions (5.1),and Clinical Pharmacology (12.3) in the full prescribing information].8.7 Renal ImpairmentNo dosage adjustment is necessary for patients with mild, moderate, and severerenal impairment [see Clinical Pharmacology (12.3) in the full prescribing informa-tion].10 OVERDOSAGEThere is no experience regarding teriflunomide overdose or intoxication in humans.Teriflunomide 70 mg daily up to 14 days was well tolerated by healthy subjects.In the event of clinically significant overdose or toxicity, cholestyramine or activatedcharcoal is recommended to accelerate elimination [see Warnings and Precautions(5.3)].

Genzyme Corporation500 Kendall StreetCambridge, MA 02142A SANOFI COMPANY

October 2014a

TER-BPLR-SA-OCT14 Revised: October 2014a

AUBAGIO®

(teriflunomide) tablets, for oral use

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International Journal of MS Carexii

Kevin Alschuler, PhDUniversity of Washington School of Medicine Seattle, [email protected]

Patricia Bednarik, MS, CCC-SLP, MSCSUniversity of Pittsburgh MS CenterPittsburgh, [email protected]

Dorothea Cassidy-Pfohl, RN, BS, MSCNBala Cynwyd, [email protected]

Robert Fallis, MD, MSCSSt. Thomas Health Services Neurosciences InstituteNashville, [email protected]

Cindy Gackle, OTR/L, MSCSMinneapolis, [email protected]

Ajay Gupta, MDFort Wayne Neurological CenterFort Wayne, [email protected]

June Halper, MSN, APN-C, MSCN, FAANConsortium of MS CentersHackensack, [email protected]

Colleen Harris, MN, NP, MSCN, MSCSUniversity of Calgary MS ClinicCalgary, AB, [email protected]

Rock Heyman, MDUniversity of Pittsburgh Medical CenterPittsburgh, [email protected]

Mark Keegan, MD, FRCP(c)Mayo ClinicRochester, [email protected]

Patricia Kennedy, APN, MSCGainesville, [email protected]

Sue Kushner, MS, PTSlippery Rock UniversityValencia, [email protected]

Beverly Layton, RNBirmingham VA Medical CenterBirmingham, [email protected]

Dianne Lowden, NMSc(A), MSCNMultiple Sclerosis Research ClinicMontreal, Quebec, [email protected]

Deb Miller, PhD, LISWMellen Center for MS Treatment and ResearchCleveland, [email protected]

Becky Jo Parks, MD John L. Trotter Multiple Sclerosis CenterSt. Louis, [email protected]

Peter Riskind, MD, PhDUMASS Memorial Medical Center - MS ClinicWorcester, [email protected]

Cynthia Sullivan, PhDNeurology Center of FairfaxAnnandale, [email protected]

Gloria von Geldern, MDUniversity of Washington Medical CenterSeattle, [email protected]

Jeff Wilken, PhDNeuropsychology Associates of Fairfax, LLCFairfax, [email protected]

Roberta Winter, MSW, LCSW, MSCSRehabilitation Institute of ChicagoSkokie, [email protected]

Annette Wundes, MDWestern MS Center at UWMC/MSRRTCSeattle, [email protected]

Michael Yeung, MD, FRCPCUniversity of Calgary MS ClinicCalgary, Alberta, [email protected]

CMSC Abstract Review CommitteeMyla Goldman, MD, Co-Chair

University of Virginia Charlottesville, VA [email protected]

Amy Perrin-Ross, APN, MSN, CNRN, MSCN, Co-Chair Loyola University of Chicago MS

Chicago, IL [email protected]

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International Journal of MS Carexiii

Abstract Titles

PLATFORMSCOMPREHENSIVE CARE(CC01) Impact of Nutrition on Quality of Life, Fatigue, and

Functional Mobility in Multiple Sclerosis: A Case Series Analysis

(CC02) Day Programming for People with Multiple Sclerosis: Interdisciplinary Allied Health Perspective of Care

(CC03) The Effects of Yoga on Impairments of Body Function, Activity Limitations, and Participation Restriction for People with Multiple Sclerosis: A Review

(CC04) Experiences and Perceptions of Multiple Sclerosis and Pregnancy Among American Hispanics

(CC05) Association of Wellness Practices in Multiple Sclerosis Patients Using Self-Reported Disability Scores and MS Characteristics

(CC06) Effects of an 8-Week Self-Efficacy Plus Exercise Intervention on Physical Activity, Quality of Life, and Fatigue in an Individual with Progressive Multiple Sclerosis

COGNITION AND PSYCHOSOCIAL(CP01) Trekking Poles to Aid Multiple Sclerosis (TRAMS):

A Comparison of Psychosocial Impact and Function with Walking Assistive Devices in People with Multiple Sclerosis

(CP02) Validation of a Short Cognitive Screening Battery to Predict Fitness-to-Drive in Individuals with Multiple Sclerosis

(CP03) Modifiable Predictors of Self-Rated Cognitive Abilities in People with Multiple Sclerosis

(CP04) Cognitive Impairment in Multiple Sclerosis: A Pilot Study of the Effects of Cognitive Retraining on Quality of Life and Improvement in Cognitive Function

(CP05) A Call to Explore the Etiology of Depression Underlying the Report of Cognitive Concerns in Patients with Multiple Sclerosis

(CP06) Assessment of Information Processing Speed in Multiple Sclerosis: Past and Future

DISEASE MANAGEMENT, MECHANISMS, AND TREATMENT(DX01) The Effect of Daclizumab High-Yield Process (DAC HYP)

on Patient-Centered Functional Outcomes: Results from the DECIDE Study

(DX02) Current Marijuana Usage by Multiple Sclerosis Status and Disability in the NARCOMS Registry

(DX03) Alemtuzumab Improves Disability After Switch from Other Disease-Modifying Therapies in a High-Disability Treatment-Refractory Relapsing Multiple Sclerosis Cohort

(DX04) Disease Activity During the First Year Predicts Clinical Long-Term Outcomes in Patients with Multiple Sclerosis: Fingolimod Treatment Benefit

(DX05) Durable Effect of Alemtuzumab on MRI Activity and Brain Atrophy in Relapsing-Remitting Multiple Sclerosis Patients: 4-Year Follow-up of Care-MS II

(DX06) Increased Apolipoprotein A-I Levels Improve Clinical and Biological Markers in EAE

REHABILITATION(RH01) Effects of Maximal Strength Training on Gait and Balance in

People with Multiple Sclerosis: A Pilot Study(RH02) Impact of a Home-Based Exercise Intervention on Fitness

and Walking Outcomes in People with Multiple Sclerosis: Preliminary Results

(RH03) Utilizing Technology to Improve Patient Adherence and Professional Patient Monitoring for At-Home Exercise Programs in Patients with Multiple Sclerosis

(RH04) Mentally Simulated Motor Actions in Neurorehabilitation: A Pilot Study in Multiple Sclerosis

(RH05) Exploration of Timed Up and Go Scores With and Without a Cognitive Challenge in People with Multiple Sclerosis and a Healthy Reference Group

(RH06) Resistive Respiratory Muscle Training Increases Respiratory Muscle Strength and Exercise Endurance, and Reduces Fatigue in Multiple Sclerosis

POSTERSCOMPREHENSIVE CARE(CC07) Health-Care Reform in the United States Offers Opportunity

to the Consortium of Multiple Sclerosis Centers(CC08) New Patient Triage for Out-of-State Multiple Sclerosis

Patients(CC09) EDSS: To Walk or Not to Walk? Assessing the Reliability

of Patients to Self-Report Their Ambulation Distance Prior to Measuring Actual Distance Walked

(CC10) Role of Interdisciplinary Team in Managing Caregiver’s Stress

(CC11) Multiple Sclerosis and Adherence: A Community-Based Analysis of a Problem in MS Care

(CC12) Dysequilibrioception (Imbalance) in Multiple Sclerosis: Can Dynavision D2 Visuomotor Training System Be an Effective Tool for the Measurement of Balance?

(CC13) Best Practices in Intrathecal Baclofen Therapy: Dosing and Long-Term Management

(CC14) A Quantitative Survey of Practices in Intrathecal Baclofen Therapy

(CC15) A Qualitative Survey of Best Practices in Intrathecal Baclofen Therapy

(CC16) Patients, Partners, and Children’s Experiences Related to Need for Support and Information When a Parent Is Diagnosed with Multiple Sclerosis

(CC17) Exploring Patients’ Knowledge and Misconceptions About Multiple Sclerosis and Pregnancy

(CC18) How Well Do Neurology Residents Recognize Multiple Sclerosis? Analysis of the Close the Loop Resident Clinical Acumen Assessment Project

(CC19) Value Added: Multiple Sclerosis Nurse Certification—Real-World Implications

(CC20) Roles and Responsibilities of Nurse Practitioners and Physician Assistants in Multiple Sclerosis Care

(CC21) Providing Specialty and Primary Care to Underserved Multiple Sclerosis Patients Through a Federally Qualified Health Center (FQHC)

(CC22) NMO IgG: The Impact of the NMO Biomarker (NMO IgG) on Diagnosis and Treatment of Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorder

(CC23) Withdrawn(CC24) Audit of Multiple Sclerosis Practice Against NICE Guidelines

2014COGNITION AND PSYCHOSOCIAL(CP07) The Implementation of Emotional Support Pilot Programs for

Individuals with Multiple Sclerosis(CP08) Acute Effects of Walking, Cycling, and Yoga Exercise on

Cognition in Multiple Sclerosis(CP09) Aerobic Fitness Is Associated with Inhibitory Control in

People with Multiple Sclerosis(CP10) Behavioral Medicine in Multiple Sclerosis: What Determines

Who Receives Services?(CP11) Behavioral Medicine in Multiple Sclerosis: Exploring

Changes in Emotional and Physical Functioning(CP12) Assessment of Personality Traits, Memory, and Visual

Attention in People with Multiple Sclerosis(CP13) The Value of Clinical Screenings for Concurrent Problems

in Patients with Multiple Sclerosis Who Identify as Having Cognitive Problems

(CP14) Cognitive Evolution in Tysabri-Treated Multiple Sclerosis Patients

(CP15) Pilot Study Suggests Link Between Low Vitamin D and Executive Function in Multiple Sclerosis

(CP16) Multiple Sclerosis, Employment, Cognitive Profile, and Cognitive Testing: Predictability of SDMT and Computerized Cognitive Testing

(CP17) Differences in Functioning: Who Gets Referred to Health Psychology?

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International Journal of MS Carexiv

Abstract Titles

(TC06) Using Telehealth and Databases to Expand Multiple Sclerosis Specialty Care in the VA Health-Care System

(TC07) MS ECHO: Innovative Pilot to Improve the Capacity of Providers in Underserved Areas to Treat Multiple Sclerosis

DISEASE MANAGEMENT, MECHANISMS, AND TREATMENT(DX07) Lymphocyte Counts After Initiation of Dimethyl Fumarate(DX08) Expanding Antigen-Specific T-Regulatory Type 1 CD4+

T Cells In Vivo to Treat CNS Autoimmunity(DX09) The Safety and Efficacy of Switching from Natalizumab to

Dimethyl Fumarate: Real-World Experience(DX10) Assessing the Incidence of Elevation in Eosinophils with the

Use of Dimethyl Fumarate in Multiple Sclerosis(DX11) Lymphocyte Pharmacodynamics and Safety of Natalizumab

in Patients Previously Treated with Alemtuzumab(DX12) The Effects of Body-Mass Index on Multiple Sclerosis

Progression(DX13) Disease Activity in the First Year Predicts Clinical Outcomes

in Patients with Multiple Sclerosis in the Phase 3 FREEDOMS and FREEDOMS II Studies

(DX14) Clinical and MRI Benefits of IFNβ-1a 44 µg SC tiw Treatment over 1 Year in Patients with Relapsing Multiple Sclerosis: Subgroup Analyses of the PRISMS Study

(DX15) Disease-Modifying Therapy and the Decision-Making Process for Multiple Sclerosis Patients in NARCOMS

(DX16) Real-World Clinical Outcomes in Relapsing-Remitting Multiple Sclerosis Patients Who Switch from Natalizumab to Delayed-Release Dimethyl Fumarate

(DX17) Four-Year Expanded Disability Status Scale Outcomes in Patients Treated with Fingolimod in the Phase 3 and Extension Trial Program

(DX18) Withdrawn(DX19) Do Oral Disease-Modifying Agents Improve Adherence to

Multiple Sclerosis Treatment? A Comparison of Oral and Injectable Drugs

(DX20) A Descriptive Analysis of Time to First Treatment with Disease-Modifying Drugs in Newly Diagnosed Patients with Multiple Sclerosis

(DX21) Rate of Brain Volume Loss Under Long-Term Delayed-Release Dimethyl Fumarate Treatment in Relapsing-Remitting Multiple Sclerosis Patients: Results from the ENDORSE Study

(DX22) Resource Use, Employment Status, and Escalation to Second-Line Therapy in Patients from the BENEFIT Study 11 Years After Onset of Multiple Sclerosis Symptoms

(DX23) Consistent Efficacy of Teriflunomide in Prespecified Subgroup Analyses from a Phase 3 Trial (TOPIC) in Patients with Early Multiple Sclerosis

(DX24) An Assessment of Factors Associated with High Costs Among Patients with Multiple Sclerosis Receiving Disease-Modifying Drug Therapy

(DX25) Efficacy and Safety of Teriflunomide in Patients Switching from Other Disease-Modifying Therapies

(DX26) Clinical and MRI Efficacy of Interferon Beta-1a Subcutaneously Three Times Weekly in Multiple Sclerosis Patients with More Advanced Disease (EDSS 4.0–6.0)

(DX27) Teriflunomide Efficacy in Newly Diagnosed Patients with Relapsing Multiple Sclerosis Enrolled in the TEMSO and TOWER Studies: A Post Hoc Analysis

(DX28) 1:10,000 Is Not Zero: Lessons Learned from a Natalizumab-Related Progressive Multifocal Leukoencephalopathy Case with Repeated Negative Anti-JC Virus Antibody Testing

(DX29) Alemtuzumab Improves Sustained Accumulation of Disability Outcomes Using the SAD-Plus Assessment in Relapsing-Remitting Multiple Sclerosis Patients with Inadequate Efficacy Response to Prior Therapy

(DX30) Long-Term Efficacy and Safety of Daclizumab High-Yield Process in Relapsing-Remitting Multiple Sclerosis: Results from the SELECTED Extension Study

(DX31) Sleep Disorder in Patients with Multiple Sclerosis

(CP18) Multiple Sclerosis Care and Transgendered People: A Case Study

(CP19) Improving Fatigue and Depression in Individuals with Multiple Sclerosis Using Telephone-Administered Physical Activity Counseling

(CP20) Support Network for Young Adults with Multiple Sclerosis(CP21) The Effects of Family Functioning on Patient Self-Efficacy in

Multiple Sclerosis(CP22) Variation in the Perception of Family Function in Multiple

Sclerosis and Its Relationship with Patient Self-Efficacy(CP23) The Effects of Family Function and Disability on Perceived

Self-Efficacy in Multiple Sclerosis: Self-Efficacy Function and Self-Efficacy Control

(CP24) Appearance of Balo’s Concentric Sclerosis 18 Years After Acute Psychosis

(CP25) BICAMS Tablet Application: A Reliable and Fast Way to Assess Cognitive Functioning

(CP26) Incidence of Anxiety in Patients with Multiple SclerosisEPIDEMIOLOGY AND GENETICS(EG01) Physical Activity and the Incidence of Multiple Sclerosis(EG02) Temporal Changes in the Age at Multiple Sclerosis Onset:

Importance of Controlling for Equal Observation Time(EG03) Cohabitation Is Associated with Lower Levels of Clinical

Disability in Multiple Sclerosis(EG04) Dimethyl Fumarate–Associated Lymphopenia in Clinical

Practice: Implications for Informed Patient Management(EG05) Clinical Course of Relapsing-Remitting Multiple Sclerosis in

Nonwhite MS Patients(EG06) EDSS Pyramidal Function Score Correlations with Objective

and Subjective Measures of Ambulation(EG07) The 2D:4D Ratio, a Proxy for Prenatal Androgen Levels,

Differs in Men with Multiple Sclerosis(EG08) Vascular Comorbidities Among Patients with Multiple

Sclerosis at a Comprehensive Care Center(EG09) A Comprehensive Review of Multiple Sclerosis in IranNEUROIMAGING(NI01) Tumefactive Demyelinating Lesion of Spinal Cord Due to

Aquaporin-4 Antibody(NI02) Diffusion Tensor Imaging of the Corticospinal Tract and

Walking Outcomes in Multiple Sclerosis(NI03) Cognition and Early Thalamic Atrophy(NI04) Delayed Tumefactive Demyelination in a Patient with

Meningioma and Optic Neuritis: Case Report and Review of the Literature

BASIC SCIENCE(SC01) RGC-32, FasL, and SIRT1 as Potential Biomarkers of Relapse

and Response to Treatment with Glatiramer Acetate in Multiple Sclerosis

(SC02) Gait Termination in Individuals with Multiple Sclerosis(SC03) Falls in Older Individuals With and Without Multiple

Sclerosis(SC04) Longitudinal Study of Timed 25-Foot Walks and Retinal

Nerve Fiber Layer in a Large Multiple Sclerosis Cohort(SC05) Rocky Mountain Multiple Sclerosis Center Biorepository for

the Study of Neuroimmunologic DisorderTECHNOLOGY(TC01) Promoting Multiple Sclerosis Medication Adherence Through

Telehealth(TC02) The Use of Electronic Sleep and Symptom Diaries:

A Feasibility Study(TC03) Predisposition and Motivation Assessment in Using

Technologies in Multiple Sclerosis: A Questionnaire on a Wearable Tool for Unobtrusive Motor and Cognitive Monitoring

(TC04) Comparing the Effects of Whole-Body Vibration to Standard Exercise in Ambulatory People with Multiple Sclerosis: A Randomized Controlled Feasibility Study

(TC05) Physicochemical Characterization of Solid Lipid Nanoparticles for Dimethyl Fumarate Release

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International Journal of MS Carexv

Abstract Titles

(DX59) Effects of Peginterferon Beta-1a on Visual Dysfunction in Multiple Sclerosis

(DX60) Relapse Outcomes in Patients with Multiple Sclerosis Treated with Fingolimod After Previous Treatment with Injectable Disease-Modifying Therapies

(DX61) CPT1 Inhibitor Significantly Induces Remyelination and Neuroprotection in Multiple Sclerosis by a Dual Mode of Action

(DX62) Relapse Outcomes in Patients Treated with Fingolimod According to Disease Duration

(DX63) Effects of Monthly Pulse Methylprednisolone Therapy on Sustained Disease Progression in Secondary Progressive Multiple Sclerosis

(DX64) Tolerability Results from Year 1 of the PRISMS-2 2-Year Randomized Controlled Trial of Interferon Beta-1a SC tiw Compared with Placebo

(DX65) Patient Satisfaction with the BETACONNECT Autoinjector for Interferon Beta-1b

(DX66) Long-Term Follow-up of the Safety of Delayed-Release Dimethyl Fumarate in Relapsing-Remitting Multiple Sclerosis: Interim Results from the ENDORSE Extension Study

(DX67) Use of a Delphi Process to Gain Consensus on Effective Management of Gastrointestinal Side Effects Associated with Delayed-Release Dimethyl Fumarate

(DX68) Predictive Value of MRI Measures in Patients with Relapsing Multiple Sclerosis Receiving IFNβ-1a Subcutaneously Three Times Weekly or IFNβ-1a Intramuscularly Once Weekly: Post Hoc Analyses of Evidence Data

(DX69) Multiple Sclerosis Medication Utilization in Texas Medicaid(DX70) A Comprehensive Analysis of Relapse in Multiple Sclerosis(DX71) Patient-Reported Treatment Experience of Multiple Sclerosis

Patients Receiving Delayed-Release Dimethyl Fumarate from Specialty Pharmacy: Interim Results

(DX72) Potential Association of Aspartame with Multiple Sclerosis Relapse

(DX73) Improvements in Quality of Life Are Maintained in Alemtuzumab-Treated Relapsing-Remitting Multiple Sclerosis Patients Who Develop Autoimmune Adverse Events: CARE-MS II

(DX74) Fingolimod First-Dose Effects in the PREFERMS Real-World Study of Patients with Relapsing-Remitting Multiple Sclerosis

(DX75) Development of Chronic Black Holes Predicts Long-Term Disability: Post Hoc Analysis of Magnetic Resonance Imaging Data in the PRISMS Study

(DX76) Patient Perspectives on Insurance Changes and Therapy Decisions in NARCOMS

QUALITY OF LIFE OUTCOMES(QL01) Physical Activity, Dietary Sodium, and Smoking as

Correlates of Walking Performance in People with Multiple Sclerosis

(QL02) Baseline Characteristics of Patients Enrolled in the Teri-PRO Phase 4 Study in the United States versus Canada, Europe, and Latin America

(QL03) Impacting Lives Affected by Multiple Sclerosis: Evaluation of the National Multiple Sclerosis Society’s MS Navigator Program

(QL04) Physician Rating of Fitness-to-Drive in Multiple Sclerosis(QL05) Hair Photography Project: Exploring the Clinical Course of

Hair Thinning Associated with Teriflunomide(QL06) Tanner Health Miles: Walking and Talking Multiple Sclerosis(QL07) Association Between Measures of Disability and Employment

in Secondary Progressive Multiple Sclerosis: Baseline Data from the ASCEND Natalizumab Trial

(QL08) The Effects of Multiple Sclerosis on Daily Money Management Activities

(QL09) To What Extent Does JC Virus Status Influence Patient Decisions Regarding Treatment with Natalizumab?

(QL10) The Impact of Relapse on Productivity, Costs, and Resource Utilization in Multiple Sclerosis: A Retrospective US Database Analysis

(DX32) Baseline Demographics and Disease Characteristics from Opera Phase 3 Trials Evaluating Ocrelizumab in Patients with Relapsing Multiple Sclerosis

(DX33) Retrospective Analysis of the Treatment of Relapsing-Remitting Multiple Sclerosis with Fingolimod at the Department of Neurology, Bon Secours Hospital Tralee, Ireland

(DX34) Patient Experience and Tolerance of New Glatiramir Dosing(DX35) Evaluation of Peginterferon Beta-1a Tolerability Profile:

Gaining Consensus Using the Delphi Technique(DX36) User Trial Questionnaire and Quality of Life Responses in

Patients with Multiple Sclerosis by Neurologic and Cognitive Status: MOSAIC Study

(DX37) Safety, Tolerability, and Pharmacokinetics of ALKS 8700, a Novel Oral Therapy for Relapsing-Remitting Multiple Sclerosis, in Healthy Subjects

(DX38) The Importance of Interdisciplinary Monitoring for Disease Progression in Pediatric Multiple Sclerosis

(DX39) Infusion-Associated Reactions in Patients Receiving Alemtuzumab After Switching from Subcutaneous Interferon Beta-1a

(DX40) Effects of Fingolimod on Categorical Change in T2 Lesion Volume and Clinical Outcomes in Patients with Relapsing-Remitting Multiple Sclerosis

(DX41) Brain Volume Change by Quartile and Disability Progression in Multiple Sclerosis: A 4-Year Analysis of the Phase 3 FREEDOMS Trial and Its Extension

(DX42) Utilization and Switch Patterns with Dimethyl Fumarate in a Publicly Funded Drug Plan: The First 8 Months

(DX43) Treatment Discontinuation After Initiation of Oral Disease-Modifying Therapies in Patients with Multiple Sclerosis

(DX44) Medication Prescribing Patterns Associated with Multiple Sclerosis Patients Treated with Oral Disease-Modifying Therapies

(DX45) Predictors of Adherence Using Panel Survey Data from Multiple Sclerosis Patients Currently Treated with High-Dose, High-Frequency Interferons

(DX46) Best Practice Recommendations of Advanced Practice Clinicians for the Care of the Challenging Multiple Sclerosis Patient

(DX47) The Topographical Model of Multiple Sclerosis: A New Visualization of Disease Course

(DX48) Predictive Value of Early MRI Measures in Patients with Relapsing-Remitting Multiple Sclerosis Receiving Interferon Beta-1a SC tiw or Placebo: Post Hoc Analyses of PRISMS Data

(DX49) Dimethyl Fumarate Effects on Lymphocyte Phenotype(DX50) Investigation of the Effectiveness and Tolerability of

Colesevelam Hydrochloride for Accelerated Elimination of Teriflunomide in Healthy Subjects

(DX51) Transverse Myelitis Presenting in a Patient with Hughes-Stovin Syndrome

(DX52) Effect of Oral Fingolimod Treatment on Annualized Relapse Rates in Patients with Relapsing-Remitting Multiple Sclerosis Using Bayesian Methodology

(DX53) Analysis of the 25-Foot Timed Walk Test as a Predictive Factor in Multiple Sclerosis Disease Progression

(DX54) An Assessment of Adherence Among Multiple Sclerosis Patients Newly Initiating Treatment with a Self-Injectable versus Oral Disease-Modifying Drug

(DX55) Oligoclonal Banding Patterns in Patients with Multiple Sclerosis

(DX56) Shared Decision Making in Multiple Sclerosis: Lessons Learned from Creating New Disease-Modifying Therapy Option Grid Decision Support Tools

(DX57) Peginterferon Beta-1a and Management Strategies for Flu-Like Symptoms and Injection-Site Reactions: Obtaining Recommendations Using the Delphi Technique

(DX58) Peginterferon Beta-1a Advance Study: Subgroup Analysis over 2 Years

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International Journal of MS Carexvi

Abstract Titles

(RH28) A Clinical Pathway for the Evaluation and Treatment of Footdrop in Multiple Sclerosis

(RH29) Body Weight Supported Treadmill Training in People with Multiple Sclerosis with Mobility Limitations

(RH30) The Effects of Pericooling on Six-Minute Walk Test Performance in People with Multiple Sclerosis

(RH31) The Effects of Yoga and Meditation on Walking, Balance, and Mood in Ambulatory Multiple Sclerosis Patients

(RH32) Perceived Barriers and Facilitators for Sharing Data with an International Multiple Sclerosis Rehabilitation Repository

(RH33) Correlations Between Pyramidal and Extrapyramidal (Brainstem, Cerebellar) Functional System Disability Scores with Mobility and Strength Performance in Multiple Sclerosis

(RH34) Multiple Sclerosis Education Track Improves Self-Rated Competencies in Physical Therapy Students

SYMPTOM MANAGEMENT(SX07) Review of Pain Management in Multiple Sclerosis(SX08) Withdrawn(SX09) Gender Differences in Multiple Sclerosis–Related Pain,

Correlation with Burden of Disease(SX10) Effectiveness of Medtronic Intrathecal Drug Delivery Pump

Personal Therapy Manager in Spasticity Management(SX11) Pilot Study of a Topical Adhesive Containing Anesthetic

and Heating Components to Reduce Injection Pain with Subcutaneous Multiple Sclerosis Medications

(SX12) Effect of Dalfampridine on Subjective Domains of Functioning in Patients with Multiple Sclerosis

(SX13) Impact of Nursing Interventions on Reducing Adverse Events Related to Tecfidera

(SX14) Comorbidity Is Associated with Pain in Multiple Sclerosis(SX15) Multiple Sclerosis and Sleep Disorders: Exploration of Sleep

Latency and REM Sleep Latency in a Community Cohort of Patients with Multiple Sclerosis Who Report Fatigue

(SX16) Multiple Sclerosis and Sleep Disorders: Exploration of Sleep-Disordered Breathing–Apnea Hypopnea Index in Non-REM versus REM Sleep in Multiple Sclerosis

(SX17) “Waiting for the Science to Catch Up with the Practice”: A More Cautious Trend in Social Media Discussions of CCSVI Treatment for Multiple Sclerosis

(SX18) Social-Cognitive Determinants of Physical Activity in African Americans with Multiple Sclerosis

(SX19) Physical Activity and Exercise Training in Multiple Sclerosis: A Quality Review and Content Analysis of Perceived Determinants and Consequences

(SX20) Effects of Dalfampridine Extended Release on Motor Function in People with Multiple Sclerosis After 18 Months

(SX21) Symptom Groups Associated with Smoking Among People with Relapsing-Remitting Multiple Sclerosis

(SX22) Sleep Problems and Symptom Correlates in People with Multiple Sclerosis: A Pilot Study

(SX23) Transforming Lives: Evaluation of Immediate and 6-Month Outcomes from the Can Do Program, Can Do Multiple Sclerosis

(SX24) Qualitative Findings from a Pilot Randomized Controlled Trial of a Brief Multidisciplinary Consultation Intervention for Treating Sexual Dysfunction in Multiple Sclerosis

WHITAKER RESEARCH TRACKCapitalizing on the Interaction Between Patients and Health-Care Providers: A Qualitative Study to Explore the Exercise-Promotion Needs and Wants of Multiple Sclerosis Patients

Peak Turning Velocity as a Marker of Balance Confidence and Walking Limitation in People with Multiple Sclerosis

Evaluating Cerebellar Contributions to Physical Performance and Cognition in Multiple Sclerosis

Determining Reliable Change Using the Abbreviated Modified Fatigue Impact Scale

(QL11) Living Your Best Life with MS? Examination of the National Multiple Sclerosis Society’s Everyday Matters Program

(QL12) Withdrawn(QL13) Ballroom Dance for People with Multiple Sclerosis:

Preliminary Efficacy(QL14) A Comprehensive Revision of the Incapacity Status Scale:

ISS-2(QL15) Multiple Sclerosis in US Minorities: Results of a Research

Study Designed to Understand Educational Needs of Hispanic and African American Patients with MS

(QL16) iConquerMS: A Patient-Powered Research Network for Multiple Sclerosis

(QL17) Multiple Sclerosis Patient Adherence to Delayed-Release Dimethyl Fumarate and Patient-Reported Side Effects from a Specialty Pharmacy Program

(QL18) Connected Care for Multiple Sclerosis: Improving Adherence with Managed Therapy for Patients with Indications of Fatigue or Depression

(QL19) Perceptions About Multiple Sclerosis Among Hispanic Americans: Need for Targeted Messaging

(QL20) Mindfulness-Based Meditation for Individuals with Multiple Sclerosis in the Multiple Sclerosis Clinic

(QL21) Understanding the Needs of Hispanic/Latino Individuals and Families Affected by Multiple Sclerosis

(QL22) Employment Register of Patients on NatalizumabREHABILITATION(RH07) Functional Electrical Stimulation Cycling and Muscle

Oxidative Capacity in Two Nonambulatory People with Multiple Sclerosis

(RH08) Critical Falls Among People Aging with Multiple Sclerosis: Getting Help After a Fall

(RH09) Improving Detection of Disease Course in Multiple Sclerosis: An Alternative Patient-Reported Outcomes–Based Strategy

(RH10) Case Report: Multidisciplinary Approach to Patient with Multiple Sclerosis, with Total Dependence

(RH11) How Does Fatiguing Activity Alter Central and Peripheral Neuromotor Physiology in People with Multiple Sclerosis? A Systematic Review of the Literature

(RH12) Exploring Robotic-Assisted Locomotor Training in Physical Therapy with Multiple Sclerosis

(RH13) Fatigue Is Associated with Exercise Endurance and Quality of Life but Not Self-Reported Physical Activity in Individuals with Multiple Sclerosis

(RH14) Walking While Talking: Relationships Among Motor-Cognitive Dual-Tasks, Functional Performance, and Structural MRI

(RH15) Compliance in Rehabilitation with Multiple Sclerosis Patients(RH16) Withdrawn(RH17) Web-Based Physical Activity Resources: Listening to the

Voice of People with Multiple Sclerosis(RH18) Withdrawn(RH19) The Development of a Hand Assessment for Multiple

Sclerosis(RH20) Impairment and Disability in People with Multiple Sclerosis:

Do Functional Performance or Functional Limitations Matter?(RH21) Effects of Voluntary Exercise on the Pathogenesis of

Experimental Autoimmune Encephalomyelitis(RH22) Use of the Multiple Sclerosis Cognitive-Linguistic Checklist

and the Brief International Cognitive Assessment for Multiple Sclerosis: Generating Patient-Centered Goals

(RH23) Health Locus of Control from a Physical Perspective in Patients with Multiple Sclerosis

(RH24) Prolonged-Release Fampridine as Adjunct Therapy to Active Enabled Motor Training in Multiple Sclerosis Patients: A Pilot, Double-Blind, Placebo-Controlled Study

(RH25) Interrater Reliability of Mini-BESTest in Ambulatory People with Multiple Sclerosis

(RH26) Comparison of the Berg Balance Scale and the Mini-BESTest in Ambulatory People with Multiple Sclerosis

(RH27) Employment and Multiple Sclerosis: Recent Perspectives from Adults with MS

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Please see additional Important Safety Information and Brief Summary of full Prescribing Information, including boxed WARNING, on the following pages.

A therapy for patients with relapsing multiple sclerosis (MS)

Discover more at Booth 101

INDICATIONLEMTRADA is indicated for the treatment of patients with relapsing forms of multiple sclerosis (MS). Because of its safety profile, the use of LEMTRADA should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.

CONTRAINDICATIONSLEMTRADA is contraindicated in patients who are infected with Human Immunodeficiency Virus (HIV) because LEMTRADA causes prolonged reductions of CD4+ lymphocyte counts.

IMPORTANT SAFETY INFORMATIONWARNING: AUTOIMMUNITY, INFUSION REACTIONS, AND MALIGNANCIES

LEMTRADA causes serious, sometimes fatal, autoimmune conditions such as immune thrombocytopenia and anti-glomerular basement membrane disease. Monitor complete blood counts with differential, serum creatinine levels, and urinalysis with urine cell counts at periodic intervals for 48 months after the last dose of LEMTRADA.

LEMTRADA causes serious and life-threatening infusion reactions. LEMTRADA must be administered in a setting with appropriate equipment and personnel to manage anaphylaxis or serious infusion reactions. Monitor patients for two hours after each infusion. Make patients aware that serious infusion reactions can also occur after the 2-hour monitoring period. LEMTRADA may cause an increased risk of malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders. Perform baseline and yearly skin exams.

Because of the risk of autoimmunity, infusion reactions, and malignancies, LEMTRADA is available only through restricted distribution under a Risk Evaluation Mitigation Strategy (REMS) Program.

WARNINGS AND PRECAUTIONS• Autoimmunity: Treatment with LEMTRADA can result in the formation of autoantibodies and increase the risk of

serious autoimmune mediated conditions, and may increase the risk of other autoimmune conditions because of the broad range of autoantibody formation.

• Infusion Reactions: LEMTRADA causes cytokine release syndrome resulting in infusion reactions. In clinical studies, 92% of LEMTRADA-treated patients experienced infusion reactions. Serious reactions occurred in 3% of these patients and included anaphylaxis in 2 patients (including anaphylactic shock), angioedema, bronchospasm, hypotension, chest pain, bradycardia, tachycardia (including atrial fibrillation), transient neurologic symptoms, hypertension, headache, pyrexia, and rash. In some patients, infusion reactions were reported more than 24 hours after LEMTRADA infusion. Premedicate patients with corticosteroids immediately prior to LEMTRADA infusion for the first 3 days of each treatment course. Consider pretreatment with antihistamines and/or antipyretics. Infusion reactions may occur despite pretreatment.

04-15209_R01_LEM_US_CMSC_Abstract_Ad.indd 1 5/5/15 12:38 PM

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IMPORTANT SAFETY INFORMATION (continued)WARNINGS AND PRECAUTIONS (continued)• LEMTRADA REMS Program: Only prescribers,

patients, pharmacies and healthcare facilities certified and enrolled in the REMS program can prescribe, receive, dispense or administer LEMTRADA. Healthcare facilities must have on-site access to equipment and personnel trained to manage infusion reactions (including anaphylaxis and cardiac and respiratory emergencies).

• Immune thrombocytopenia (ITP) occurred in 2% of LEMTRADA-treated patients in clinical studies in MS. One LEMTRADA-treated patient developed ITP that went unrecognized prior to the implementation of monthly monitoring requirements, and died from an intracerebral hemorrhage. ITP has been diagnosed more than 3 years after the last LEMTRADA dose.

• Glomerular nephropathies occurred in 0.3% of LEMTRADA-treated patients in MS clinical trials and have been diagnosed up to 40 months after the last dose of LEMTRADA. There are published and post-marketing cases of MS patients treated with alemtuzumab who developed anti-glomerular basement membrane (anti-GBM) disease and subsequently developed end stage renal disease requiring renal transplantation.

• Autoimmune thyroid disorders occurred in 34% of LEMTRADA-treated patients in clinical studies. Newly diagnosed thyroid disorders occurred throughout the uncontrolled clinical study follow-up period, more than 7 years after the first LEMTRADA dose. Serious thyroid events occurred in 2% of patients. In patients with an ongoing thyroid disorder, LEMTRADA should be administered only if the potential benefit justifies the potential risks. Obtain thyroid function tests prior to initiation of treatment and every 3 months until 48 months after the last infusion. Thyroid disease poses special risks in women who are pregnant.

• Autoimmune cytopenias occurred in LEMTRADA-treated MS patients in clinical trials. One LEMTRADA-treated patient with autoimmune pancytopenia died from sepsis.

• Infections occurred in 71% of LEMTRADA-treated patients compared to 53% of patients treated with interferon beta-1a. Serious infections occurred in 3% of patients treated with LEMTRADA and 1% of patients treated with interferon beta-1a and included: appendicitis, gastroenteritis, pneumonia, herpes zoster, and tooth infection. Consider delaying LEMTRADA administration in patients with active infection until the infection is fully controlled. – Do not administer live viral vaccines following

a course of LEMTRADA, as patients may be at increased risk of infection.

– Herpes viral infection developed in 16% of LEMTRADA-treated patients compared to 3% of interferon beta-1a patients. Administer antiviral prophylaxis for herpetic viral infections starting on the first day of each treatment course and continue for a minimum of two months following treatment with LEMTRADA or until CD4+ lymphocyte count is ≥200 cells per microliter, whichever occurs later.

– Active and latent tuberculosis cases occurred in 0.3% of LEMTRADA-treated patients, most often in endemic regions.

– Before initiating LEMTRADA, consider screening patients at high risk of Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection. Carriers of HBV and/or HCV who receive LEMTRADA may be at risk of irreversible liver damage relative to a potential virus reactivation.

• Pneumonitis, including hypersensitivity pneumonitis and pneumonitis with fibrosis, occurred in 6 of 1217 (0.5%) LEMTRADA-treated patients in clinical studies. Advise patients to report symptoms of pneumonitis (e.g., shortness of breath, cough, wheezing, chest pain or tightness, and hemoptysis).

• Drug Products with Same Active Ingredient: LEMTRADA contains the same active ingredient (alemtuzumab) found in CAMPATH®. If LEMTRADA is considered for use in a patient who has previously received CAMPATH, exercise increased vigilance for additive and long-lasting effects on the immune system.

Adverse Reactions In clinical trials, the most common adverse reactions (incidence ≥10% and >interferon beta-1a) with LEMTRADA vs interferon beta-1a were: rash (53% vs 6%), headache (52% vs 23%), pyrexia (29% vs 9%), nasopharyngitis (25% vs 19%), nausea (21% vs 9%), urinary tract infection (19% vs 8%), fatigue (18% vs 13%), insomnia (16% vs 15%), upper respiratory tract infection (16% vs 13%), herpes viral infection (16% vs 3%), urticaria (16% vs 2%), pruritus (14% vs 2%), thyroid gland disorders (13% vs 3%), fungal infection (13% vs 4%), arthralgia (12% vs 9%), pain in extremity (12% vs 9%), back pain (12% vs 8%), diarrhea (12% vs 6%), sinusitis (11% vs 8%), oropharyngeal pain (11% vs 5%), paresthesia (10% vs 8%), dizziness (10% vs 5%), abdominal pain (10% vs 5%), flushing (10% vs 4%), and vomiting (10% vs 3%).Use in Specific Populations LEMTRADA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Safety and effectiveness in pediatric patients less than 17 years of age have not been established. Use of LEMTRADA is not recommended in pediatric patients due to the risks of autoimmunity and infusion reactions, and because it may increase the risk of malignancies.

LEMTRADA and Genzyme are registered trademarks of Genzyme Corporation.©2015 Genzyme Corporation, a Sanofi company. All rights reserved. GZUS.LEMT.15.02.0478a

Please see Brief Summary of full Prescribing Information, including boxed WARNING, on the following pages.


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LEMTRADA™ Rx Only(alemtuzumab) injection, for intravenous use

Brief Summary of Prescribing Information

WARNING: AUTOIMMUNITY, INFUSION REACTIONS, ANDMALIGNANCIES

• LEMTRADA causes serious, sometimes fatal, autoimmune conditionssuch as immune thrombocytopenia and anti-glomerular basementmembrane disease. Monitor complete blood counts with differential,serum creatinine levels, and urinalysis with urine cell counts atperiodic intervals for 48 months after the last dose of LEMTRADA [seeWarnings and Precautions (5.1)].

• LEMTRADA causes serious and life threatening infusion reactions.LEMTRADA must be administered in a setting with appropriate equip-ment and personnel to manage anaphylaxis or serious infusionreactions. Monitor patients for two hours after each infusion. Makepatients aware that serious infusion reactions can also occur after the2-hour monitoring period [see Warnings and Precautions (5.2)].

• LEMTRADA may cause an increased risk of malignancies, includingthyroid cancer, melanoma, and lymphoproliferative disorders. Performbaseline and yearly skin exams [see Warnings and Precautions (5.3)].

• Because of the risk of autoimmunity, infusion reactions, and malig-nancies, LEMTRADA is available only through restricted distributionunder a Risk Evaluation Mitigation Strategy (REMS) Program. Call1-855-676-6326 to enroll in the LEMTRADA REMS program [see Warn-ings and Precautions (5.4)].

1 INDICATIONS AND USAGELEMTRADA is indicated for the treatment of patients with relapsing forms of multiplesclerosis (MS). Because of its safety profile, the use of LEMTRADA should generallybe reserved for patients who have had an inadequate response to two or more drugsindicated for the treatment of MS.2 DOSAGE AND ADMINISTRATION2.1 Dosage InformationThe recommended dosage of LEMTRADA is 12 mg/day administered by intrave-nous infusion for 2 treatment courses:

• First Treatment Course: 12 mg/day on 5 consecutive days (60 mg total dose)• Second Treatment Course: 12 mg/day on 3 consecutive days (36 mg total dose)

administered 12 months after the first treatment course.2.2 VaccinationsPatients should complete any necessary immunizations at least 6 weeks prior totreatment with LEMTRADA [see Warnings and Precautions (5.9)].Prior to LEMTRADA treatment determine whether patients have a history of varicellaor have been vaccinated for varicella zoster virus (VZV). If not, test the patient forantibodies to VZV and consider vaccination for those who are antibody-negative.Postpone treatment with LEMTRADA until 6 weeks after VZV vaccination.2.3 Recommended Premedication and Concomitant MedicationCorticosteroidsPremedicate patients with high dose corticosteroids (1,000 mg methylprednisoloneor equivalent) immediately prior to LEMTRADA infusion and for the first 3 days ofeach treatment course [see Warnings and Precautions (5.2)].Herpes ProphylaxisAdminister anti-viral prophylaxis for herpetic viral infections starting on the first dayof each treatment course and continue for a minimum of two months followingtreatment with LEMTRADA or until the CD4+ lymphocyte count is ≥ 200 cells permicroliter, whichever occurs later [see Warnings and Precautions (5.9)].2.4 Preparation InstructionsFollow the steps below to prepare the diluted solution of LEMTRADA for intravenousinfusion:

• Inspect LEMTRADA visually for particulate matter and discoloration prior toadministration. Do not use if particulate matter is present or the solution isdiscolored. Do not freeze or shake vials prior to use.

• Withdraw 1.2 mL of LEMTRADA from the vial into a syringe using aseptictechnique and inject into a 100 mL bag of sterile 0.9% Sodium Chloride, USPor 5% Dextrose in Water, USP.

• Gently invert the bag to mix the solution. Ensure the sterility of the preparedsolution, because it contains no antimicrobial preservatives. Each vial is forsingle use only.

Prior to administration, protect diluted LEMTRADA solution from light and store foras long as 8 hours either at room temperature 15°C to 25°C (59°F to 77°F) or keeprefrigerated at conditions 2°C to 8°C (36°F to 46°F).2.5 Infusion InstructionsInfuse LEMTRADA over 4 hours starting within 8 hours after dilution. Extend theduration of the infusion if clinically indicated.Administer LEMTRADA in a setting in which equipment and personnel to appro-priately manage anaphylaxis or serious infusion reactions are available [seeWarnings and Precautions (5.4)].Do not add or simultaneously infuse other drug substances through the sameintravenous line. Do not administer as an intravenous push or bolus.Monitor vital signs before the infusion and periodically during the infusion. Provideappropriate symptomatic treatment for infusion reactions as needed. Considerimmediate discontinuation of the intravenous infusion if severe infusion reactionsoccur.Observe patients for infusion reactions during and for at least 2 hours after eachLEMTRADA infusion. Consider longer periods of observation if clinically indicated.

Inform patients that they should report symptoms that occur during and after eachinfusion because they may indicate a need for prompt medical intervention [seeWarnings and Precautions (5.2)].2.6 Laboratory Testing and Monitoring to Assess SafetyConduct the following laboratory tests at baseline and at periodic intervals for 48months following the last treatment course of LEMTRADA in order to monitor forearly signs of potentially serious adverse effects:

• Complete blood count (CBC) with differential (prior to treatment initiation andat monthly intervals thereafter)

• Serum creatinine levels (prior to treatment initiation and at monthly intervalsthereafter)

• Urinalysis with urine cell counts (prior to treatment initiation and at monthlyintervals thereafter)

• A test of thyroid function, such as thyroid stimulating hormone (TSH) level (priorto treatment initiation and every 3 months thereafter)

Conduct baseline and yearly skin exams to monitor for melanoma [see Warningsand Precautions (5.3)].4 CONTRAINDICATIONSLEMTRADA is contraindicated in patients who are infected with Human Immuno-deficiency Virus (HIV) because LEMTRADA causes prolonged reductions of CD4+lymphocyte counts.5 WARNINGS AND PRECAUTIONS5.1 AutoimmunityTreatment with LEMTRADA can result in the formation of autoantibodies andincrease the risk of serious autoimmune mediated conditions. In clinical studiesLEMTRADA-treated patients experienced thyroid disorders (34%), immune throm-bocytopenia (2%), and glomerular nephropathies (0.3%) [see Warnings and Pre-cautions (5.5, 5.6, 5.7)]. Autoimmune hemolytic anemia and autoimmune pancy-topenia [see Warnings and Precautions (5.8)], undifferentiated connective tissuedisorders, and acquired hemophilia A (anti-Factor VIII antibodies) each occurred in0.2% of patients. Rheumatoid arthritis, type I diabetes, vitiligo, and retinal pigmentepitheliopathy occurred in 0.1% of patients.During postmarketing use, additional autoimmune events including Guillain-Barrésyndrome and chronic inflammatory demyelinating polyradiculoneuropathy havebeen reported in the treatment of patients with B-cell chronic lymphocytic leukemia(B-CLL), as well as other disorders, generally at higher and more frequent dosesthan recommended in MS. An oncology patient treated with alemtuzumab had fataltransfusion-associated graft-versus-host disease.Autoantibodies may be transferred from the mother to the fetus during pregnancy.A case of transplacental transfer of anti-thyrotropin receptor antibodies resulting inneonatal Graves’ disease occurred after alemtuzumab treatment in the mother [seeUse in Specific Populations (8.1)].LEMTRADA may increase the risk of other autoimmune conditions because of thebroad range of autoantibody formation with LEMTRADA.Monitor complete blood counts with differential, serum creatinine levels, andurinalysis with urine cell counts before starting treatment and then at monthlyintervals for 48 months after the last dose of LEMTRADA to allow for early detectionand treatment of autoimmune adverse reactions [see Dosage and Administration(2.6)]. After 48 months, testing should be performed based on clinical findingssuggestive of autoimmunity.LEMTRADA is available only through a restricted program under a REMS [seeWarnings and Precautions (5.4)].5.2 Infusion ReactionsLEMTRADA causes cytokine release syndrome resulting in infusion reactions, someof which may be serious and life threatening. In clinical studies, 92% of LEMTRADA-treated patients experienced infusion reactions. In some patients, infusion reactionswere reported more than 24 hours after LEMTRADA infusion. Serious reactionsoccurred in 3% of patients and included anaphylaxis in 2 patients (includinganaphylactic shock), angioedema, bronchospasm, hypotension, chest pain, brady-cardia, tachycardia (including atrial fibrillation), transient neurologic symptoms,hypertension, headache, pyrexia, and rash. Other infusion reactions includednausea, urticaria, pruritus, insomnia, chills, flushing, fatigue, dyspnea, pulmonaryinfiltrates, dysgeusia, dyspepsia, dizziness, and pain. In clinical studies, 0.6% ofpatients with infusion reactions received epinephrine or atropine.During postmarketing use, other serious and sometimes fatal infusion reactionsincluded hypoxia, syncope, acute respiratory distress syndrome, respiratory arrest,myocardial infarction, acute cardiac insufficiency, and cardiac arrest have beenreported in the treatment of patients with B-CLL, as well as other disorders,generally at higher and more frequent doses than recommended in MS.Premedicate patients with corticosteroids immediately prior to LEMTRADA infusionfor the first 3 days of each treatment course. In clinical trials, patients received 1,000mg of methylprednisolone for the first 3 days of each LEMTRADA treatment course.Consider pretreatment with antihistamines and/or antipyretics prior to LEMTRADAadministration. Infusion reactions may occur despite pretreatment.Consider additional monitoring in patients with medical conditions which predisposethem to cardiovascular or pulmonary compromise.LEMTRADA can only be administered in certified healthcare settings that haveon-site access to equipment and personnel trained to manage infusion reactions(including anaphylaxis and cardiac and respiratory emergencies).LEMTRADA is available only through a restricted program under a REMS [seeWarnings and Precautions (5.4)].5.3 MalignanciesThyroid cancerLEMTRADA may increase the risk of thyroid cancer. In controlled clinical studies,3 of 919 (0.3%) LEMTRADA-treated patients developed thyroid cancer, comparedto none in the interferon beta-1a-treated group. However, screening for thyroidcancer was performed more frequently in the LEMTRADA-treated group, becauseof the higher incidence of autoimmune thyroid disorders in those patients. Twoadditional cases of thyroid cancer in LEMTRADA-treated patients occurred inuncontrolled studies.


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Patients and healthcare providers should monitor for symptoms of thyroid cancerincluding a new lump or swelling in the neck, pain in the front of the neck, persistenthoarseness or other voice changes, trouble swallowing or breathing, or a constantcough not due to an upper respiratory tract infection.MelanomaLEMTRADA may increase the risk of melanoma. In uncontrolled studies, 4 of 1486(0.3%) LEMTRADA-treated patients developed melanoma or melanoma in situ. Oneof those patients had evidence of locally advanced disease.Perform baseline and yearly skin examinations to monitor for melanoma in patientsreceiving LEMTRADA.Lymphoproliferative disorders and lymphomaCases of lymphoproliferative disorders and lymphoma have occurred inLEMTRADA-treated patients with MS, including a MALT lymphoma, Castleman’sDisease, and a fatality following treatment of non-Epstein Barr Virus-associatedBurkitt’s lymphoma. There are postmarketing reports of Epstein Barr Virus-associ-ated lymphoproliferative disorders in non-MS patients.Because LEMTRADA is an immunomodulatory therapy, caution should also beexercised in initiating LEMTRADA in patients with pre-existing or ongoing malig-nancies.LEMTRADA is available only through a restricted program under a REMS [seeWarnings and Precautions (5.4)].5.4 LEMTRADA REMS ProgramLEMTRADA is available only through a restricted program under a REMS called theLEMTRADA REMS Program, because of the risks of autoimmunity, infusionreactions, and malignancies [see Warnings and Precautions (5.1, 5.2, 5.3)].Notable requirements of the LEMTRADA REMS Program include the following:

• Prescribers must be certified with the program by enrolling and completingtraining.

• Patients must enroll in the program and comply with ongoing monitoringrequirements [see Dosage and Administration (2.6)].

• Pharmacies must be certified with the program and must only dispense tocertified healthcare facilities that are authorized to receive LEMTRADA.

• Healthcare facilities must enroll in the program and verify that patients areauthorized before infusing LEMTRADA. Healthcare facilities must have on-siteaccess to equipment and personnel trained to manage infusion reactions.

Further information, including a list of qualified healthcare facilities, is available at1-855-676-6326.5.5 Immune ThrombocytopeniaImmune thrombocytopenia (ITP) occurred in 2% of LEMTRADA-treated patients inclinical studies in MS.In a controlled clinical trial in patients with MS, one LEMTRADA-treated patientdeveloped ITP that went unrecognized prior to the implementation of monthly bloodmonitoring requirements, and died from intracerebral hemorrhage. Nadir plateletcounts ≤20,000 cells per microliter as a result of ITP occurred in 2% of allLEMTRADA-treated patients in clinical studies in MS. Anti-platelet antibodies did notprecede ITP onset. ITP has been diagnosed more than 3 years after the lastLEMTRADA dose.Symptoms of ITP include easy bruising, petechiae, spontaneous mucocutaneousbleeding (e.g., epistaxis, hemoptysis), and heavier than normal or irregular men-strual bleeding. Hemoptysis may also be indicative of anti-glomerular basementmembrane (GBM) disease [see Warnings and Precautions (5.6)], and an appro-priate differential diagnosis has to be undertaken. Remind the patient to remainvigilant for symptoms they may experience and to seek immediate medical help ifthey have any concerns.Obtain complete blood counts (CBCs) with differential prior to initiation of treatmentand at monthly intervals thereafter until 48 months after the last infusion [seeDosage and Administration (2.6)]. After this period of time, testing should beperformed based on clinical findings suggestive of ITP. If ITP is suspected, acomplete blood count should be obtained immediately. If ITP onset is confirmed,promptly initiate appropriate medical intervention.5.6 Glomerular NephropathiesGlomerular nephropathies occurred in 0.3% of LEMTRADA-treated patients in MSclinical trials. There were 3 cases of membranous glomerulonephritis and 2 casesof anti-glomerular basement membrane (anti-GBM) disease. There are publishedand post-marketing cases of MS patients treated with alemtuzumab who developedanti-GBM disease and subsequently developed end stage renal disease requiringrenal transplantation. Cases of anti-GBM disease have been diagnosed up to 40months after the last dose of LEMTRADA. Urgent evaluation and treatment isrequired because anti-GBM disease can lead to renal failure requiring dialysis ortransplantation and can be life-threatening if left untreated.Clinical manifestations of nephropathy may include elevated serum creatinine levels,hematuria, or proteinuria. Alveolar hemorrhage manifested as hemoptysis is acommon component of anti-GBM disease but did not occur in clinical trials.Obtain serum creatinine levels and urinalysis with cell counts prior to initiation oftreatment and at monthly intervals thereafter until 48 months after the last infusion.After this period of time, testing should be performed based on clinical findingssuggestive of nephropathies.If clinically significant changes from baseline in serum creatinine, unexplainedhematuria, or proteinuria are observed, perform further evaluation for nephropathies.Early detection and treatment of nephropathies may decrease the risk of pooroutcomes.5.7 Thyroid DisordersAutoimmune thyroid disorders occurred in 34% of LEMTRADA-treated patients inclinical studies. Newly diagnosed thyroid disorders occurred throughout the uncon-trolled clinical study follow-up period, more than 7 years after the first LEMTRADAdose. Autoimmune thyroid disorders included Graves’ disease, hyperthyroidism andhypothyroidism. Graves’ ophthalmopathy with decreased vision, eye pain, andexophthalmos occurred in 1% of LEMTRADA-treated patients. Two patients requiredsurgical orbital decompression. Serious thyroid events occurred in about 2% of

LEMTRADA-treated patients in clinical studies and included cardiac and psychiatricevents associated with thyroid disease. Of all LEMTRADA-treated patients, 3%underwent thyroidectomy.Thyroid disease poses special risks in women who are pregnant [see Use in SpecificPopulations (8.1)].Obtain thyroid function tests, such as TSH levels, prior to initiation of treatment andevery 3 months thereafter until 48 months after the last infusion. Continue to testthyroid function after 48 months if clinically indicated.In patients with ongoing thyroid disorder, LEMTRADA should be administered onlyif the potential benefit justifies the potential risks.5.8 Other Autoimmune CytopeniasAutoimmune cytopenias such as neutropenia (0.1%), hemolytic anemia (0.2%), andpancytopenia (0.2%) occurred in LEMTRADA-treated patients in clinical studies inMS. In cases of autoimmune hemolytic anemia, patients tested positive for directantiglobulin antibodies, and nadir hemoglobin levels ranged from 2.9-8.6 g/dL.Symptoms of autoimmune hemolytic anemia include weakness, chest pain, jaun-dice, dark urine, and tachycardia. One LEMTRADA-treated patient with autoimmunepancytopenia died from sepsis.During postmarketing use, additional autoimmune cytopenias including fatal auto-immune hemolytic anemia and aplastic anemia have been reported in the treatmentof patients with B-CLL, as well as other disorders, generally at higher and morefrequent doses than recommended in MS.Use CBC results to monitor for cytopenias. Prompt medical intervention is indicatedif a cytopenia is confirmed.5.9 InfectionsInfections occurred in 71% of LEMTRADA-treated patients compared to 53% ofpatients treated with interferon beta-1a in controlled clinical trials in MS up to 2 yearsin duration. Infections that occurred more often in LEMTRADA-treated patients thaninterferon beta-1a patients included nasopharyngitis, urinary tract infection, upperrespiratory tract infection, sinusitis, herpetic infections, influenza, and bronchitis.Serious infections occurred in 3% of patients treated with LEMTRADA as comparedto 1% of patients treated with interferon beta-1a. Serious infections in theLEMTRADA group included: appendicitis, gastroenteritis, pneumonia, herpes zoster,and tooth infection.Do not administer live viral vaccines following a course of LEMTRADA. Patientstreated with LEMTRADA have altered immunity and may be at increased risk ofinfection following administration of live viral vaccines.Consider delaying LEMTRADA administration in patients with active infection untilthe infection is fully controlled.Concomitant use of LEMTRADA with antineoplastic or immunosuppressive thera-pies could increase the risk of immunosuppression.Herpes Viral InfectionsIn controlled clinical trials, 16% of LEMTRADA-treated patients developed a herpesviral infection compared to 3% of interferon beta-1a patients. These events includedoral herpes (8.8%), herpes zoster (4.2%), herpes simplex (1.8%), and genital herpes(1.3%). Serious herpetic infections in LEMTRADA-treated patients included primaryvaricella (0.1%), herpes zoster (0.2%), and herpes meningitis (0.1%). Administerantiviral agents for herpetic prophylaxis at appropriate suppressive dosing regimens.Administer anti-viral prophylaxis for herpetic viral infections starting on the first dayof each treatment course and continue for a minimum of two months followingtreatment with LEMTRADA or until the CD4+ lymphocyte count is ≥ 200 cells permicroliter, whichever occurs later [see Dosage and Administration (2.3)].Human Papilloma VirusCervical human papilloma virus (HPV) infection, including cervical dysplasia,occurred in 2% of LEMTRADA-treated patients. Annual HPV screening is recom-mended for female patients.TuberculosisTuberculosis occurred in patients treated with LEMTRADA and interferon beta-1a incontrolled clinical trials. Active and latent tuberculosis cases occurred in 0.3% ofLEMTRADA-treated patients, most often in endemic regions. Perform tuberculosisscreening according to local guidelines prior to initiation of LEMTRADA. For patientstesting positive in tuberculosis screening, treat by standard medical practice prior totherapy with LEMTRADA.Fungal InfectionsFungal infections, especially oral and vaginal candidiasis, occurred more commonlyin LEMTRADA-treated patients (12%) than in patients treated with interferon beta-1a(3%) in controlled clinical trials in MS.Listeria InfectionsListeria meningitis has been reported in LEMTRADA-treated patients. Cases oflisteria meningitis occurred within 1 month of alemtuzumab dosing. The duration ofincreased risk for listeria meningitis is unclear. Patients should avoid or adequatelyheat foods that are potential sources of Listeria monocytogenes.Infections in non-MS patientsDuring postmarketing use, serious and sometimes fatal viral, bacterial, protozoan,and fungal infections, including some due to reactivation of latent infections, havebeen reported in the treatment of patients with B-CLL, as well as other disorders,generally at higher and more frequent doses than recommended in MS.HepatitisNo data are available on the association of LEMTRADA with Hepatitis B virus (HBV)or Hepatitis C virus (HCV) reactivation because patients with evidence of active orchronic infections were excluded from the clinical trials. Consider screening patientsat high risk of HBV and/or HCV infection before initiation of LEMTRADA andexercise caution in prescribing LEMTRADA to patients identified as carriers of HBVand/or HCV as these patients may be at risk of irreversible liver damage relative toa potential virus reactivation as a consequence of their pre-existing status.

LEMTRADA™(alemtuzumab) injection, for intravenous use


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5.10 PneumonitisIn clinical studies, 6 of 1217 (0.5%) LEMTRADA-treated patients had pneumonitisof varying severity. Cases of hypersensitivity pneumonitis and pneumonitis withfibrosis occurred in clinical studies. Patients should be advised to report symptomsof pneumonitis, which include shortness of breath, cough, wheezing, chest pain ortightness, and hemoptysis.5.11 Drug Products with Same Active IngredientLEMTRADA contains the same active ingredient (alemtuzumab) found inCAMPATH®. If LEMTRADA is considered for use in a patient who has previouslyreceived CAMPATH, exercise increased vigilance for additive and long-lastingeffects on the immune system.6 ADVERSE REACTIONSThe following serious adverse reactions are described below and elsewhere in thelabeling:

• Autoimmunity [see Boxed Warning and Warnings and Precautions (5.1)]• Infusion reactions [see Boxed Warning and Warnings and Precautions (5.2)]• Malignancies [see Warnings and Precautions (5.3)]• Immune Thrombocytopenia [see Warnings and Precautions (5.5)]• Glomerular Nephropathies [see Warnings and Precautions (5.6)]• Thyroid Disorder [see Warnings and Precautions (5.7)]• Other Autoimmune Cytopenias [see Warnings and Precautions (5.8)]• Infections [see Warnings and Precautions (5.9)]• Pneumonitis [see Warnings and Precautions (5.10)]

6.1 Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, adversereaction rates observed in the clinical trials of a drug cannot be directly comparedto rates in the clinical trials of another drug and may not reflect the rates observedin practice.In controlled clinical trials (Study 1 and Study 2), a total of 811 patients with relapsingforms of MS received LEMTRADA. A total of 811 patients received 1 course oftherapy, and 789 patients received a second course of therapy at 12 months. Theoverall follow-up in the controlled trials was equivalent to 1622 patient years, withan additional 3411 person-years of follow-up in an open label extension study. Thepopulation was 18-55 years of age, 65% were female, and 92% were Caucasian.Most Common Adverse ReactionsIn clinical trials, the most common adverse reactions with LEMTRADA (in at least10% of patients and more frequently than in interferon beta-1a) were rash,headache, pyrexia, nasopharyngitis, nausea, urinary tract infection, fatigue, insom-nia, upper respiratory tract infection, herpes viral infection, urticaria, pruritus, thyroidgland disorders, fungal infection, arthralgia, pain in extremity, back pain, diarrhea,sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, andvomiting.Table 1 lists adverse reactions occurring in ≥5% of LEMTRADA-treated patients inStudy 1 and 2 and at the same or at a higher rate than interferon beta-1a.

Table 1: Adverse Reactions in the Pooled 2-Year Active-ControlledStudies in Patients with Relapsing-Remitting Multiple Sclerosis

LEMTRADA(N=811)

%

interferon beta-1a 44mcg

(N=389)%

Rash 53 6

Headache 52 23

Pyrexia 29 9

Nasopharyngitis 25 19

Nausea 21 9

Urinary tract infection 19 8

Fatigue 18 13

Insomnia 16 15

Upper respiratory tractinfection 16 13

Herpes viral infection 16 3

Urticaria 16 2

Pruritus 14 2

Thyroid gland disorders 13 3

Fungal infection 13 4

Arthralgia 12 9

Pain in extremity 12 9

Back pain 12 8

Diarrhea 12 6

Sinusitis 11 8

Oropharyngeal pain 11 5

Paresthesia 10 8

Dizziness 10 5

Table 1: Adverse Reactions in the Pooled 2-Year Active-ControlledStudies in Patients with Relapsing-Remitting Multiple Sclerosis

(continued)

LEMTRADA(N=811)

%

interferon beta-1a 44mcg

(N=389)%

Abdominal pain 10 5

Flushing 10 4

Vomiting 10 3

Cough 9 4

Chills 9 3

Dysgeusia 8 7

Influenza 8 6

Dermatitis 8 5

Dyspepsia 8 4

Blood in urine 8 3

Dyspnea 8 1

Tachycardia 8 1

Anxiety 7 6

Muscular weakness 7 6

Bronchitis 7 4

Chest discomfort 7 2

Muscle spasms 6 5

Myalgia 6 5

Decrease in CD4lymphocytes 6 2

Decrease in CD8lymphocytes 6 2

Asthenia 5 4

Decrease in T-lymphocytecount 5 3

Erythema 5 2

Peripheral edema 5 2

Epistaxis 5 2

Neck Pain 5 2

Abnormal uterine bleeding 5 1

6.2 LymphopeniaNearly all (99.9%) patients treated with LEMTRADA in MS clinical trials experiencedlymphopenia. The lowest lymphocyte counts occurred approximately by 1 monthafter each course of treatment. The mean lymphocyte count at 1 month afterLEMTRADA treatment was 0.25 × 109L (range 0.02-2.30 × 109L) and 0.32(0.02-1.81 × 109L) for treatment courses 1 and 2, respectively. Total lymphocytecounts increased to reach the lower limit of normal in approximately 40% of patientsby 6 months after each LEMTRADA treatment course and approximately 80% ofpatients by 12 months after each course [see Clinical Pharmacology (12.2) in thefull prescribing information].6.3 Suicidal Behavior or IdeationIn clinical studies, 0.6% of patients in both the LEMTRADA and interferon beta-1agroups had events of attempted suicide or suicidal ideation. There were nocompleted suicides in either clinical study treatment group. Suicidal behavior orideation occurred in patients with or without a history of a psychiatric or thyroiddisorder. Advise patients to report immediately any symptoms of depression orsuicidal ideation to the prescribing physician.6.4 ImmunogenicityAs with all therapeutic proteins, there is potential for immunogenicity. Using anenzyme-linked immunosorbent assay (ELISA) and a competitive binding assay,anti-alemtuzumab binding antibodies were detected in 62%, 67%, and 29% ofLEMTRADA-treated patients, at months 1, 3, 12 (Course 1) as well as 83%, 83%,and 75% of LEMTRADA-treated patients at months 13, 15, and 24 (Course 2).Samples that tested positive for binding antibodies were further evaluated forevidence of in vitro inhibition using a flow cytometry assay. Neutralizing antibodieswere detected in 87%, 46%, and 5% of positive binding antibody patients at months1, 3, 12 (Course 1) as well as 94%, 88%, and 42% of positive binding antibodypatients at months 13, 15, and 24 (Course 2). Anti-alemtuzumab antibodies wereassociated with decreased alemtuzumab concentration during Course 2 but notCourse 1. There was no evidence from clinical trials that the presence of bindingor inhibitory anti-alemtuzumab antibodies had a significant effect on clinical out-comes, total lymphocyte count, or adverse events.



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The incidence of antibodies is highly dependent on the sensitivity and specificity ofthe assay. Additionally, the observed incidence of antibody (including inhibitoryantibody) positivity in an assay may be influenced by several factors including assaymethodology, sample handling, timing of sample collection, concomitant medica-tions, and underlying disease. For these reasons, comparison of the incidence ofantibodies to LEMTRADA with the incidence of antibodies to other products may bemisleading.6.5 Postmarketing ExperienceThe following adverse reactions, not described elsewhere, were identified duringpost-approval use of alemtuzumab (CAMPATH) for the treatment of B-cell chroniclymphocytic leukemia (B-CLL), as well as for the treatment of other disorders,generally at higher and more frequent doses (e.g., 30 mg) than that recommendedin the treatment of MS. Because these reactions are reported voluntarily from apopulation of uncertain size, it is not always possible to reliably estimate theirfrequency or establish a causal relationship to drug exposure.Cardiac DisordersCongestive heart failure, cardiomyopathy, and decreased ejection fraction innon-MS patients previously treated with potentially cardiotoxic agents.8 USE IN SPECIFIC POPULATIONS8.1 PregnancyPregnancy Category CThere are no adequate and well-controlled studies in pregnant women. LEMTRADAwas embryolethal in pregnant huCD52 transgenic mice when administered duringorganogenesis. Auto-antibodies may develop after administration of LEMTRADA.Placental transfer of anti-thyroid antibodies resulting in neonatal Graves’ diseasehas been reported. LEMTRADA should be used during pregnancy only if thepotential benefit justifies the potential risk to the fetus.Animal DataWhen LEMTRADA was administered to pregnant huCD52 transgenic mice duringorganogenesis (gestation days [GD] 6-10 or GD 11-15) at doses of 3 or 10 mg/kgIV, no teratogenic effects were observed. However, there was an increase inembryolethality (increased post-implantation loss and the number of dams with allfetuses dead or resorbed) in pregnant animals dosed during GD 11-15.In a separate study in pregnant huCD52 transgenic mice, administration ofLEMTRADA during organogenesis (GD 6-10 or GD 11-15) at doses of 3 or 10mg/kg/IV, decreases in B lymphocytes and T-lymphocyte populations were observedin the offspring at both doses tested. The effects of LEMTRADA, administered duringorganogenesis, on postnatal development have not been adequately assessed.Clinical ConsiderationsTo avoid in utero exposure to LEMTRADA, women of child bearing potential shoulduse effective contraceptive measures when receiving a course of treatment withLEMTRADA and for 4 months following that course of treatment.LEMTRADA induces persistent thyroid disorders [see Warnings and Precautions(5.7)]. Untreated hypothyroidism in pregnant women increases the risk for miscar-riage and may have effects on the fetus including mental retardation and dwarfism.In mothers with Graves’ disease, maternal thyroid stimulating hormone receptorantibodies can be transferred to a developing fetus and can cause neonatal Graves’disease. In a patient who developed Graves’ disease after treatment withalemtuzumab, placental transfer of anti-thyrotropin receptor antibodies resulted inneonatal Graves’ Disease with thyroid storm in her infant who was born 1 year afteralemtuzumab dosing [see Warnings and Precautions (5.1)].8.3 Nursing MothersAlemtuzumab was detected in the milk of lactating mice administered 10 mg/kgLEMTRADA on Days 8 through 12 postpartum. Serum levels of alemtuzumab weresimilar in lactating mice and offspring on Day 13 postpartum, and were associatedwith evidence of pharmacological activity (decrease in lymphocyte counts) in theoffspring.It is not known whether alemtuzumab is excreted in human milk. Because manydrugs are excreted in human milk, and because of the potential for serious adversereactions in nursing infants from LEMTRADA, a decision should be made whetherto discontinue nursing or to discontinue the drug, taking into account the importanceof the drug to the mother.8.4 Pediatric UseSafety and effectiveness in pediatric patients less than 17 years of age have notbeen established. Use of LEMTRADA is not recommended in pediatric patients dueto the risks of autoimmunity, infusion reactions, and because it may increase the riskof malignancies (thyroid, melanoma, lymphoproliferative disorders, and lymphoma)[see Warnings and Precautions (5.1, 5.2, 5.3)].8.5 Geriatric UseClinical studies of LEMTRADA did not include sufficient numbers of patients aged65 and over to determine whether they respond differently than younger patients.10 OVERDOSAGETwo MS patients experienced serious reactions (headache, rash, and eitherhypotension or sinus tachycardia) after a single accidental infusion up to 60 mg ofLEMTRADA. Doses of LEMTRADA greater than those recommended may increasethe intensity and/or duration of infusion reactions or its immune effects. There is noknown antidote for alemtuzumab overdosage.17 PATIENT COUNSELING INFORMATIONAdvise the patient to read the FDA-approved patient labeling (Medication Guide).Autoimmunity

• Advise patients to contact their healthcare provider promptly if they experienceany symptoms of potential autoimmune disease. Give examples of importantsymptoms such as bleeding, easy bruising, petechiae, purpura, hematuria,edema, jaundice, or hemoptysis [see Warnings and Precautions (5.1)].

• Advise patients of the importance of monthly blood and urine tests for 48months following the last course of LEMTRADA to monitor for signs ofautoimmunity because early detection and prompt treatment can help prevent

serious and potentially fatal outcomes associated with these events. Advisepatients that monitoring may need to continue past 48 months if they have signsor symptoms of autoimmunity.

• Advise patients that LEMTRADA may cause hyperthyroid or hypothyroiddisorders.

• Advise patients to contact their healthcare provider if they experience symp-toms reflective of a potential thyroid disorder such as unexplained weight lossor gain, fast heartbeat or palpitations, eye swelling, constipation, or feeling cold.

• Advise women of childbearing potential of the risks of pregnancy with con-comitant thyroid disease. Advise women of childbearing potential to discusspregnancy planning with their doctor.

Infusion Reactions• Advise patients that infusion reactions can occur after they leave the infusion

center [see Warnings and Precautions (5.2)].• Instruct the patient to remain at the infusion center for 2 hours after each

LEMTRADA infusion, or longer at the discretion of the physician. Advisepatients that symptoms of infusion reactions may occur after they leave theinfusion center and to report these symptoms to their doctor.

• Advise patients to contact their healthcare provider promptly if they experienceinfusion reactions, which include swelling in the mouth or throat, difficultybreathing, weakness, abnormal heart rate (fast, slow, or irregular), chest pain,and rash.

Malignancies• Advise patients that LEMTRADA may increase their risk of malignancies

including thyroid cancer and melanoma [see Warnings and Precautions (5.3)].• Advise patients to report symptoms of thyroid cancer, including a new lump or

swelling in the neck, pain in the front of the neck, hoarseness or other voicechanges that do not go away, trouble swallowing or breathing, or a constantcough not due to a cold.

• Advise patients that they should have baseline and yearly skin examinations.LEMTRADA REMS Program

• LEMTRADA is available only through a restricted program called theLEMTRADA REMS Program [see Warnings and Precautions (5.4)]. Inform thepatient of the following notable requirements:

„ Patients and providers must be enrolled in the program.„ Patients must comply with the ongoing monitoring requirements.„ Patients must report any side effects or symptoms to their doctor.

• LEMTRADA is available only at certified infusion centers participating in theprogram. Therefore, provide patients with information on the LEMTRADAREMS Program in order to locate an infusion center.

• Advise patients to read the LEMTRADA REMS material for patients, What YouNeed to Know About LEMTRADA Treatment: A Patient Guide and What YouNeed to Know About LEMTRADA Treatment and Infusion Reactions: A PatientGuide.

• Instruct patients to carry the LEMTRADA REMS Patient Safety InformationCard with them in case of an emergency.

Infections• Advise patients to contact their healthcare provider if they develop symptoms

of serious infection such as fever or swollen glands [see Warnings andPrecautions (5.9)].

• Advise patients to complete any necessary immunizations at least 6 weeks priorto treatment with LEMTRADA [see Dosage and Administration (2.2)]. Advisepatients that they should talk to their healthcare provider before taking anyvaccine after recent treatment with LEMTRADA [see Warnings and Precautions(5.9)].

• Advise patients to take their prescribed medication for herpes prophylaxis asdirected by their healthcare provider [see Warnings and Precautions (5.9)].

• Advise patients that yearly HPV screening is recommended [see Warnings andPrecautions (5.9)].

• Advise patients to avoid or adequately heat foods that are potential sources ofListeria monocytogenes if they have had a recent course of LEMTRADA. Theduration of increased risk for listeria infection after LEMTRADA administrationis not known [see Warnings and Precautions (5.9)].

Pneumonitis• Advise patients that pneumonitis has been reported in patients treated with

LEMTRADA [see Warnings and Precautions (5.10)]. Advise patients to reportsymptoms of lung disease such as shortness of breath, cough, wheezing, chestpain or tightness, and hemoptysis.

Concomitant Use of Campath• Advise patients that alemtuzumab is the same drug as Campath for use in

B-CLL. Patients should inform their healthcare provider if they have takenCampath [see Warnings and Precautions (5.11)].

Manufactured and distributed by:

Genzyme Corporation500 Kendall StreetCambridge, MA 02142

US License Number: 1596

LEMTRADA is a trademark of Genzyme Corporation.

CAMPATH is a registered trademark of Genzyme Corporation.

© 2014 Genzyme Corporation.

ALE-BPLR-PCI-AS-NOV14 Revised: November 2014



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Platforms

PLATFORMS

COMPREHENSIVE CARE

(CC01) IMPACT OF NUTRITION ON QUALITY OF LIFE, FATIGUE, AND FUNCTIONAL MOBILITY IN MULTIPLE SCLEROSIS: A CASE SERIES ANALYSISLacey Bromley,1 Susan E. Bennett1,2

1Department of Rehabilitation Science, University at Buffalo, SUNY, Buffalo, NY; 2Department of Neurology, University at Buffalo, SUNY, Buffalo, NY

Background: Multiple sclerosis (MS), an immune-modulated dis-ease, can lead to functional disability, fatigue, and decreased quality of life. Since disease-modifying therapies to control the progression of MS are only moderately efficacious and have multiple side effects, many patients seek alternative therapies. Dietary intervention is one of the alternative therapies proposed to have an effect on both etiology and progression. The process by which nutrients influence cell metabolism and inflammation in MS has been established on the molecular level; however, studies examining the role of nutrition in MS are lacking. Anti-inflammatory diets, emphasizing plant-based nutrition, high in omega-3 fats, vegetables, fruits, beans, and legumes, have been used to decrease the effects of inflammation in a variety of other disease states. These diets avoid many trademarks of the “American diet,” which is high in beef, eggs, and dairy as well as omega-6 fatty acid found in processed foods. The Therapeutic Life-style Change (TLC), created by the National Institutes of Health, is a dietary guideline that emphasizes reducing dietary cholesterol, total fat, saturated fat, and trans fats. Complementing the diet with soluble fibers and fish while monitoring sodium intake is also suggested in the TLC protocol. The TLC diet has many components of an anti-inflammatory diet and has been shown to enhance T cell–mediated immune functions. Objectives: To assess the change of self-reported measures of quality of life, fatigue, and functional mobility in a group of subjects living with MS who follow the TLC diet. Methods: This is a case series of 6 subjects living with MS over the age of 20 years with an Expanded Disability Status Scale (EDSS) score between 2.0 and 6.5. Education regarding the TLC diet and sample menus are provided to each subject. Diet is monitored over 3 months using computer-based dietary logs and assessed using 3-day food diaries and the MEDFICTS questionnaire, which is 87.5% sensitive in iden-tifying adherence to the TLC diet. Primary outcome measures include the Modified Fatigue Impact Scale, 12-item Multiple Sclerosis Walk-ing Scale, and Short Form Health Status Survey, which are assessed at baseline and at 4, 8, and 12 weeks. Results: This is an ongoing study; preliminary results will be reported at the conference. Con-clusions: It is anticipated that changes in fatigue and components of functional mobility will be observed with the dietary intervention, establishing the need for randomized controlled studies.

Supported by: NoneDisclosure: Lacey Bromley: Acorda Therapeutics (fees for non-CME services from commercial interests or their agents, grant/research support). Susan E. Ben-nett: Acorda Therapeutics (fees for non-CME services from commercial interests or their agents, grant/research support); Acorda Therapeutics, Genzyme, Medtronic (consulting fees).Keywords: Complementary/alternative therapies in MS, Comprehensive care and MS, Nutrition

(CC02) DAY PROGRAMMING FOR PEOPLE WITH MULTIPLE SCLEROSIS: INTERDISCIPLINARY ALLIED HEALTH PERSPECTIVE OF CARERebecca M. Anderson, Heidi Elm, Sue Jerve

University of Minnesota Health Fairview Achievement Center, St. Paul, MN

Background: The University of Minnesota Health Fairview Achieve-ment Center offers an integrated interdisciplinary approach to mul-tiple sclerosis (MS) in an outpatient setting. The center operates like an adult day center but is focused to meet the needs of clients with

neurodegenerative diseases to continue living at home and maintain a high quality of life. A team of social work, physical therapy, occu-pational therapy, nursing, and chaplaincy run the programming at the center. The day is structured to include physical activity, cognitive exercise, spiritual wellness, and therapeutic creative arts. The center offers a model that facilitates vital socialization to clients who would otherwise be isolated in their homes with little interaction and offers respite for caregivers. Occupational therapy and physical therapy are housed in the same building, allowing for regular follow-up with the clients during and following active treatment periods. Clients will have several episodes of care for therapy a year and then graduate on to regular maintenance programs performed by rehabilitation aides on a weekly basis to ensure therapy recommendations are being followed. Wheelchair clinics are also housed in the building to allow for regular adjustments and modifications to manual or power mobility. Of the 120 clients who attend the center in a week, 90% of them will use some type of mobility device that will need regular therapy evaluation and maintenance. The social worker is an essen-tial piece of the team to protect clients’ rights and perform regular checks that the home situation is stable. Grief and loss processing are just part of the essential areas that the chaplain will facilitate. Together, these allied health professions are creating an innovative model environment for a person with MS who finds himself or herself isolated in the home. The benefits of quality of life for patients are just starting to be evaluated in conjunction with data collected by the National Multiple Sclerosis Society and Adult Day Association. There is a qualitative effect that is easily seen by the clients, families, and employees of the center that will hopefully be confirmed with qualita-tive measures in the future. The panel will discuss the vital role each profession plays in chronic care management for people with MS in a community-based setting and how third-party payers work in this system.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Comprehensive care and MS, Management of activities of daily living in MS, MS and the caregiver/family

(CC03) THE EFFECTS OF YOGA ON IMPAIRMENTS OF BODY FUNCTION, ACTIVITY LIMITATIONS, AND PARTICIPATION RESTRICTION FOR PEOPLE WITH MULTIPLE SCLEROSIS: A REVIEWBlathin Casey, Sara Hayes, Susan B. Coote

Clinical Therapies Department, University of Limerick, Limerick, Ireland

Background: A growing body of evidence suggests positive effects for physical activity and structured exercise for people with multiple sclerosis (MS). Yoga is a form of structured exercise that is popular among people with MS. The maintenance of static and dynamic postures in yoga may enhance flexibility, balance, and strength. Relaxation and breathing control may also influence mood and sleep. Objectives: This review aims to examine the effects of yoga on impairments of body function and structure, activity limita-tions, and participation restrictions in people with MS. It will also assess the quality of research in this area. Methods: A systematic review of the literature was conducted. Searches were carried out in AMED, Web of Science, Sports Discus, Psych Articles, CINAHL, and MEDLINE. Quality was assessed using the PEDRO scale and the Cochrane risk of bias tool. Studies were included if they were a ran-domized controlled trial (RCT), there was a yoga intervention group, and all participants had a definite diagnosis of MS. Trials that were not published in English were excluded. Results: Seven RCTs with sample sizes ranging from 11 to 77 were included in this review. Participants generally had Expanded Disability Status Scale (EDSS) scores of ≤6.5; however, the majority of participants had EDSS ≤4. Outcome measures varied across the included studies. Within the domain of body function, statistically greater effects than no interven-tion were found for balance, pain, anxiety, and depression. Limita-

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perceived disability level may determine the use of wellness practic-es. Correlation between self-reported data and wellness practices has not been reported to date. Objectives: Our study intends to find a relationship between wellness practices, self-reported disability, disease duration, age, and gender in MS patients. We hypothesize that MS patients with longer disease duration and high self-reported disability scores tend to utilize a wider variety of wellness practices. Methods: MS patients were given a survey about their wellness practices. The variables of interest include exercise, weight, supple-ments, nutritional practices, and stress management techniques. Charts were reviewed for age, gender, disease duration (dd), and MSPS. The MSPS is a self-reported scale of perceived disability. Sta-tistical analysis was conducted on the data. Results: 122 surveys were completed, 80% female. The range for age was 21 to 80, with a median of 52 years; MSPS score was 0 to 36, with a median of 11.5; and dd was 1 to 43, with a median of 11 years. Exercise frequency correlated neither with MSPS (rho = 0.044, P value = .693) nor with dd (rho = 0.026, P value = .816). Patients exercised about 11 to 20 times per month, and this did not change with age. A weak correlation was observed between dd and MSPS (rho = 0.267, P value = .006). The mean, median, and standard deviations that compare the different nutritional practices to the MSPS score and dd are similar. 72% tried a nutritional wellness tool, with healthy diet being preferred. Stress management tools were used by 76%, and use increased with age and differed by sex. Supplements were used in 39%, and use was similar between sexes and was more common with increased age. Conclusions: Wellness practice use did not correlate with MSPS or disease duration, although a weak correla-tion between MSPS and disease duration was observed. The vari-ability of wellness practices increased with age. The majority of MS patients use nutrition, stress management, and exercise as wellness tools. MS caregivers should be aware that use of wellness practices by MS patients is unpredictable by age, self-reports of disability, or disease duration. This study is limited by small sample size.

Supported by: NoneDisclosure: Mary R. Rensel: Biogen, Genzyme, Novartis (consulting fees). Youran Fan: Nothing to disclose.Keywords: Complementary/alternative therapies in MS, Comprehensive care and MS, Wellness

(CC06) EFFECTS OF AN 8-WEEK SELF-EFFICACY PLUS EXERCISE INTERVENTION ON PHYSICAL ACTIVITY, QUALITY OF LIFE, AND FATIGUE IN AN INDIVIDUAL WITH PROGRESSIVE MULTIPLE SCLEROSISHeather L. Eustis, Prudence Plummer

Allied Health Sciences, The University of North Carolina, Chapel Hill, NC

Background: Increasing self-efficacy to exercise and minimizing disease-related barriers have been shown to improve physical activity levels and quality of life (QOL) in people with multiple sclerosis (MS). Currently, little research has examined exercise self-efficacy in people with more advanced MS. Objectives: To analyze the effects of a self-efficacy plus exercise intervention on physical activity endurance, QOL, fatigue, and physical activity level in a middle-aged individual with advanced MS and low self-reported self-efficacy. Methods: One 60-year-old, severely disabled female with secondary progres-sive MS participated in an 8-week intervention consisting of weekly discussions and MS-related educational presentations; four one-on-one sessions with an MS “mentor,” and daily documentation in a journal to record sleep quality, fatigue level, and physical activity. Outcome measures included a modified 5-meter walk test (5MWT), MS Impact Scale (MSIS-29), Exercise Self-Efficacy Scale (ESES), Modified Fatigue Impact Scale (MFIS), MS Self-Efficacy Scale (MS-SES), Patient Health Questionnaire-9 (PHQ-9), and daily physical activity monitoring using an accelerometer. Outcomes were assessed at baseline (week 0), postintervention (week 8), and 2 months post-intervention (week 16). The participant’s current exercise routine was modified to maximize adherence. A semistructured interview

tions in activities, namely walking endurance and speed, were simi-larly shown to improve more in the yoga groups. Positive results were found for participation with regard to reduced fatigue impact and improved quality of life. The included studies exhibited moderate-high bias with an average PEDRO score of 4.3. No adverse effects were reported in any of the included RCTs. Conclusions: Yoga has a positive effect on body function, activity limitations, and participation. However, because of the poor methodological quality of the included studies, further robust trials are required to confirm these findings. The lack of adverse events in any of the trials suggests that yoga is a safe option for people with MS. Further studies of those with greater mobility limitations are needed.

Supported by: MS Ireland through the Ireland FundDisclosure: Blathin Casey: MS Ireland (grant/research support). Sara Hayes: Health Research Board (grant/research support). Susan B. Coote: Nothing to disclose.Keywords: Complementary/alternative therapies in MS, Management of activi-ties of daily living in MS, Physical activity

(CC04) EXPERIENCES AND PERCEPTIONS OF MULTIPLE SCLEROSIS AND PREGNANCY AMONG AMERICAN HISPANICSChristopher Schroeder,1 Kerstin Hellwig,2 Jose Aparicio,1 Lilyana Amezcua1

1Neurology, University of Southern California, Los Angeles, CA; 2Neurology, Ruhr University Bochum, Bochum, Germany

Background: Little is known of the experience and perceptions of pregnancy in Hispanics with multiple sclerosis (MS). Objectives: We sought to explore women’s experiences of pregnancy with MS to help make recommendations for care. Methods: We conducted a qualitative study in a total of 37 Hispanic women with MS living in the greater Los Angeles area. Of those, 30 had successful preg-nancy experience. Marital status, education, and experiences and perceptions of MS during and after pregnancy were recorded using semistructured telephone interviews. The participants also rated their perceived severity of MS on a scale of 0 to 5, with higher numbers indicating greater severity. Results: Of the 30 women, 53% were married and 70% completed more than 2 years of college. The medi-an number of pregnancies was 2 (range, 1–10). Almost 30% (n = 7) reported that pregnancy negatively affected their MS symptoms. The mean level of perceived severity of MS was 3.2. The most commonly reported perceptions of pregnancy were “fear of passing MS to their kids” (16.7%, n = 5), “fear of relapsing or worsening of MS” (10%, n = 3), and “being scared in general” (10%, n = 3). Breastfeed-ing was common (67%) and conducted for a mean duration of 16 weeks. In 10%, the preconception of MS transmission through breast milk discouraged breastfeeding. Conclusions: Understanding His-panic women’s experiences and perceptions of pregnancy with MS can help practitioners address patients’ fears and misconceptions to better develop tools to support them.

Supported by: NoneDisclosure: Christopher Schroeder, Jose Aparicio: Nothing to disclose. Ker-stin Hellwig: Bayer-Schering Healthcare, Biogen Idec Germany, Merck Serono, Novartis Pharma, Sanofi-Aventis, Teva Pharma (grant/research support). Lilyana Amezcua: Acorda, Novartis (advisory board, grant/research support); Biogen, Questcor (advisory board); Genzyme, Teva (consulting fees).Keywords: Comprehensive care and MS, Pregnancy, Psychological issues and MS

(CC05) ASSOCIATION OF WELLNESS PRACTICES IN MULTIPLE SCLEROSIS PATIENTS USING SELF-REPORTED DISABILITY SCORES AND MS CHARACTERISTICSMary R. Rensel,1 Youran Fan2

1The Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH; 2Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, OH

Background: Multiple sclerosis (MS) patients, like everyone else, seek optimal health and wellness. MS presents special challenges to seeking wellness: the clinical characteristics, age of the patient, and

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PIADS-COMP was significantly better with the SPC (P = .004) but not the TP (P = .062) compared to the FPC. PIADS-SE was significantly better with the TP (P = .014) but not the SPC (P = .062) compared to the FPC. The PIADS-ADAPT was significantly better with the TP (P = .025) but not the SPC (P = .052) compared to the FPC. Conclu-sions: The SPC and TP generally resulted in the best improvements in walking and fatigue. Participants reported more competence with the SPC, and better self-esteem and adaptability with the TP. Both the SPC and TP may be viable options for people with MS who need an AD. The TP should be considered for people for whom self-esteem and adaptability are important considerations.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Ambulation, Equipment in MS, Psychological issues and MS

(CP02) VALIDATION OF A SHORT COGNITIVE SCREENING BATTERY TO PREDICT FITNESS-TO-DRIVE IN INDIVIDUALS WITH MULTIPLE SCLEROSISAbiodun E. Akinwuntan,1 Hannes Devos,2 Deborah Backus3

1Administration, Georgia Regents University, Augusta, GA; 2Physical Therapy, Georgia Regents University, Augusta, GA; 3Crawford Research Institute–MS Research, Shepherd Center, Atlanta, GA

Background: Determining the fitness-to-drive of individuals with multiple sclerosis (MS) usually involves the administration of 15 or more physical, visual, and cognitive tests. In the United States, the process typically lasts longer than 3 hours and costs more than $500. However, not all individuals with MS need to undergo the time-consuming and expensive process. The fitness-to-drive of some can be determined with a very good degree of accuracy based on performance on a few highly predictive tests. Objectives: In a pre-vious study, we identified five cognitive tests that together predicted the outcome of a comprehensive driving evaluation of 44 individuals with MS (age, 46 ± 11 years, 84% females) with 91% accuracy, 70% sensitivity, and 97% specificity. The five tests are the Stroop Color test; the Direction, Compass, and Road Sign Recognition tests of the Stroke Driver Screening Assessment battery; and the Speed of Processing subtest of the Useful Field of View test. In this study, we sought to validate the predictive accuracy of the five tests in a differ-ent cohort of individuals with MS. Methods: Sixty-three participants (age, 49 ± 9 years, 89% females) were administered the five cogni-tive tests. Participants were also administered a standardized practi-cal on-road driving test. Performance on the road test was judged by completing a 16-item checklist of very important driving skills. A raw score of 45 or more out of 50 maximum points was classified as “pass” and below 45 as “fail.” Performance on the five cognitive tests was used to predict the pass/fail outcome of the on-road test. Results: All five variables each had significant association with the on-road test raw score. The five tests together explained 44% of the variance of the pass/fail classification. Participants’ “pass” or “fail” performance on the road test was predicted with 83% accuracy, 67% sensitivity, and 85% specificity. Conclusions: The short battery of five tests, which together can be completed in less than 1 hour and should cost less than $250, appears to be a valid predictor of fitness-to-drive of individuals with MS (83% accuracy) and more accurate at predicting individuals who will pass an on-road evaluation (85% specificity) than those who will fail (67% sensitivity).

Supported by: National Multiple Sclerosis SocietyDisclosure: Nothing to discloseKeywords: Cognition and driving, Comprehensive care and MS, Management of activities of daily living in MS

(CP03) MODIFIABLE PREDICTORS OF SELF-RATED COGNITIVE ABILITIES IN PEOPLE WITH MULTIPLE SCLEROSISAshley Henneghan, Janet Morrison, Alexa Stuifbergen

School of Nursing, The University of Texas at Austin, Austin, TX

determined intervention usefulness. Results: The participant demon-strated improved pre-post intervention scores for measures of ESES, MSIS-29, MFIS, and PHQ-9, demonstrating higher self-rated exercise self-efficacy and health, and reduced disability and fatigue. Gait speed was unchanged. Sleep quality and morning fatigue improved from week 1 to 16, while evening fatigue was unchanged. Activity monitoring data will also be presented. The participant reported the educational presentations and “mentor” sessions to be very valuable, with the daily journal perceived as the least valuable component of the intervention. Conclusions: Preliminary results from this case study suggest that an 8-week self-efficacy intervention can increase exercise self-efficacy and QOL and reduce perceived fatigue in a severely disabled individual with secondary progressive MS. Future research should examine self-efficacy interventions in a larger sample size of people with progressive MS.

Supported by: National Multiple Sclerosis Society, Greater Carolinas ChapterDisclosure: Nothing to discloseKeywords: Management of activities of daily living in MS, Psychological issues and MS, Self-efficacy

COGNITION AND PSYCHOSOCIAL

(CP01) TREKKING POLES TO AID MULTIPLE SCLEROSIS (TRAMS): A COMPARISON OF PSYCHOSOCIAL IMPACT AND FUNCTION WITH WALKING ASSISTIVE DEVICES IN PEOPLE WITH MULTIPLE SCLEROSISDonald A. Barone,1 Evan T. Cohen,2 Sara Soliman,1 Christine Beswick,1 Eric Goldwasser,1 Adil Manzoor,1 Alison Caruana,1 Nishant Parikh1

1Medicine/Neurology, Rowan University–SOM, Stratford, NJ; 2Department of Rehabilitation and Movement Sciences, Rutgers, The State University of New Jersey, Stratford, NJ

Background: Walking difficulty is the most common physical functional complaint reported by people with multiple sclerosis (MS). Initial discussions about the use of assistive devices (ADs) to mitigate this difficulty are often met with resistance and denial of the need for an AD because of the perceived psychosocial impact of its use. Objectives: To compare the psychosocial impact of, and walk-ing function with, three ADs in people with MS: a single-point cane (SPC), a narrow-based four-point cane (FPC), and a trekking pole (TP). Methods: Fourteen people with a confirmed diagnosis of MS (12 women and 2 men; ages 33–64 years, mean = 52.3 years) and an Expanded Disability Status Scale (EDSS) score of 2.5 to 6 (mean = 4.2) completed the study. Baseline data (ie, without an AD) includ-ed the 12-item Multiple Sclerosis Walking Scale (MSWS-12), Activity-specific Balance Confidence Scale (ABC), 5-item Modified Fatigue Impact Scale (MFIS-5), and 6-minute Walk Test (6MWT) distance. The difference in a visual analogue scale of fatigue (ΔVAS-F) given immediately before and after the 6MWT measured fatigue induced by the 6MWT. Participants were provided with the SPC, FPC, or TP in a randomized, cross-over order. At baseline and each follow-up point, participants were trained in the use of the respective AD, and were provided it for use. Participants returned within 1–2 weeks and repeated the testing battery using the AD (MSWS-12, ABC, MFIS-5, 6MWT) and also completed the Psychosocial Impact of Assistive Devices Scale (PIADS) from which three subscales were derived: Competence (PIADS-COMP), Self-esteem (PIADS-SE), and Adapt-ability (PIADS-ADAPT). Within-subject differences between conditions were examined with repeated-measures ANOVAs with planned pairwise comparisons. Results: Participants walked farther in the 6MWT with the SPC (P = .003) and the TP (P = .006) compared to the FPC. No difference in ΔVAS-F was induced by the 6MWT between AD conditions (P = .162). There were improvements in MSWS-12 between the SPC (P = .005) and TP (P = .003) compared to baseline. The MFIS-5 was better (ie, lower) with the TP compared to baseline. There were no differences in ABC (P = .103) between conditions. Differences were found in all three PIADS subscales.

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tive impairment. The PDQ is a 20-item Likert scale, which addresses several cognitive measures that are affected by MS, including ret-rospective memory, prospective memory, planning/organization, and attention. Participants in the treatment group will complete 5 weeks (3 sessions/week) of an online computer-based cognitive retraining program, Brain HQ, accessed from their home. BrainHQ is supported by over 70 publications in schizophrenia, chemobrain, HIV-associated neurocognitive disorder, traumatic brain injury, stroke, and age-related cognitive decline. Retraining sessions will focus on memory, attention, and information processing. Both the control and treatment groups will complete the posttest SFCT and PDQ 5-8 weeks after pretesting. Results: This study is ongoing. The investiga-tors hypothesize that an improvement in quality of life and cognitive function will be demonstrated by posttest PDQ and SFCT scores. The short duration of the study may be a limitation for demonstrating an improvement in cognitive function. Conclusions: Results of this pilot study should support the need for continued clinical research into cognitive retraining for individuals with MS. Cognitive retraining may not only improve cognition, but have positive effects on quality of life.

Supported by: Biogen Idec Investigator Initiated GrantDisclosure: Biogen Idec (consulting fees, grant/research support)Keywords: Cognitive rehabilitation, Complementary/alternative therapies in MS

(CP05) A CALL TO EXPLORE THE ETIOLOGY OF DEPRESSION UNDERLYING THE REPORT OF COGNITIVE CONCERNS IN PATIENTS WITH MULTIPLE SCLEROSISRebecca M. Floyd, Kimberly Lewis, Eliot Lopez, Thomas Toomey, Kena Arnold, Lara Stepleman

Georgia Regents University, Augusta, GA

Background: Depression is known to strongly affect cognitive functioning, particularly initiation, spontaneous recall, and process-ing speed. Core symptoms of depression that overlap with hallmark symptoms of multiple sclerosis (MS) include low mood, anhedonia, and fatigue, any of which could conceivably reduce performance on cognitive tasks. However, understanding the etiology of cognitive symptoms may be important to developing effective and appropriate treatment interventions. Objectives: This study presents an initial attempt to examine whether anhedonia or low mood, two symptoms that are routinely screened for in identifying patients who might be experiencing depression, is more strongly associated with report of cognitive concerns. Methods: Data were collected on a sample of MS patients who were screened as part of routine care at an MS clinic in the southeastern United States (N = 259, 79.5% female, 55% white, mean age 46.67 years). Cognitive concerns were sub-jectively reported. Anhedonia and mood were assessed using the 2-item Patient Health Questionnaire for depression (PHQ-2; Kroenke, Spitzer & Williams, 2003). Results: Results from logistic regression show that anhedonia was not significantly associated with report of cognitive concerns (P = .718) and that patients who reported depressed mood were 3.5 times more likely to report concerns with cognitive functioning (P = .006) than those denying mood complaint. Conclusions: In light of these results, professionals may want to give greater consideration to interventions directly elevating mood, in the treatment of depression when cognition is also of concern, than to behavioral activation and stimulation. Although anhedonia was not significantly related to cognitive concerns in this limited exploration, teasing apart anhedonia from fatigue may be advisable to uncover masked effects of anhedonia versus fatigue, as many patients com-mented during screening that their experience of anhedonia was driven by MS-related fatigue. Providing an additional assessment of MS fatigue when anhedonia is endorsed may assist with further exploring etiology of depression and its relationship to cognitive functioning.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Comprehensive care and MS, Psychological issues and MS

Background: Research suggests that common multiple sclerosis (MS)–related symptoms such as stress, depression, fatigue, and pain may have negative effects on individuals’ perceptions of their cogni-tive abilities. While these symptoms are prevalent in people with MS, they may also be viewed as modifiable within the clinical setting. However, little is known about how these symptoms may predict perceived cognitive abilities in people with long-standing (greater than 15 years) MS. Objectives: To explore whether modifiable disease-related symptoms (stress, fatigue, pain) are significant predic-tors of self-rated cognitive abilities while controlling for age, disease duration, and years of education in people with MS who have been diagnosed for more than 15 years. Methods: A sample of 300 people with MS (88% female, mean age 64.3 ± 9.0; mean disease duration 27.3 ± 6.6 years) in an ongoing longitudinal health promo-tion study completed the Perceived Stress Scale, the CES-Depression Scale, and three NIH PROMIS scales: Pain Intensity, Fatigue, and Cognitive Abilities. Reliability coefficients for all summated scales exceeded 0.85. Descriptive statistics, Pearson correlations, and hierarchical regression were used to analyze the data. Results: Perceived stress, depressive symptoms, and fatigue scores were highly correlated with scores of the measure of perceived cognitive abilities (r = −0.58, −0.58, and −0.61; P < .001, respectively) while pain intensity was moderately correlated (r = −0.37, P < .001). Thus, as negative disease-related symptoms increase, perceived cognitive abilities decrease. Age, disease duration, and years of education explained 4.3% of the variability in perceived cognitive abilities. Perceived stress, depressive symptoms, fatigue, and pain together explained significant additional variability in cognitive abilities (ΔR = 0.436, F4,287 = 60.13, P < .001). Conclusions: Findings support the expected theoretical relationships between modifiable symptoms and perceived cognitive abilities and are consistent with research findings in other populations. Importantly, the symptoms discussed here (perceived stress, depressive symptoms, and fatigue) are largely modifiable with behavioral interventions and could be targets for future interventions to improve perceived cognitive abilities in people with long-standing MS.

Supported by: James R. Dougherty Jr. Centennial Professorship in Nursing, The University of Texas at Austin, School of Nursing; National Institute of Nursing Research, National Institutes of Health (grant F31 NR014601)Disclosure: Nothing to discloseKeywords: Cognition and MS, Psychological issues and MS

(CP04) COGNITIVE IMPAIRMENT IN MULTIPLE SCLEROSIS: A PILOT STUDY OF THE EFFECTS OF COGNITIVE RETRAINING ON QUALITY OF LIFE AND IMPROVEMENT IN COGNITIVE FUNCTIONMeagan Adamson

Multiple Sclerosis Center, Neurology Center of Fairfax, Fairfax, VA; Doctor of Nursing Practice Program, Chamberlain College of Nursing, Downers Grove, IL

Background: Review of current research reveals mixed findings on the efficacy of cognitive rehabilitation in multiple sclerosis (MS). Studies suggest that cognitive retraining can improve quality of life and cognitive function in MS, but the applicability of data is limited. This pilot study will explore the use of cognitive retraining in MS. Objectives: To evaluate the improvement in quality of life and cognition after cognitive retraining. Methods: Patients with MS will be screened for mild cognitive impairment using a validated short form cognitive test (SFCT). The SFCT includes the following assessments: Verbal Category Fluency, Boston Naming, Mini-Mental State Examination, Hopkins Verbal Learning, Digit Span (Forward, Backward, and Sequential), Hopkins Verbal Learning Recall, Hopkins Verbal Learning Recognition, Trails A & B, and Beck Depression Inventory. Up to 40 eligible participants will be randomly assigned to control and treatment groups. All participants will complete the Perceived Deficits Questionnaire (PDQ). The PDQ is a component of the Multiple Sclerosis Quality of Life Inventory (MSQLI). The PDQ was designed specifically for MS to provide a self-report of cogni-

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Neurological Institute, McGill University, Montreal, QC, Canada; 5Charles University in Prague, Prague, Czech Republic; 6Moscow Multiple Sclerosis Center, Moscow, Russia; 7University of Münster, Münster, Germany; 8Department of Neurology, University of Utah, and Neurovirology Research Laboratory VASLCHCS, Imaging and Neuroscience Center, Salt Lake City, UT; 9AbbVie Biotherapeutics Inc, Redwood City, CA; 10Biogen Idec, Inc, Cambridge, MA

Background: Maintaining the functional domains associated with the ability to perform daily activities, such as ambulation and cogni-tion, is a priority for patients with multiple sclerosis (MS). Hence, patient-centered functional outcomes have been included in recent and ongoing efficacy trials of MS therapies. One such trial, the ran-domized, double-blind DECIDE study, has already reported that DAC HYP reduced clinical and radiographic disease activity in patients with relapsing-remitting MS (RRMS) compared with intramuscular interferon beta-1a (IFNβ-1a). Objectives: To evaluate the effects of DAC HYP compared with IFNβ-1a on different patient-centered functional domains, including ambulation, hand/arm dexterity, and cognition, using the Multiple Sclerosis Functional Composite (MSFC) and Symbol Digit Modalities Test (SDMT) in the DECIDE trial. Meth-ods: Patients (aged 18–55 years) with confirmed RRMS and an Expanded Disability Status Scale (EDSS) score of 0.0 to 5.0 were randomized to DAC HYP 150 mg subcutaneously every 4 weeks or IFNβ-1a 30 µg once weekly. Changes in MSFC and SDMT over 96 weeks were tertiary endpoints, and treatment differences were evaluated using analysis of covariance on ranks (MSFC) or mixed-effects models (SDMT), adjusted for key baseline parameters, includ-ing baseline score. Results: Overall, 919 patients received DAC HYP (mean baseline EDSS 2.48) and 922 IFNβ-1a (EDSS 2.54). Over 96 weeks, the median (25th, 75th percentile) improvement from baseline in the MSFC z score was 0.091 (−0.096, 0.287) for DAC HYP versus 0.055 (−0.136, 0.240) for IFNβ-1a (P = .0007). Significant differences between the DAC HYP and IFNβ-1a groups were also observed in the MSFC components. Median (25th, 75th percentile) z score change from baseline to week 96 was as fol-lows: Timed 25-Foot Walk: 0.000 (−0.099, 0.083) versus −0.017 (−0.124, 0.075; P = .0060); Nine-Hole Peg Test: 0.063 (−0.195, 0.356) versus 0.017 (−0.273, 0.291; P = .0016); and Paced Auditory Serial Addition Test-3: 0.177 (−0.088, 0.530) versus 0.177 (−0.088, 0.442; P = .0411). For the SDMT, the mean (±SD) change from baseline over 96 weeks of DAC HYP therapy was 4.08 (±12.40), compared with 2.89 (±12.71; P = .0274) for IFNβ-1a. Conclusions: Over 2 years of treatment, DAC HYP showed greater improvement compared with IFNβ-1a on the MSFC and SDMT outcomes.

Supported by: Biogen Idec, AbbVie Biotherapeutics IncDisclosure: Michael Kaufman: Biogen Idec (grant/research support); Biogen Idec, Bayer, EMD Serono, Novartis, Teva (consulting fees). Ludwig Kappos: Nothing to disclose. Krzysztof W. Selmaj: Biogen Idec, Genzyme, Novartis, Ono, Roche, Synthon, Teva (consulting fees). Douglas L. Arnold: Bayer HealthCare, Biogen Idec Inc, EMD Serono, Genentech, Genzyme, GlaxoSmithKline, Novartis, Roche, Merck Serono, Teva (consulting fees); NeuroRx Research (ownership interest, sal-ary). Eva Havrdova: Biogen Idec (grant/research support); Bayer Schering Health-care, Biogen Idec, Genzyme, Merck Serono, Novartis, Teva (consulting fees). Alex-ey Boyko: Bayer Schering, Merck Serono, Teva, Novartis, Biogen Idec, Nycomed, Genzyme, Sanofi-Aventis (consulting fees). Heinz Wiendl: Bayer HealthCare, Biogen Idec, Fresenius Medical Care, GlaxoSmithKline, GW Pharmaceuticals, Merck Serono, Novartis, Sanofi-Genzyme BioVentures, Teva Pharmaceutical Industries (consulting fees); Bayer HealthCare, Biogen Idec, German Ministry for Education and Research, Deutsche Forschungsgesellschaft, Else Kröner Fresenius Foundation, Fresenius Foundation, Hertie Foundation, Merck Serono, Novartis, NRW Ministry of Education and Research, Interdisciplinary Center for Clinical Studies in Münster, Germany, RE Children’s Foundation, Sanofi-Aventis/Gen-zyme, Teva Pharmaceutical Industries (grant/research support). John Rose: Biogen Idec, AbbieVie Biotherapeutics, Teva, Cumming Foundation, National Multiple Sclerosis Society, Veterans Administration, National Institutes of Health (grant/research support). Steven J. Greenberg: AbbVie (salary); AbbVie Biotherapeutics (ownership interest). Marianne T. Sweetser, Mark Beatty: Biogen Idec (ownership interest, salary). Wei Ma, Ping Wang: Biogen Idec (salary).Keywords: Disease-modifying treatments in MS, Patient-centered outcomes and functional disability

(CP06) ASSESSMENT OF INFORMATION PROCESSING SPEED IN MULTIPLE SCLEROSIS: PAST AND FUTURESilvana L. Costa,1,2 Helen Genova,1,3 John DeLuca,1 Nancy D. Chiaravalloti1,3

1Neuropsychology and Neuroscience Research, Kessler Foundation, West Orange, NJ; 2School of Medicine, Rutgers University, West Orange, NJ; 3School of Medicine, Rutgers University, Newark, NJ

Background: Information processing speed (IPS) deficits are preva-lent among individuals with multiple sclerosis (MS). Objectives: The present review aims to summarize how IPS has been assessed during the last decade. Methods: A PubMed search with key words “processing speed” AND “MS” for articles published from 1/1/04 to 12/31/13 and two inclusion screens resulted in 157 articles. Results: IPS has been mostly assessed with heterogeneous samples (combined disease course) (53.5%). Fewer studies focused on one disease course (33.8%), and as few as 9.6% examined differences between disease courses. Studies often controlled for presence of other neurologic disorders (61.54%), age (58.60%), education (51.59%), use of alcohol (47.77%), or use of steroids (39.49%). Although relapses are known to affect functioning, only 50.32% of studies report controlling for time since last exacerbation. Although studies assess cognitive functions, only 19.11% controlled for history of developmental disorders. Visual problems are a common symptom in MS, yet just 29.30% of studies report visual function evaluation. This is important, since the majority of tests used to assess IPS are visual. Longitudinal studies are scarce (10%), and none examined the efficacy of rehabilitation interventions. Tests were grouped into seven categories to understand frequency of usage. The most popular tests to assess IPS in MS were symbol/digit substitution tests (132 times), followed by tests designed to measure working memory (111). Reac-tion time tests were used 44 times to assess IPS, with tests designed to measure executive functioning being used 42 times. Less often utilized were tests designed to measure attention (13), verbal fluency (6), or other domains (12). While the use of symbol/digit modalities tests increased 23.71% between the first 5 years and the second 5 years of the decade, tests designed to measure WM/executive func-tions decreased 10.79% in the same time period. This observation might be related to the recognition of the cognitive complexity inher-ent in the Paced Auditory Serial Addition Test and the emotional bur-den. Additionally, accumulating evidence over the last decade has built support for the sensitivity of the SDMT to IPS deficits in people with MS. Conclusions: Our understanding of IPS deficits in MS has advanced notably during the last decade. Our future goal should be to increase our understanding of the variability of IPS between the different disease courses, with a focus on the impact of IPS deficits on everyday functional abilities. When selecting participants, atten-tion should be paid to premorbid pathologies that affect cognitive performance (eg, developmental disorders), disease progression (eg, last exacerbation), and sensorial function (visual and motor). More longitudinal and rehabilitation studies will be essential to further our understanding of IPS deficits in MS and their impact on daily func-tioning and quality of life.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Information processing speed in MS

DISEASE MANAGEMENT, MECHANISMS, AND TREATMENT

(DX01) THE EFFECT OF DACLIZUMAB HIGH-YIELD PROCESS (DAC HYP) ON PATIENT-CENTERED FUNCTIONAL OUTCOMES: RESULTS FROM THE DECIDE STUDYMichael Kaufman,1 Ludwig Kappos,2 Krzysztof W. Selmaj,3 Douglas L. Arnold,4 Eva Havrdova,5 Alexey Boyko,6 Heinz Wiendl,7 John Rose,8 Steven J. Greenberg,9 Marianne T. Sweetser,10 Wei Ma,10 Ping Wang,10 Mark Beatty10

1Cole Neurological Institute, University of Tennessee–Knoxville, Knoxville, TN; 2University Hospital Basel, Basel, Switzerland; 3Medical University of Lodz, Lodz, Poland; 4Montreal

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committees, fees for non-CME services from commercial interests or their agents); Actelion, Biogen Idec, MedDay, Novartis, Questcor, Teva, XenoPort (consulting fees); Novartis (grant/research support).Keywords: Cannabinoids, Management of activities of daily living in MS

(DX03) ALEMTUZUMAB IMPROVES DISABILITY AFTER SWITCH FROM OTHER DISEASE-MODIFYING THERAPIES IN A HIGH-DISABILITY TREATMENT-REFRACTORY RELAPSING MULTIPLE SCLEROSIS COHORTSamuel F. Hunter,1,2 Isabelle St. Clare-Hunter,1,2 Justin M. Amburgey,1 Gregory J. Dick,1 Kristen B. Sherman,1 Madelyn B. Rarick,1 Daniel Kantor2

1Advanced Neurosciences Institute, Franklin, TN; 2NeuroNexus Center–Novel Pharmaceutics Institute, Franklin, TN

Background: Treatment-refractory multiple sclerosis (TRMS) (eg, recurrent relapses and worsening disability on therapy) remains challenging. Nihilism and bias against therapy for “secondary pro-gressive” MS, worsening gait, or poor Expanded Disability Status Scale (EDSS) scores may become obsolete with evidence of treatment benefit. Alemtuzumab (ALE), an FDA-approved, humanized anti-CD52, cytotoxic monoclonal IgG, produces selective and transient lymphopenia and subsequent immune reconstitution. ALE achieves superior EDSS outcomes over high-dose interferon beta-1a in relaps-ing MS. An early phase 1 ALE study suggested stability in patients with progressive features, and our prior retrospective reports support long-term EDSS improvement in TRMS. Given risk-benefit ratio, ALE may also be appropriate for higher-disability, active patients differ-ing from the strictly relapsing lower-disability, short-disease-duration profile of phase 2/3 clinical trials. Objectives: Report outcome measures EDSS and MS Severity Scale (MSSS) changes following ALE by prior therapy and follow-up duration. Methods: Phase 1 prospective analysis of EDSS and MSSS change following ALE. Inclusion criteria: prior immunotherapy failure and relapse within 2 years, regardless of apparent progressive features. 60 ALE-treated TRMS subjects were followed prospectively. Groups were stratified by 1) median lunar months follow-up (MFU) duration: long-term (LT) 82 MFU (27–104, n = 30) or short-term (ST) 10 MFU (6–25, n = 30), and 2) therapies immediately before and within the prior 2-year epoch before ALE: interferon beta or glatiramer acetate (IFNGA), fin-golimod (FTY), and natalizumab (NAT). Results: The LT cohort had median baseline EDSS 5.5 (2.0–7.5) and MSSS 6.7 (1.7–9.6). The ST cohort had median baseline EDSS 5.0 (2.5–7.0) and MSSS 6.3 (1.3–9.9). Following ALE, mean EDSS change LT was −1.0 (−4.0 to +2.0) and ST −0.4 (−4.5 to +1.5). Mean MSSS change LT was −2.34 (−6.84 to +0.89) and ST −0.54 (−2.82 to +1.16). For com-bined cohorts, EDSS changes from therapy immediately prior to ALE were: IFNGA −0.9 (n = 26, 82 MFU), FTY −0.4 (n = 14, 12 MFU), NAT −0.5 (n = 11, 49 MFU). EDSS changes for therapies within 2 years prior to ALE were: IFNGA −0.8 (n = 34, 61 MFU), FTY −0.4 (n = 14, 12 MFU), NAT −0.2 (n = 29, 13 MFU). A subset cohort of previously NAT-treated patients received FTY immediately prior to ALE with change of EDSS −0.4 (n = 10, 12 MFU). Conclusions: ALE provides immunotherapeutic rescue for most TRMS patients, with group-wise EDSS and MSSS improvement, notwithstanding other recent, effective, and even aggressive prior therapies. Improvement in ST likely becomes more prominent in our cohort with LT follow-up. This improvement favors treatment of high-disability TRMS. Our cohort benchmarks expected outcomes following ALE for TRMS after standard immunotherapy. Evidence supports ongoing LT sustained disability improvement after more than 5 to 8 years, regardless of prior immunotherapy.

Supported by: Genzyme-SanofiDisclosure: Samuel F. Hunter: Bayer, Biogen Idec, Genzyme-Sanofi, Novartis (consulting fees, fees for non-CME services from commercial interests or their agents, grant/research support); Osmotica (consulting fees, grant/research support); Teva (fees for non-CME services from commercial interests or their agents, grant/research support). Isabelle St. Clare-Hunter, Justin M. Amburgey, Gregory J. Dick, Kristen B. Sherman: Nothing to disclose. Madelyn B. Rarick: Genzyme-Sanofi (consulting fees). Daniel Kantor: Biogen Idec, Novartis (consulting fees,

(DX02) CURRENT MARIJUANA USAGE BY MULTIPLE SCLEROSIS STATUS AND DISABILITY IN THE NARCOMS REGISTRYStacey S. Cofield,1 Amber R. Salter,1 Tuula Tyry,2 Sandre McNeal,1 Gary Cutter,1 Ruth Ann Marrie,3 Robert J. Fox4

1Biostatistics, University of Alabama at Birmingham, Birmingham, AL; 2Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ; 3University of Manitoba, Winnipeg, MB, Canada; 4Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH

Background: Recent research suggests that cannabinoids can help alleviate some symptoms of multiple sclerosis (MS). Individual state and US laws are changing regarding marijuana and medical mari-juana. Objectives: To assess current marijuana usage by current MS type and disability level as measured by the Patient-Determined Disease Steps (PDDS). Methods: In August 2014, all active par-ticipants (12,260) in the North American Research Committee on Multiple Sclerosis (NARCOMS) were invited to complete an online, anonymous questionnaire with sociodemographic and clinical char-acteristics including current PDDS and type of MS: relapsing-remitting MS, active with a relapse in prior 2 years (RRMS-A), relapsing but stable (RRMS-S), progressive but used to have relapses (SPMS), and progressive from onset with no prior relapses (PPMS). Marijuana referred to smoking and ingesting marijuana or any controlled sub-stance derived from marijuana or synthetic marijuana. Results are summarized as mean (SD), median (IQR), or percent, as applicable. Results: Of 5665 respondents, 78.3% were women, the current mean (SD) age was 55.5 (10.2) years, and the median (IQR) age at diagnosis was 37 (29–45) years. MS was relapsing from onset in 90.2% of respondents: 26.5% RRMS-A, 42.8% RRMS-S, 20.9% SPMS, and 9.8% PPMS. Participants with PPMS onset were older at diagnosis (44 [35–51] vs. SPMS 35 [28–42], RRMS-S 37 [29–44], RRMS-A 36 [29–43]; all P < .0001) and time of survey (62 [57–67] vs. SPMS 59 [54–64], RRMS-S 55 [48–62], RRMS-A 54 [45–60]; all P < .0001) and more likely to be male (35.8% vs. SPMS 28.4, P = .0021; RRMS-S 17.5, RRMS-A 18.2, both P < .0001). Those with PPMS had worse current disability (PDDS 5 [4–7] compared to RRMS-A 3 [2–4] and RRMS-S 2 [0–4], both P < .0001). 906 (16.0%) participants reported current marijuana usage. When adjust-ed for current age and gender, those with RRMS-S were least likely to currently be using marijuana compared to all other types: PPMS vs. RRMS-S (OR 1.4, P = .0232), SPMS (OR 1.7, P < .0001), RRMS-A (1.5, P < .0001); and those with PDDS 0 (normal) were less likely to currently use marijuana compared to all levels except PDDS 8 (bed-ridden, all P < .005), while those with PDDS 1 (mild disability) were less likely to currently use compared to PDDS 2 (moderate) through 5 (late cane) (all P < .05). There was no difference in the median days per month for those reporting use by type of MS: 20 (IQR 5–20; P = .22). Conclusions: Those with higher current disability and those reporting active relapsing or progressive disease were more likely to report current marijuana usage.

Supported by: CMSC, Foundation of the CSMCDisclosure: Stacey S. Cofield: MedImmune, American Shoulder Elbow Society (consulting fees). Amber R. Salter: GlaxoSmithKline (DSMB service). Tuula Tyry, Sandre McNeal: Nothing to disclose. Gary Cutter: Antisense Therapeutics Limited, Sanofi-Aventis, Bayhill Pharmaceuticals, Bayer Pharmaceuticals, BioMS Pharmaceuticals, Daichi-Sankyo, GlaxoSmithKline Pharmaceuticals, Genmab Biopharmaceuticals, Medivation, Peptimmune, PTC Therapeutics, Teva, Vivus, National Heart, Lung, and Blood Institute, National Institute of Neurological Disorders and Stroke, National Multiple Sclerosis Society (DSMB service); EMD Serono, EDJ Associates, Aegis Creative Marketing, Eli Lilly, UT Southwestern University, Klein Buendel, University of Illinois Health Policy Center, Somnus Therapeutics, Klein-Buendel Incorporated, Enzo Pharmaceuticals, Somnus Pharmaceuticals, Teva, Biogen Idec, Advanced Health Media, Alexion, Accentia, Barofold, CibaVision, Biogen Idec, Novartis, Consortium of Multiple Sclerosis Centers (consulting fees). Ruth Ann Marrie: CIHR, PHAC, MHRC, HSC Foun-dation, MS Society of Canada, MS Scientific Foundation, CMSC Foundation, Rx & D Health Research Foundation, Bayer Inc, Sanofi-Aventis, EMD Serono (grant/research support). Robert J. Fox: Actelion, Biogen Idec, Novartis (advisory

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1The University of British Columbia, Vancouver, BC, Canada; 2Heinrich-Heine University, Düsseldorf, Germany; 3First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; 4Medical University of Lodz, Lodz, Poland; 5University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom; 6Genzyme, a Sanofi company, Cambridge, MA; 7PROMETRIKA, LLC, Cambridge, MA; 8NeuroRx Research, Montreal, QC, Canada; 9Montreal Neurological Institute, McGill University, Montreal, QC, Canada

Background: In the CARE-MS II trial (NCT00548405), alemtu-zumab had superior effects versus subcutaneous interferon beta-1a, including improved magnetic resonance imaging (MRI) outcomes over 2 years, in relapsing-remitting multiple sclerosis (RRMS) patients with an inadequate efficacy response to prior therapy. Objectives: Examine the effect of alemtuzumab on 4-year MRI outcomes in CARE-MS II patients who entered an ongoing extension. Methods: In the CARE-MS II core study, patients with ≥1 relapse after ≥6 months on prior therapy were randomized to alemtuzumab and received 12 mg/day intravenously on 5 consecutive days and on 3 consecutive days 12 months later. In the extension study (NCT00930553), these patients could receive as-needed retreatment ≥1 year after a previous course. MRI scans were acquired at baseline and yearly thereafter. MRI outcomes included gadolinium (Gd)-enhancing, new/enlarging T2 hyperintense and new T1 hypointense lesion activity, freedom from MRI activity (absence of Gd-enhancing and new/enlarging T2 lesions), and brain volume loss measured by brain parenchymal frac-tion (BPF) change. Results: 393 (92.9%) CARE-MS II alemtuzumab-treated patients entered the extension. Through 4 years, 67.7% of patients received only the initial 2 courses of treatment, 24.2% received 1 additional course, and 7.4% received 2 additional courses. In year 3 and year 4, the proportions of patients free of Gd-enhancing (86.5% and 89.1%), new/enlarging T2 (69.0% and 70.3%) or new T1 lesions (87.5% and 86.3%) remained stable. Most patients were MRI activity-free at year 3 (68.4%) and year 4 (69.9%). Median rate of BPF loss progressively slowed over 3 years and remained low in year 4 (year 1: –0.48%, year 2: –0.22%, year 3: –0.10%, year 4: –0.19%). Conclusions: The majority of alem-tuzumab patients remained free of new lesions and MRI activity in years 3 and 4 despite most patients not receiving more than the ini-tial 2 treatment courses, and slowing of brain volume loss was main-tained over the 4-year period. These findings support the durable efficacy of alemtuzumab in this RRMS population.

Supported by: Genzyme, a Sanofi company; Bayer HealthCare PharmaceuticalsDisclosure: Anthony Traboulsee: Biogen, Chugai, Genzyme, MedImmune, Novartis, Roche, Serono, Teva Innovation (consulting fees); Genzyme, Roche (grant/research support). Hans-Peter Hartung: Bayer HealthCare, Biogen Idec, CSL Behring, Genzyme, Hoffmann-LaRoche, Novartis, Octapharma, Sanofi, Teva (consulting fees). Eva Havrdova: Biogen Idec, Genzyme, Merck, Novartis, Receptos (consulting fees); Biogen Idec (grant/research support). Krzysztof W. Selmaj: Biogen Idec, Roche, Merck, Synthon, Genentech, Genzyme (consulting fees). D. Alastair S. Compston: Genzyme, Lundbeck Foundation (consulting fees). David H. Margolin: Genzyme, a Sanofi company (salary). Linda Kasten: Genzyme, a Sanofi company (consulting fees). Douglas L. Arnold: Acorda Thera-peutics, Biogen Idec, Genzyme, MedImmune, Mitsubishi, NeuroRx Research, Novartis, Roche, Teva (consulting fees).Keywords: Alemtuzumab, Disease-modifying treatments in MS, Imaging and MS

(DX06) INCREASED APOLIPOPROTEIN A-I LEVELS IMPROVE CLINICAL AND BIOLOGICAL MARKERS IN EAELidia Gardner, Michael Levin

Neurology, University of Tennessee HSC, Memphis, TN

Background: Apolipoprotein A-I (ApoA-I) is the lipid of highest con-centration in the cholesterol molecule and has been shown to have anti-inflammatory properties. It is also overexpressed in the brain and spinal cord. Recent studies revealed that progressive multiple sclerosis (MS) patients have lower serum levels of ApoA-I compared to healthy individuals or relapsing-remitting MS patients (Meyers et al., J Neuroimmunology. 2014;277:176–185). Objectives: We hypothesized that ApoA-I levels might cause clinical and biological changes in experimental autoimmune encephalomyelitis (EAE), a

fees for non-CME services from commercial interests or their agents, grant/research support).Keywords: CNS repair, Disease-modifying treatments in MS, Natural history of MS

(DX04) DISEASE ACTIVITY DURING THE FIRST YEAR PREDICTS CLINICAL LONG-TERM OUTCOMES IN PATIENTS WITH MULTIPLE SCLEROSIS: FINGOLIMOD TREATMENT BENEFITPavle Repovic,1 Erik Burton,2 Xiangyi Meng,3 Daniela Piani Meier,3 Frederik Barkhof4

1Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA; 2US Health Economics & Outcomes Research, Novartis Pharmaceuticals Corporation, East Hanover, NJ; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ; 4Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands

Background: Early magnetic resonance imaging (MRI) activity and/or relapses have been explored for their ability to predict long-term clinical outcomes in patients with relapsing forms of multiple sclerosis (MS). Objectives: To assess whether MRI activity and/or relapses during the first 12 months of TRANSFORMS predicted later clinical outcomes, and to assess clinical outcomes in patients who switched from intramuscular (IM) interferon beta-1a (IFNβ-1a) to oral fingolimod after 12 months. Methods: This is a post hoc analysis of the 36-month follow-up of TRANSFORMS, a double-blind, random-ized, phase 3 study of fingolimod (0.5 mg or 1.25 mg daily) versus IFNβ-1a IM (30 µg weekly). On entering the extension, patients randomized to IFNβ-1a IM were re-randomized to either fingolimod 0.5 mg or 1.25 mg (switch group). Unadjusted logistic regression was used to assess whether MRI activity (defined as one or more T1 Gd-enhancing lesions or two or more T2 lesions) and/or one or more relapses during months 0 to 12 of treatment predicted relapses or 6-month confirmed disability progression (CDP) as measured by Expanded Disability Status Scale (EDSS) at months 12 to 24 and 12 to 48. Results: In total, 1292 patients were randomized in the core phase, with 1030 (79.7%) entering the extension phase. MRI activity in the first year was predictive of relapses or 6-month CDP (months 12–24: odds ratio [OR] 1.359, 95% confidence interval [CI] 0.958–1.926, P = .0851; months 12–48: OR 1.701, 95% CI 1.246–2.322, P = .0008). Relapses in the first year were also predictive of relapses or 6-month CDP (months 12–24: OR 2.096, 95% CI 1.654–2.655, P < .0001; months 12–48: OR 2.008, 95% CI 1.541–2.616, P < .0001). Additionally, combined MRI activity and relapses in the first year were predictive of relapses or 6-month CDP (months 12–24: OR 2.695, 95% CI 1.643–4.420, P < .0001; months 12–48: OR 3.030, 95% CI 1.761–5.212, P < .0001). The proportions of patients with MRI activity and/or relapses during months 0 to 12 was 4.9% for fingolimod 0.5 mg and 12.9% for IFN; at months 12 to 24, the proportion for continuous fingolimod remained low (3.2%) while the proportion in patients who switched from IFN to fingolimod decreased to 3.9%. Conclusions: MRI activity and/or relapses during the first year of TRANSFORMS were predictors of later clinical outcomes. Switching from IFNβ-1a to fingo-limod after 12 months reduced the proportion of patients experienc-ing later MRI activity and relapses.

Supported by: Novartis Pharmaceuticals CorporationDisclosure: Pavle Repovic: Acorda Therapeutics, Biogen Idec, EMD Serono, Genzyme, Novartis Pharmaceuticals Corporation, Pfizer, Teva Pharmaceuticals (consulting fees). Erik Burton, Xiangyi Meng: Novartis Pharmaceuticals Corpo-ration (salary). Daniela Piani Meier: Novartis Pharma AG (salary). Frederik Barkhof: Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis, Genzyme, Roche, Teva (consulting fees).Keywords: Fingolimod, MRI, Predictors, Relapses

(DX05) DURABLE EFFECT OF ALEMTUZUMAB ON MRI ACTIVITY AND BRAIN ATROPHY IN RELAPSING-REMITTING MULTIPLE SCLEROSIS PATIENTS: 4-YEAR FOLLOW-UP OF CARE-MS IIAnthony Traboulsee,1 Hans-Peter Hartung,2 Eva Havrdova,3 Krzysztof W. Selmaj,4 D. Alastair S. Compston,5 David H. Margolin,6 Linda Kasten,7 Douglas L. Arnold8,9

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1040.04, SD 429.25) to posttest (mean 1190.73, SD 579.95); F = 6.35, P = .045. Conclusions: Subjects increased in maximal leg press strength, BBS scores, and 6MW distance following the MST intervention. The MST was well tolerated by all subjects. MST may provide an additional means of improving mobility in people with MS. Discerning the mechanism of its effectiveness requires further examination.

Disclosure: Herbert I. Karpatkin: Acorda Therapeutics (speakers’ bureau). David Park, Sarah Dworetsky, Charlie Wright, Michael Zervas: Nothing to disclose.Keywords: Resistance training, Gait, Balance

(RH02) IMPACT OF A HOME-BASED EXERCISE INTERVENTION ON FITNESS AND WALKING OUTCOMES IN PEOPLE WITH MULTIPLE SCLEROSIS: PRELIMINARY RESULTSRachel E. Klaren,1 Garett Griffith,2 Tracy Baynard,2 Robert W. Motl,1 Bo Fernhall2

1Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL; 2University of Illinois at Chicago, Chicago, IL

Background: Previous research has examined the effect of exer-cise training interventions on aerobic fitness and mobility disability in people with multiple sclerosis (MS). Of note, supervised exercise training in a center has improved aerobic fitness and walking out-comes, whereas unsupervised, home-based exercise programs have not yielded the same effect. Such home-based programs may have suffered from poor compliance with the exercise prescription. This may undermine the potential value of exercise for large numbers of people with MS who cannot undertake supervised, center-based exercise programs. Accordingly, home-based exercise programs that adopt strategies for maximizing compliance might present a novel and efficacious approach for improving aerobic fitness and walking outcomes. Objectives: We investigated the effects of a novel, home-based exercise intervention on aerobic fitness (ie, VO2peak) and walk-ing mobility (ie, Timed 25-Foot Walk [T25FW] and 6-Minute Walk [6MW]) in people with MS. Methods: 20 people with MS (mean age 45 ± 10.1 years, mean body-mass index [BMI] 25.9 ± 5 kg/m², 15 females) who had mild disability (median EDSS score 3.0) were randomly assigned to aerobic exercise (ie, cycle ergometry) or attention-control (stretching along with minimal muscle strengthening stimuli) conditions. Both conditions provided standardized exercise programs delivered over a 12-week period and undertaken in the participants’ homes. Participants in both groups further engaged in weekly, one-on-one video chats with a behavioral coach for maxi-mizing compliance. The exercise group performed 3 days/week of cycle ergometry, initially for 10 minutes/day at 40% VO2peak and progressing to 30 minutes/day at 60%VO2peak. The attention-control group performed 3 days/week of stretching exercises, beginning with one set of five different stretches and progressing to two sets of 10 stretches. Aerobic fitness (ie, VO2peak) was assessed using a maximal, incremental exercise test on a cycle ergometer, and walk-ing mobility was assessed using T25FW and 6MW before and after the 12-week period. Results: There were significant improvements in VO2peak, T25FW, and 6MW favoring the aerobic exercise condi-tion compared with the attention-control condition. The effect sizes were d = 0.39, 0.65, and 0.48 for VO2peak, T25FW, and 6MW, respectively. Conclusions: These preliminary data suggest that a home-based aerobic exercise intervention that maximizes compliance can be effective for increasing aerobic fitness and walking mobility in people with MS.

Supported by: National Multiple Sclerosis Society (RG 4702A1/2)Disclosure: Rachel E. Klaren, Garett Griffith, Tracy Baynard: Nothing to disclose. Robert W. Motl: Biogen, Acorda (consulting fees, grant/research sup-port); EMD Serono (fees for non-CME services from commercial interests or their agents). Bo Fernhall: Department of Homeland Security, Federal Emergency Management Agency, Assistance to Firefighters Grant Program, Gift of Hope Foundation, National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (grant/research support); Holcomb Hathaway, Human Kinetics (royalty).

mouse model of MS. Our objective was to investigate if variation in ApoA-I levels could alter disease progression. Methods: ApoA-I deficient female mice (C57Bl/6-Tg(ApoA1)1Rub/J) demonstrated a higher incidence and severity of EAE in comparison to the wild-type control mice (C57Bl/6J). EAE was accompanied by an increase in cytokines (INF-g, TNF-a, TGF-ß, IL-2, IL-23) and T-cell differen-tiation into CD25+/Foxp3+ T cells. Because ApoA-I levels can be modulated by liver X receptors (LXRs), we next tested whether the LXR agonist GW3965 and fenofibrate (a downregulator of ApoA-I in mice) altered EAE. Results: We found that mice treated with the oral agent GW3965 had a lower disease incidence, EAE scores, and cytokine expression compared to mice with standard EAE or animals treated with fenofibrate. Variation of ApoA-I levels correlated with disease incidence and severity. Further, GW3965 supplementation resulted in increased ApoA-I production in the liver and in the spinal cord of experimental animals. Conclusions: These data suggest that ApoA-I is a novel target for immune modulation by an oral medica-tion, which might be applicable to MS patients.

Supported by: UTHSC MS Research FundDisclosure: Nothing to discloseKeywords: Complementary/alternative therapies in MS, Disease-modifying treat-ments in MS, Immunology and MS

REHABILITATION

(RH01) EFFECTS OF MAXIMAL STRENGTH TRAINING ON GAIT AND BALANCE IN PEOPLE WITH MULTIPLE SCLEROSIS: A PILOT STUDYHerbert I. Karpatkin, David Park, Sarah Dworetsky, Charlie Wright, Michael Zervas

Physical Therapy, Hunter College, New York, NY

Background: Clinicians who treat gait and balance impairments in people with multiple sclerosis (MS) frequently utilize resistance train-ing. Typically, the type of resistance training done utilizes relatively low loads, with the implicit assumption that higher-intensity training may not be well tolerated due to neurogenic fatigue. Recent evi-dence has suggested that using maximal strength training (MST) in people with MS as well as other central nervous system disorders may actually offer a unique and effective means of improving gait and balance. However, the effect of MST on gait and balance in people with MS has not been examined. Objectives: The purpose of this study was to examine whether an MST program in people with MS would result in improvements in gait and balance measures. A secondary goal was to assess whether such a program will be well tolerated in this population. Methods: A single-group pretest-posttest design was used with 7 participants with mild MS. The exercise program entailed participants completing a twice-weekly program for 8 weeks in which they performed 4 sets of 4 repetitions of leg presses on each leg at a weight equal to 85% to 90% of their 1-repetition maximum (1RM). Data from the 6-Minute Walk (6MW) test, the Berg Balance Scale (BBS), and the 29-item Multiple Sclerosis Impact Scale (MSIS-29) were collected from participants at baseline and upon completion of the exercise program. Participants’ 1RM lift for a seated hip extension was also determined for the right and left legs at baseline and upon completion of the program. Results: Five females and 2 males with mild MS (mean EDSS 3.75) completed the study. None of the subjects reported any adverse effects. Results from a repeated-measures MANOVA with bootstrapping showed that participants’ maximal right leg press increased significantly from pretest (mean 146.07, SD 93.36) to posttest (mean 228.93, SD 95.98); F = 20.26, P = .004. Participants’ maximal left leg press also increased significantly from pretest (mean 142.86, SD 100.87) to posttest (mean 215.00, SD 114.07); F = 63.03, P < .001. BBS scores significantly improved from pretest (mean 44.29, SD 8.34) to posttest (mean 49.57, SD 5.83); F = 15.56, P = .008. Scores for the 6MW also showed significant increases from pretest (mean

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temporal discrepancies between actual and mental movements (anisochrony) could be an expression of neurologic deficits on action representation. In a previous study, taking into account actions executed as quickly and accurately as possible, we showed that in people with multiple sclerosis (MS), MI does not demonstrate isoch-rony as in healthy subjects (HS), with mental movements faster than actual actions. Objectives: Considering mental actions faster than the actual, we investigated whether MI could be used to speed move-ment execution (ME) in people with MS. Methods: 17 HS and 8 people with MS were recruited. They were seated in front of a table on which a sheet with two identical square targets was placed. They held a pen with the right hand and were initially positioned with the target on their left. During ME sessions, the subjects were requested to complete five actual cycles of pointing between the two targets as accurately and quickly as possible. During MI sessions, the first four cycles were mentally performed, whereas the fifth was actually executed. To calculate the differences between MI and ME, the time to complete the first four cycles was compared. To evaluate the effect of MI on ME, the fifth cycle in the two conditions was compared. The time was calculated placing on the pen tip a marker recorded by a camera’s BTS system. In each session, the size of the target randomly changed: 0.5 × 0.5, 1 × 1, 1.5 × 1.5, and 2 × 2 cm2. Results: During ME, HS and people with MS similarly modulated movement duration with the target size, increasing the speed with larger targets, although people with MS were slower. Moreover, no differences between ME and MI were found in HS, whereas in people with MS, MI was always faster than ME. More importantly, in people with MS, the fifth cycle was significantly faster during MI sessions than during ME sessions. Conclusions: This result seems to indicate that, when an imbalance between mental and actual execution of actions is present with mental movements faster, an effect of speeding of ME occurs. These results agreed with the hypothesis that MI, by recruiting the same motor neural structures involved during ME, could improve the ME. This result opens a new possibility in the field of neurore-habilitation in people with MS, who demonstrate mental and motor processes slower than those of HS and a related general decline of spatiotemporal characteristics.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Complementary/alternative therapies in MS, Mental imagery

(RH05) EXPLORATION OF TIMED UP AND GO SCORES WITH AND WITHOUT A COGNITIVE CHALLENGE IN PEOPLE WITH MULTIPLE SCLEROSIS AND A HEALTHY REFERENCE GROUPLaura E. Comber, Rachel Tierney, Susan B. Coote

Department of Clinical Therapies, University of Limerick, Limerick, Ireland

Background: The Timed Up and Go (TUG) test is a quick and easily administered test of dynamic mobility. It may be useful in iden-tifying those in need of rehabilitation interventions and distinguishing between fallers and nonfallers. Adding a cognitive challenge to the TUG may further enhance its usefulness. Objectives: 1) To evaluate whether the scores on the TUG and the TUG with a cognitive chal-lenge (TUG-C) differ between people with multiple sclerosis (MS) and a healthy reference group. 2) To evaluate the differences between the TUG and TUG-C scores for each of those groups. 3) To evaluate the difference in TUG and TUG-C scores between people with MS who do and do not report a fall in the past 3 months. Methods: A cross-sectional study that took place in a university, an MS society, and an outpatient neurology clinic. The average of three TUG walks and the average of three TUG walks while subtracting numbers in threes were analyzed. A faller was defined as a person with MS who reported one or more falls in the past 3 months. Results: 50 university students (mean age 22.7, range 18–40, 14 males, 36 females) were used as a healthy reference sample, and 28 people with MS (mean age 53.39, range 29–69, 7 males, 21 females)

Keywords: Complementary/alternative therapies in MS, Comprehensive care and MS, Management of activities of daily living in MS

(RH03) UTILIZING TECHNOLOGY TO IMPROVE PATIENT ADHERENCE AND PROFESSIONAL PATIENT MONITORING FOR AT-HOME EXERCISE PROGRAMS IN PATIENTS WITH MULTIPLE SCLEROSISHunter Vincent,1 Mary Ann Picone,2 Jason Kavountzis3

1Touro College of Osteopathic Medicine, New York, NY; 2Multiple Sclerosis, Holy Name Medical Center, Teaneck, NJ; 3Rehabilitation, Holy Name Medical Center, Teaneck, NJ

Background: Multiple sclerosis (MS) is a degenerative neurologic disorder that can present with a wide range of motor, sensory, and cognitive dysfunction, with significant symptom variance among indi-vidual patients. Patients are frequently confronted with many hurdles such as transportation issues and long distances to MS specialists, which make it difficult for patients to receive the highest-quality treat-ment and consistent monitoring. Although no cure has been identified for MS, exercise and physical rehabilitation programs have exhibited positive outcomes in patients’ quality of life, fatigue, motor function, and overall well-being. However, adherence with any rehabilita-tive program or exercise routine has often been very low, and is a limiting factor in maximizing the positive benefits of an appropriate exercise program. The use of technology could provide a method for improving patient compliance, while providing therapy to patients who would not otherwise be able to receive it. Objectives: This study proposes a protocol for a remote monitored telerehabilitation program for patients with MS. The study examines the effectiveness of technology, including the iPad and Fitbit exercise tracker, on improving overall physician-patient communication, access to physi-cal therapy programs, and patient compliance with prescribed reha-bilitation programs. Methods: The 8 patients selected for this case series met all inclusion and exclusion criteria and presented with dis-ease symptoms uniquely different from each other. Patients completed an in-person comprehensive initial consultation, including physical examination, baseline functional assessment via Tinetti balance assessment, Timed 25-Foot Walk, and Timed Up and Go test, as well as technical instruction on iPad FaceTime and Fitbit exercise tracker. Each patient was provided with an at-home exercise program, consisting of 8 to 10 exercises tailored toward their needs. Patients were instructed to wear their Fitbit every day and perform their rehab program 5 to all days. Patients also kept an exercise diary, noting the date and time of their exercises, as well as any concerns or diffi-culties. Each patient’s follow-ups were performed via FaceTime video call every 2 to 3 weeks to assess progress and discuss any necessary changes. Following completion of the 12-week program, all patients returned to the clinic for reassessment of baseline functional tests and completion of a poststudy questionnaire. Results: Pending. Conclu-sions: The utilization of iPad and Fitbit technology proved to be an effective method of conducting a remote monitored telerehabilitation program for MS patients. FaceTime video calls and Fitbit exercise trackers improved patient compliance with at-home rehab programs, as well as patient-physician communication.Supported by: NoneDisclosure: Nothing to discloseKeywords: Complementary/alternative therapies in MS, Management of activi-ties of daily living in MS, Rehabilitation

(RH04) MENTALLY SIMULATED MOTOR ACTIONS IN NEUROREHABILITATION: A PILOT STUDY IN MULTIPLE SCLEROSISAndrea Tacchino,1 Mario Alberto Battaglia,2 Marco Bove,3 Ludovico Pedullà,1,3 Giampaolo Brichetto1

1Scientific Research Area, Italian MS Society, Genoa, Italy; 2Department of Life Science, University of Siena, Siena, Italy; 3Department of Experimental Medicine, Section of Human Physiology, University of Genoa, Genoa, Italy

Background: Motor imagery (MI) is defined as mental movement execution without any actual movement. Mental movement time in healthy adults is similar to actual movement time (isochrony), while

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ability. Methods: Twenty-one female and 8 male MS patients were randomly assigned to RRMT (13 women, 1 man) or placebo control (8 women, 7 men) groups. All patients had EDSS scores between 1.0 and 6.0, and were able to pedal a cycle ergometer continuously for 10 minutes. They were nonsmokers and had not had a relapse or new steroid use in the last 6 weeks or a recent respiratory infection. Ages were 51.1 ± 13.3 years (RRMT) and 48.6 ± 12.8 years (C). Average Expanded Disability Status Scale (EDSS) scores were 3.1 ± 1.9 (RRMT) and 2.9 ± 1.8 (C). Average years since diagnosis were 12.5 ± 7.0 (RRMT) and 15.4 ± 11.6 (C). The measurements of maximal inspiratory (PImax) and expiratory (PEmax) pressures (Viasys metabolic system) and self-reported fatigue (Modified Fatigue Impact Scale; MFIS), as well as exercise time to voluntary exhaustion at 60% of peak workload on a cycle ergometer, were conducted before and after 6 weeks of the intervention. The RRMT and placebo control (no load) breathing were conducted 3 times per week, 30 minutes per session, using a specially designed device that measured inspira-tory and expiratory pressures on each breath. Resistances for RRMT progressively increased from 30% to 80% of the initial maximal inspiratory and expiratory pressures over the 6 weeks. The patients completed one session in the lab and then two sessions at home each week. T tests were used to analyze the changes from before to after the intervention. Results: The RRMT group had significant improve-ments in PImax (P = .0037; 77.3 ± 31.2 to 97.5 ± 28.0 cm H2O), PEmax (P = .0020; 74.6 ± 22.5 to 97.6 ± 25.6 cm H2O), MFIS physi-cal fatigue (P = .0022; 16.6 ± 8.8 to 12.5 ± 7.2), MFIS total fatigue (P = .0125; 33.7 ± 15.4 to 26.2 ± 16.4), and exercise duration (P = .0295; 24.2 ± 15.4 to 31.7 ± 25.5 min) from pre- to post-inter-vention. The placebo control group did not have significant changes in any of the physical measures. Conclusions: A 6-week RRMT pro-gram of the inspiratory and expiratory muscles improves respiratory muscle strength, exercise endurance, and perceived fatigue in MS patients with mild-to-moderate disability.

Supported by: National Institute on Disability and Rehabilitation Research (grant H133G120081)Disclosure: Nothing to discloseKeywords: Resistive respiratory muscle training and MS

also took part. The mean TUG score for the reference group (REF) was 5.8 ± 0.8 and for the MS group was 13.4 ± 8.6; these were statistically different using nonparametric statistics (P < .01). The mean TUG-C scores were also statistically different (REF 6.0 ± 1.0, MS 17.3 ± 11.9, P < .01). There was a significant difference between the TUG and TUG-C scores for the REF (0.2 ± 0.5, P = .02) and the MS groups (3.9 ± 7.6, P < .001). Seven people reported a fall in the previous 3 months; their TUG score (13.5 ± 5.6) was not significantly different from that of the nonfallers (n = 21, 13.4 ± 9.5, P = .640). Similarly, there was no difference between fallers and nonfallers for the TUG-C (P = .836). Conclusions: People with MS have significantly slower TUG and TUG-C scores compared to a healthy reference group. While the mean differences between TUG and TUG-C are significant for both groups, the absolute differences are much larger for the MS cohort. There was no difference between fallers and nonfallers, but this requires confirmation using prospective monitoring of falls status.

Supported by: University of LimerickDisclosure: Laura E. Comber: University of Limerick (grant/research support). Rachel Tierney, Susan B. Coote: Nothing to disclose.Keywords: Falls

(RH06) RESISTIVE RESPIRATORY MUSCLE TRAINING INCREASES RESPIRATORY MUSCLE STRENGTH AND EXERCISE ENDURANCE, AND REDUCES FATIGUE IN MULTIPLE SCLEROSISNadine M. Fisher, Andrew D. Ray

Rehabilitation Science, University at Buffalo, Buffalo, NY

Background: Respiratory muscle weakness and fatigue in normal individuals can lead to reduced exercise performance due to the diverting of blood from the peripheral muscles to the respiratory muscles during activity. Resistive respiratory muscle training (RRMT) has been shown to improve respiratory and locomotor performance; however, its effects in multiple sclerosis (MS) patients have not been examined. Objectives: The objective of this study was to determine the effects of 6 weeks of RRMT on respiratory muscle strength, exer-cise endurance, and fatigue in MS patients with mild-to-moderate dis-

IJMSC Now in PubMed Central and PubMedThe International Journal of MS Care (IJMSC) now participates in PubMed Central (PMC), a free electronic archive of

full-text biomedical and life sciences journal literature at the US National Institutes of Health’s National Library of Medi-cine (NLM). Newly published articles can be accessed in PMC soon after publication, along with older articles going back to 2011. Citations and abstracts of these articles are retrievable in PubMed, the NLM’s journal abstract database (which includes the MEDLINE subset), through various types of searches.

PMC, which launched in 2000, serves as a digital counterpart to the NLM’s print journal collection. It is a repository for journal literature deposited by participating publishers, as well as for author manuscripts that have been submitted in compliance with the NIH Public Access Policy and similar policies of other research funding agencies. Currently, more than 3 million articles from over 5000 journals are archived in PMC.

The availability of IJMSC content in PMC and PubMed will make it more discoverable to researchers, health profes-sionals, and the public. Each IJMSC search result in PubMed contains a link to the full-text article. This increased visibility and accessibility should lead to wider citation of IJMSC articles, helping to advance research and clinical practice in multiple sclerosis. Copyright to IJMSC material deposited in PMC remains with the Consortium of Multiple Sclerosis Centers, which is clearly indicated to PMC users.

In addition to being available in PMC and PubMed, IJMSC is indexed in the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Rehabilitation & Sports Medicine Source (EBSCO Publishing), as well as Scopus.

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Posters: Comprehensive Care

POSTERS

COMPREHENSIVE CARE

(CC07) HEALTH-CARE REFORM IN THE UNITED STATES OFFERS OPPORTUNITY TO THE CONSORTIUM OF MULTIPLE SCLEROSIS CENTERSJohn P. Conomy, MD, JD

Neurology, Case Western Reserve University, Cleveland, OH

Current formalization of health-care reform in the United States is embodied in the Affordable Care Act (ACA) passed by Congress in 2010 and the determination of constitutionality of the act found by the US Supreme Court in 2012. Preceding and following these actions, the content and progress of health-care reform in the United States has been marked by rancorous debate, unremitting and so far unsuccessful legislative and legal assaults, and intense public debate with social and political divisiveness and public incivility. Yet the ACA, popularly denoted by the term “Obamacare,” is the law of the land. Popular and political reaction to the ACA has been characterized by intense public polarization, and focused on opera-tional shortcomings and fundamental ideology. The ACA itself owes its genesis to more than political promise. The United States simply could not, as a matter of urgent practicality, afford the national cost of medical care, approaching nearly $3 trillion, and on its seemingly unstoppable way to 20% of national GDP, simultaneously leaving about 50 million US residents without effective access to health care. As a moral matter, the ACA continues the nation’s undone human rights mission. To date, about 13 million people have signed onto insurance exchanges to enroll in ACA-derived medical care, and 7 million have completed that enrollment. As a matter of political necessity, the ACA incorporates the traditional role of the medical insurance industry, and the role of states to deny, by legislative fiat, expansion of family care under Medicaid. Many states choosing the latter route are among the poorest and least healthy in the United States. The opportunity arises for the Consortium of Multiple Sclero-sis Centers (CMSC) and organizations like it to act with expanded effect in taking a prominent role in how health care for a nation is reshaped—organizations built around demonstrably effective roles in the organization of outpatient-based, multidisciplinary care that integrate missions encompassing patient care, research, and educa-tion directed at those suffering from chronic, disabling illnesses. To effectively accomplish this, such organizations need to establish facil-ity independence, strengthen the bonds of relatedness among mission elements, seek the advice of related organizations on an interna-tional level, support national global medical budgeting, and, joining with the patients and their families, present their case to government, the public, and national funding sources that must be persuaded to understand the quality, outcome, and cost issues improved by the provision of comprehensive care.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Comprehensive care and MS

(CC08) NEW PATIENT TRIAGE FOR OUT-OF-STATE MULTIPLE SCLEROSIS PATIENTSClaire Hara-Cleaver, Alissa Willis

Mellen Center, Cleveland Clinic, Cleveland, OH

Background: Patients with multiple sclerosis (MS) often have a vari-ety of needs in addition to recommendations for disease-modifying therapy. A coordinated team approach is often the most efficient and effective way of addressing these complex needs, but this approach is challenging to implement for patients who travel long distances for their care. A new patient triage program incorporating a pre-travel consultation with an advanced practice nurse was established to facilitate care coordination for patients traveling from out of state.

Objectives: Describe a new model of care for MS patients referred from out of state for this MS care. Methods: Out-of-state patients who had never been seen at our institution were given the option of scheduling a phone consultation with an advanced practice nurse prior to making travel arrangements. All patients electing to have this phone consultation were scheduled within 7 days of their initial contact with the scheduling office. The date of the phone consulta-tion, distance from the clinic, date of neurology consultation, recom-mendation for other services, and scheduling of other services were systematically tracked. Patients were asked to complete a satisfaction survey retrospectively. Results: In the 1-year pilot of this new patient triaging program, 102 telephone consultations were completed. Seventy-three patients completed their trips to our institution, and 25 patients had visits coordinated with one or more services. The most common coordinated visits included neurology, physiatry/rehabilita-tion, and physical therapy. Patients came from an average of 529 miles from our facility, with 37% traveling more than 500 miles. Collection of patient satisfaction scores is ongoing. Conclusions: This pilot project demonstrated improved coordination of care for MS patients through a brief phone consultation with an experienced MS clinician prior to the initial visit. This consultation identified patient expectations prior to the visit and facilitated access to other specialty care resources. Patient and health-care provider perceptions and cost-effectiveness will be explored further.

Supported by: NoneDisclosure: Claire Hara-Cleaver: Biogen Idec, Genzyme, Novartis, Teva (con-sulting fees). Alissa Willis: Biogen Idec, Genzyme (consulting fees).Keywords: Comprehensive care and MS, Nursing management in MS

(CC09) EDSS: TO WALK OR NOT TO WALK? ASSESSING THE RELIABILITY OF PATIENTS TO SELF-REPORT THEIR AMBULATION DISTANCE PRIOR TO MEASURING ACTUAL DISTANCE WALKEDJacob (Jake) Reznik, Marcie Weiss, Kayla McGowan, Calvin Mok, Tara Martin, Jill R. Nelson, Elliott Weiss, Galina Vorobeychik

Fraser Health Multiple Sclerosis Clinic, Burnaby, BC, Canada

Background: The most commonly used disability scale in patients with multiple sclerosis (MS) is the Expanded Disability Status Scale (EDSS), which was developed by Kurtzke in 1983. EDSS scores of 5.0 to 8.0 are predominantly associated with impairment in ambula-tion. It is common in clinical practice to replace a walking test with self-reported patient information on ability to walk, especially for patients who are able to walk more than 100 m. There is little infor-mation published about the reliability of using such an approach and factors affecting it. Objectives: 1) To establish correlation between subjective walk (SW, self-reported patient ability to walk) and objec-tively walked distance under supervision of trained provider (OW). 2) To analyze impact of different cognitive factors on this correlation. Methods: We randomly selected 30 MS patients (20 females, 10 males, with average age 47 ± 7 years) with varying degrees of disability. Per clinical practice, each patient was assessed for depres-sion, anxiety, fatigue, and cognition, and administered the 25-Foot Walk as well as reported SW and Patient-Determined Disease Steps (PDDS) prior to walking up to 500 m under supervision of a trained provider (OW). Results: We excluded 3 patients from the 30, who were unable to estimate SW but able to walk 100 to 400 m. Among 18 patients with SW of 500 m or more, 3 (17%) were not able to walk farther than 300 m. The PDDS was between 2 and 3 for these patients. Among 9 patients with SW less than 500 m, 7 (78%) were able to walk 100 m more than they reported, which affects EDSS. Of these 7 patients, PDDS was between 3 and 5, and none had severe cognitive impairment, depression, anxiety, or fatigue. Conclusions: Patient self-reported ability to walk differs from actually measured ability in some patients (17%) who have reasonably preserved ambu-lation, and in the majority of patients (78%) with limited ambulation. These data reinforce proper technique of measuring ambulation with a trained supervised provider to obtain accurate EDSS scores. We

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and safety. Treatment efficacy and safety depend on adherence. Adherence measures rely on direct observation, self-report, and pharmacy records (medication retention, refill frequency). Morisky Medication Adherence (MMA) questionnaires have been extensively studied for analysis of adherence to treatment in multiple disease states. Predicted adherence has also been correlated with clinical out-comes and disease costs. MS, a chronic condition, requires chronic treatment adherence. The magnitude of nonadherence is unclear. Objectives: To investigate the RRMS population adherence pro-file. Methods: Single-site, cross-sectional retrospective analysis of people with RRMS who completed a validated standardized questionnaire in routine clinical care. Adherence was evalu-ated by a 4-point questionnaire. Morisky Medication Adherence Scores (MMAS-4) define adherence: high, medium, and low. Results: 272 RRMS patients over 11 months (2012–2013) com-pleted the MMAS-4: 83% female, average age ~50 years, 21% no DMT/between DMT, 4% oral DMT, 26% injectable DMT, 49% infusion DMT. 237 of 272 (87.13%) high adherence, 35 of 272 (12.87%) medium adherence, and no low adherence (MMAS-4). Conclusions: The RRMS population reflects 13% medium and 87% high adherence. The literature and clinical experience suggest that suboptimal adherence to prescribed DMT may be more common. Analysis of nonadherence in the RRMS population needs further exploration. Poor adherence can affect care, choice of DMT, and the efficacy and safety of the DMT chosen. Understanding predictors of adherence is important.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Comprehensive care and MS, Economic issues and MS, Nursing management in MS

(CC12) DYSEQUILIBRIOCEPTION (IMBALANCE) IN MULTIPLE SCLEROSIS: CAN DYNAVISION D2 VISUOMOTOR TRAINING SYSTEM BE AN EFFECTIVE TOOL FOR THE MEASUREMENT OF BALANCE?Marcie Weiss, Kayla McGowan, Calvin Mok, Elliott Weiss, Galina Vorobeychik


Background: Imbalance is a common clinical finding in multiple sclerosis (MS) and can be caused by visual, perceptual, vestibular, and/or proprioceptive deficits. It is one of the major sources of physi-cal disability. One of the major tools used to measure balance is the Berg Balance Test (BBT). Dynavision D2 is a computerized tool that systematically records responses to variable visual stimuli. However, its value in indirectly measuring balance and correlation with the BBT has not been described in an MS population. Objectives: To determine the relationship between BBT scores and Dynavision D2 as related to the assessment of balance in an MS outpatient population. Methods: Twenty-nine patients were selected from an outpatient MS clinic population. They underwent BBT testing and subsequently a Dynavision D2 assessment. They were separated into two groups, with the first group (15 patients) performing two trials, one with each hand, and the second group (14 patients) performing one trial using both hands. The goal was to turn off as many lights as pos-sible during a 60-second timed period. Results: The results show a significant correlation between BBT and Dynavision D2 only when using the right hand (P = .0279) to turn off the lights. There was no significant correlation between the BBT and Dynavision D2 for the left hand (P = .132) and using both hands (P = .666). The majority of the patients tested (21) were right-handed, 2 were left-handed, and 5 were unknown. Conclusions: The Dynavision D2 may be a useful objective computerized tool to indirectly measure equilibrioception in an MS population, especially when using the right (dominant) hand. More research is needed to determine the full utility of Dynavision D2 as a measurement of balance.

Supported by: Fraser Health Multiple Sclerosis ClinicDisclosure: Nothing to discloseKeywords: Comprehensive care and MS, Equipment in MS

were unable to determine impact of depression, anxiety, fatigue, cog-nition, 25-Foot Walk, and reported SW and PDDS on self-reported bias. Additional studies with larger numbers of patients will be needed to confirm our results and to analyze the impact of the above-mentioned factors.

Supported by: Western-Pacific endMS Summer Studentship Award from the Multiple Sclerosis Society of Canada and the Multiple Sclerosis Scientific Research FoundationDisclosure: Nothing to discloseKeywords: Comprehensive care and MS, Epidemiology of MS

(CC10) ROLE OF INTERDISCIPLINARY TEAM IN MANAGING CAREGIVER’S STRESSJitender Kalra

Medical Specialty Clinic, Red Deer Regional Hospital Centre, Alberta Health Services, Red Deer, AB, Canada

Caregiver’s stress (Buhse M, J Neurosci Nurs. 2008;40[1]) is a burden that a caregiver faces while providing necessary care tasks to the family member with multiple sclerosis (MS). It can be physical, psychological, emotional, social, and financial. It is both objective and perceived. The perceived burden has a direct correlation with risks of depression and lower quality of life. It has been documented in various studies that almost half of caregivers experience clinical depression; 61% of intense family caregivers experience depression (Haley LaMonde et al., 2001; Pochard et al., 2001; Rabow et al.). It is important to provide timely intervention by diagnosing it early. Following are the tools to assess caregiver’s stress: 1) CAREQOL-MS, 2) Zarit Caregiver’s Burden Interview, 3) Kingston Caregiver’s Stress Scale, 4) SF-36. Management consists of the following: Interdisciplin-ary team approach to address caregiver’s burden (physician, RN, SW, RD, and OT); education about caregiver’s task skills pertaining to caregiving/proper techniques; education regarding manage-ment of symptoms/side effects/new research/medications; stress management; teaching about warning signs of burden; counseling services; increase socialization/social participation; community sup-port group. Using a case study, we are able to conclude that the interdisciplinary team approach plays an instrumental role in manag-ing caregiver’s stress and improving quality of life for both caregiver and patient.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Management of activities of daily living in MS, MS and the care-giver/family, Psychological issues and MS

(CC11) MULTIPLE SCLEROSIS AND ADHERENCE: A COMMUNITY-BASED ANALYSIS OF A PROBLEM IN MS CAREMark Gudesblatt,1 Shenira Cherry,2 Barbara Bumstead,1 Myassar Zarif,1 Lori Fafard,1 Smitha Thotam,1 Karl Wissemann,1 Cynthia Sullivan,3 Jeffrey Wilken,3 Marijean Buhse,1,4 Donald E. Morisky5

1South Shore Neurologic Associates, Patchogue, NY; 2The Chicago School of Professional Psychology, Washington, DC; 3Neuropsychology Associates of Fairfax, LLC, Fairfax, VA; 4School of Nursing, State University of New York at Stony Brook, Stony Brook, NY; 5Department of Community Health Sciences, UCLA School of Public Health, Los Angeles, CA

Background: Multiple sclerosis (MS) can cause significant disabil-ity. Many disease-modifying therapies (DMTs) are approved to treat relapsing MS (RRMS). DMTs vary in route and frequency of required administration. Adherence affects DMT efficacy. Suboptimal inject-able DMT adherence (<75% at 1–2 years) and oral DMT safety mon-itoring adherence (<75%) are reported. Identifying low adherence in patients is critical. Treatment adherence may be important but not considered related to MS DMT choice or efficacy. Multiple factors affect prescribed DMT adherence. Identifying and addressing factors that affect adherence may improve outcome. Exploring nonadher-ence magnitude may improve awareness of this issue. The economic impact of MS is related to many factors (unemployment, disability, and DMT cost). These costs demand high adherence, high efficacy,

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basis for developing “best practices” for ITB for severe spasticity. The online survey was deployed in 2013 to 42 physicians (21 neurolo-gists, 21 physical medicine and rehabilitation physicians) recruited by an expert panel. Participants had been in practice for >2 years, spent >50% of their time in direct patient care, and currently man-aged >25 ITB patients being treated for cerebral palsy, brain injury, stroke, multiple sclerosis (MS), or spinal cord injury. Results: Patients were pediatric (19%), adult (66%), or geriatric (15%). Physicians always/often used deep tendon reflexes (95%), Manual Muscle Test (84%), and Ashworth/Modified Ashworth Score (83%) to assess spasticity. ITB was generally offered after one or more other thera-pies had failed. Spasticity interfering with comfort, function, and/or caregiving was the main criterion (95%) for considering ITB therapy. Goals included improved quality of life (88%), reduced spasticity (88%), increased comfort (81%), reduced pain (81%), and improved active function (79%). 69% used a screening test to demonstrate efficacy and assess patient/caregiver interest in ITB. Before screen-ing, oral antispasmodics were maintained 49% of the time versus tapering (36%) or weaning (15%). Patient responses were measured at baseline (68%), 1 hour (60%), 2 hours (68%), 3 hours (35%), and 4 hours (60%). Screening results, starting dose, cause of spasticity, and catheter tip placement were reported to the implanter after a suc-cessful trial. There was great variation in timing of postoperative dose titration and in oral medication weaning. Average minimum doses ranged from 100 to 170 µg/day for adults and 50 to 125 µg/day for children, with maximum doses varying by diagnosis. Con-tinuous mode dosing was used in 59% of patients; flex dosing was most common for predictable spasticity patterns. Physicians strongly concurred in sharing emergency information (overdose, underdose, withdrawal, after-hours contact and procedures, manufacturer emer-gency card) with patients. Loss of ITB efficacy was the most common problem requiring troubleshooting. Equipment problems most often involved catheters or off-schedule dosing/refill issues. The majority of physicians started troubleshooting by collecting a comprehensive patient history (74%) and interrogating the pump (71%). ITB with-drawal was treated most often/always with oral baclofen (71%) or benzodiazepines (43%). 81% of the physicians used an EMR, and two-thirds reported their emergency department had access to it. Conclusions: Consensus was clear on key metrics, practices, and protocols. Dosing and therapy management were tailored to indi-vidual patients and thus more variable.

Supported by: MedtronicDisclosure: Michael Saulino: Independent Blue Cross (consulting fees); Jazz Pharmaceuticals, Medtronic (grant/research support, speaking fees); Mallinckrodt (grant/research support); SPR Therapeutics (advisor fees). Aaron Boster: Jazz Pharmaceuticals, Mallinckrodt (grant/research support); Medtronic (consulting fees); Novartis (speaking fees).Keywords: Comprehensive care and MS, Equipment in MS, Intrathecal baclofen

(CC15) A QUALITATIVE SURVEY OF BEST PRACTICES IN INTRATHECAL BACLOFEN THERAPYAaron Boster,1 Michael Saulino2

1Neurology, The Ohio State University Wexner Medical Center, Columbus, OH; 2MossRehab, Elkins Park, PA

Background: A qualitative survey was designed to summarize points of consensus and divergence related to best practices in intra-thecal baclofen (ITB) therapy for severe spasticity. Objectives: To provide clinical guidance leading to favorable long-term outcomes. Methods: The panel consisted of 22 practitioners (20 physicians, 1 nurse practitioner, 1 physical therapist) practicing for a mean of 13 years (range 6–20 years), treating 23% pediatric versus 77% adult patients primarily for cerebral palsy, cerebrovascular accident, multiple sclerosis (MS), or spinal cord or traumatic brain injuries. Results: Patient Selection: An appropriate candidate for ITB has severe generalized spasticity that negatively affects quality of life (eg, function, movement, sleep, comfort). Nearly half of participants say that a patient must have tried at least one oral therapy before ITB

(CC13) BEST PRACTICES IN INTRATHECAL BACLOFEN THERAPY: DOSING AND LONG-TERM MANAGEMENTMichael Saulino,1 Mark Gudesblatt2

1MossRehab, Elkins Park, PA; 2South Shore Neurologic Associates, Patchogue, NY

Background: Intrathecal baclofen (ITB) therapy aims to reduce spasticity and provide functional control. Objectives: To manage ITB dosing and therapy. Methods: An expert panel consulted on best practices. Results: Pump fill and drug delivery can be started intraoperatively. For new/replacement pumps, a pre-implant priming bolus should be given. After implant, priming of the catheter only will quickly advance the drug to the tip. Monitor the patient for at least 8 hours. Initiate with the 500 µg/mL concentration to maximize dos-ing flexibility in the lower range. The starting daily dose should be twice the effective bolus screening dose, or the screening dose if the patient had a prolonged response (>8 hours) or negative reactions. In tenuous cases, ITB can be started at a minimum rate and increased when the patient is stable. Oral antispasmodics can be weaned, one drug at a time, beginning with oral baclofen, after ITB begins. Oral baclofen doses can be decreased by 25% to 50% at one time. Assess within 24 hours of a dose change. Have oral baclofen avail-able during titration and for management of ITB withdrawal. For adults, daily dose increases may be 5% to 15% once every 24 hours for cerebral origin spasticity and 10% to 30% once every 24 hours for spinal origin spasticity. Daily dose increases can be 5% to 15% once in 24 hours for children. At lower doses, the higher increases are reasonable, but at higher doses an increase of >20% may be excessive. Assess response at least every 24 hours for inpatients, who should receive intense, goal-directed rehabilitation. Outpatient adjustments can happen weekly, biweekly, or daily, depending on the patient’s ability to return. Step dosing (constant daily dosing for a set number of days before starting a higher continuous dose) can be used for patients who cannot return as often, but should be used cautiously in patients who use tone for function. Regular evaluation includes subjective, objective, and therapy goal measurements. Dosing options include simple continuous, variable 24-hour cycle or regularly scheduled boluses. Patients/caregivers should under-stand the treatment options, goals, and responsibilities, including follow-up and possible side effects (eg, over- and under-dose). Low reservoir alarm dates and refill schedules should be written down, along with emergency contact information. A higher concentration can be used at refill to extend refill intervals. A bridge bolus must be programmed, after which the pump will automatically adjust the new flow rate. Time changes may affect flex dosing. The SynchroMed II should be checked after MRI exposure. Pump replacement should be scheduled 3 to 6 months before the replacement interval. In sus-pected catheter malfunctions, ITB should be weaned preoperatively. In verified malfunctions, the dose should be reduced to the starting dose before revision surgery. Conclusions: ITB dosing is multistep and individualized.

Supported by: MedtronicDisclosure: Michael Saulino: Independent Blue Cross (consulting fees); Jazz Pharmaceuticals, Medtronic (grant/research support, speaking fees); Mallinckrodt (grant/research support); SPR Therapeutics (advisor fees). Mark Gudesblatt: Auspex, Biogen, EMD, Genzyme, Lundbeck, Medtronic, Novartis, Serono, Teva (consulting fees).Keywords: Comprehensive care and MS, Equipment in MS, Intrathecal baclofen

(CC14) A QUANTITATIVE SURVEY OF PRACTICES IN INTRATHECAL BACLOFEN THERAPYMichael Saulino,1 Aaron Boster2

1MossRehab, Elkins Park, PA; 2Neurology, The Ohio State University Wexner Medical Center, Columbus, OH

Background: Standard practices for intrathecal baclofen (ITB) therapy were surveyed as the basis for developing consensus on best practices. Objectives: To survey standard practices for current ITB therapy. Methods: A survey assessed standard practice as the

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their need for information and support both directly from health-care professionals and from a parent. Adequate information, provided with receptiveness, creates a base for the individual as well as for the family to cope with the situation. Well-informed parents can support their children and contribute to an atmosphere where questions are easier to raise. Conclusions: Health-care professionals need to pay attention to children as patients’ next of kin. Not only the children would benefit, but so would their parents, as their worries for their children would be reduced. Staff can be advised to pay attention to the parenting role, as parents may need reassurance and can benefit from advice about how to talk to their children about their condition and its impact on family life.

Supported by: Neuro Sweden and Research Committee, Örebro County CouncilDisclosure: Nothing to discloseKeywords: MS and the caregiver/family, Nursing management in MS, Psycho-logical issues and MS

(CC17) EXPLORING PATIENTS’ KNOWLEDGE AND MISCONCEPTIONS ABOUT MULTIPLE SCLEROSIS AND PREGNANCYSarah F. Wesley,1 Michelle Fabian,2 Stephen Krieger2

1Department of Neurology, Mount Sinai Beth Israel, New York, NY; 2Icahn School of Medicine, Corinne Goldsmith Dickinson Center for Multiple Sclerosis, New York, NY

Background: Multiple sclerosis (MS) has a high incidence in women of childbearing age, and accurate knowledge and under-standing of family planning issues is crucial for best outcomes. Objectives: To delineate which misconceptions might exist within the female MS population with regard to family planning, preg-nancy, breastfeeding, MS genetics, and medication safety through a pilot study. Methods: 37 female patients with MS aged 18 to 50 completed an anonymous questionnaire at a single MS center in New York. We collected baseline demographic information and reproduction history, and then asked 22 questions pertaining to four main categories: the effect of pregnancy on MS, the effect of MS on pregnancy, MS medication safety during pregnancy and breastfeed-ing, and the effect of MS on offspring. After completing the question-naire, patients were given an educational answer key. Results: The mean age of patients was 36 years (SD 5.6); 86% had relapsing-remitting MS (RRMS). The mean time since diagnosis was 6.7 years (SD 5.2), and 30.5% had been pregnant since their MS diagnosis. The average correct score on the questionnaire was 32.8% overall and 40.5% in patients who had been pregnant since MS diagnosis. The four main categories of knowledge were subanalyzed for cor-rectness. The largest area of deficit pertained to the effect of MS on reproduction, with an average of 27.7% correct. On questions pertaining to medication safety, the average percent correct was 35.9%. Only 21.0% knew that relapses can be treated with steroids during pregnancy; 50.0% of patients who had been pregnant knew this. Only 37.8% answered correctly a question on the importance of birth control while on disease-modifying drugs (DMTs). Furthermore, of the patients on DMTs, 34.0% reported not consistently using any form of birth control. Conclusions: There remain substantial unmet educational needs pertaining to reproductive issues in women with MS. Our data identified misconceptions on important topics and impact on patient behavior, including low awareness of the need for birth control while on DMTs and concurrently low self-report of effec-tive use of contraception. Education on this topic could help prevent adverse fetal outcomes. Additionally, patients’ misperceptions of neg-ative effects of MS on reproduction might make them disinclined to start families. We intend to replicate this study in a broad geographic cohort in order to plan educational initiatives to address these needs.

Disclosure: Sarah F. Wesley, Michelle Fabian: Nothing to disclose. Stephen Krieger: Acorda, Bayer HealthCare, Biogen Idec, EMD Serono, Genzyme, Quest-cor, Teva Neuroscience (consulting fees).Keywords: Comprehensive care and MS, Patient education

consideration. An unreliable patient with compliance issues should not be considered. Patient/caregiver education is vital. Screening Test: This determines efficacy and previews pump effects for the patient/caregivers. During screening patients are monitored for spas-ticity, vital signs, functionality, symptomatic hypotension, tachycardia, or desaturation. Patients are referred to an implanter after positive screening, and pump size, catheter tip location, and starting dose communicated. Key measures include function (tone, strength, range of motion, walking ability, stretching, Modified Ashworth Scores). Dosing and Therapy Management: Dose titration is most often started in an inpatient setting, with length of stay lasting 2 to 5 days. ITB doses for adults range from 25 to 100 µg, with dosing changes made according to response as patients are tapered off oral medica-tions starting with baclofen. The optimal ITB dose allows the patient to reach predefined, individual therapy goals. Patient education is reinforced verbally and in writing. Troubleshooting: Symptomatic patients (overdose or underdose) usually go to the emergency depart-ment or use oral baclofen and visit their doctor the next day. The Medtronic overdose/underdose algorithm is a key resource. First steps are an x-ray to check for catheter problems and trying a bolus dose. A careful patient history may also elicit non-pump problems. Acute underdose/withdrawal should be assessed in the hospital where ITB withdrawal can be managed. Preoperative dose tapering precedes pump revision. Participants encouraged strong collabora-tion in managing patient data (alarm dates, follow-up, diagnostic groups, dosages, outcomes), loss of efficacy, and complications, and in reviewing protocols. Conclusions: Participants recommended follow-up quantitative research to close information gaps and build on these findings.

Supported by: MedtronicDisclosure: Aaron Boster: Jazz Pharmaceuticals, Mallinckrodt (grant/research support); Medtronic (consulting fees); Novartis (speaking fees). Michael Saulino: Independent Blue Cross (consulting fees); Jazz Pharmaceuticals, Medtronic (grant/research support, speaking fees); Mallinckrodt (grant/research support); SPR Therapeutics (advisor fees).Keywords: Comprehensive care and MS, Equipment in MS, Intrathecal baclofen

(CC16) PATIENTS, PARTNERS, AND CHILDREN’S EXPERIENCES RELATED TO NEED FOR SUPPORT AND INFORMATION WHEN A PARENT IS DIAGNOSED WITH MULTIPLE SCLEROSISKatrin Å Boström, Ylva Nilsagård

Faculty of Medicine and Health, Örebro, Sweden

Background: A chronic neurologic disease like multiple sclerosis (MS), which debuts in the years when individuals are most likely to be parents of dependent children, affects the whole family and has a substantial impact on the children. Traditionally, health-care professionals focus solely on the patient, although there is a need to be aware of a child’s special needs when a parent is diagnosed with MS. Research has mainly explored the impact of a parent’s disease on children. Knowledge of what kind of support and suitable interventions these children and their parents need are thus limited. Objectives: The aim was to gain an understanding of how health care can support empowerment in children when a parent is diag-nosed with MS. The study explores needs and desires when a parent is diagnosed with MS from a triple perspective: the ill parent, the healthy parent, and the children. Questions about what they expe-rienced as important issues to acknowledge and act on to make it easier for a child to cope were raised. Methods: A qualitative study design using content analysis with an inductive approach was used. Nine focus group interviews were conducted with ill parents, healthy parents, and children separately. Results: The results describe how parents with MS, their partners, and their children regard their need for information and support. They jointly indicated the need to recognize all family members, as one member’s illness affects them all. Both ill and healthy parents wanted support from health-care professionals in addressing their children’s needs. Children described

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increased accountability, accomplishment, growth, and special-ized knowledge. There is an increased level of recognition among employers, peers, and consumers. Certification for nurses involved in multiple sclerosis (MS) care was established in 2002 by the Inter-national Organization of Multiple Sclerosis Nurses (IOMSN). The IOMSN recognized the need for MS nurses to meet the standards for MS nursing and recognize those who have demonstrated knowl-edge, skills, and expertise. The MS Nurses International Certification Board (MSNICB) was developed to enhance professional practice and patient care through MS nursing certification. The objectives of the MSNICB are to set the criteria for certification qualification and to develop, administer, and evaluate the examination for certifica-tion of nurses involved in MS patient/family care. Nurses who suc-cessfully pass the exam are able to call themselves an MS certified nurse (MSCN). Although certification is endorsed by the IOMSN, the perceived value of certification is the major influence on the decision of registered nurses to pursue the MS credentialing process. Objec-tives: The purpose of this study is to determine the perceived value of MS certification by nurses who are MSCNs. Methods: Working with the Professional Testing Corporation, all MSCNs who were certi-fied through November 2014 (n = 680) were e-mailed a survey that included demographics, the Perceived Value of Certification Tool, and questions regarding incentives offered by employers for certifica-tion. Survey responses were anonymous, and it took less than 10 minutes to complete. Descriptive statistics were used to analyze the results. Results: Results are pending. Conclusions: Pending.

Supported by: NoneDisclosure: Marijean Buhse, Heidi W. Maloni, Therese V. Burke, Elsie E. Gulick: Nothing to disclose. June Halper: Biogen Idec (fees for non-CME services from commercial interests or their agents).Keywords: Employment in MS, MS certified nurses

(CC20) ROLES AND RESPONSIBILITIES OF NURSE PRACTITIONERS AND PHYSICIAN ASSISTANTS IN MULTIPLE SCLEROSIS CAREMarijean Buhse,1 Heidi W. Maloni,2 Elsie E. Gulick,3 June Halper4

1School of Nursing, State University of New York at Stony Brook, Stony Brook, NY; 2Washington, DC VAMC, MS Center of Excellence, Washington, DC; 3Nursing, Rutgers, the State University of New Jersey, Ringoes, NJ; 4Consortium of Multiple Sclerosis Centers, Hackensack, NJ

Background: Delays in patient access to specialty physicians are driven by changing disease patterns and gaps between physician supply and demand. In order to meet the demand for care, many specialty practices have employed nurse practitioners (NPs) and/or physician assistants (PAs). With approximately 86,000 PAs and 140,000 NPs in practice in the United States, it is not known how many are in specialty areas or the roles they have in the practice. In one survey, 13.3% of NPs reported that they were in internal medicine specialty practices. Studies predict a growing demand for specialty nonphysician clinicians as the population ages. Many multiple sclerosis (MS) centers/specialty practices have integrated NPs and PAs into their practices. The roles differ widely between practices, and NPs and PAs in these practices have varying responsi-bilities. There has been no description of the roles and responsibilities undertaken by nonclinicians in MS care. Objectives: The objective of this study was to describe the roles and responsibilities of NPs and PAs in MS care. Methods: Using the IOMSN Google Forum, a survey was sent to all MS nurses who subscribe to the forum. If they were an NP, they were asked to complete the survey. All others were asked to forward the survey to any NP or PA who cared for patients with MS. The PAs have an informal e-mail network, and the survey was sent to one PA who distributed it through the network. The sur-vey consisted of demographics and a modified version of the Nurse Practitioner Satisfaction Survey (NPSS), a 28-item, 5-point, Likert-type survey instrument. Results: 64 NPs and PAs responded. Most non-physician clinicians were satisfied (43%) to very satisfied (46%) with their ability to give good patient care. A wide range in the numbers of patients seen daily was reported (2–20). Respondents indicated

(CC18) HOW WELL DO NEUROLOGY RESIDENTS RECOGNIZE MULTIPLE SCLEROSIS? ANALYSIS OF THE CLOSE THE LOOP RESIDENT CLINICAL ACUMEN ASSESSMENT PROJECTRachel Brandstadter,1 Christine Hannigan,1 Stephen Krieger2

1Neurology, Icahn School of Medicine at Mount Sinai, New York, NY; 2Icahn School of Medicine, Corinne Goldsmith Dickinson Center for Multiple Sclerosis, New York, NY

Background: Morning report is a universal component of neurol-ogy resident education and a crucial venue where future neurolo-gists’ clinical acumen is refined. Objectives: To characterize cases of demyelinating disease/multiple sclerosis (MS) seen by on-call neurology residents and to assess accuracy of their initial diagnostic impressions, identifying individual and systemic educational needs to improve MS diagnosis. Methods: For 3 academic years (July 2010 to June 2013), all patients independently assessed and presented by on-call junior residents during our daily morning report were data-based. We recorded the residents’ initial diagnostic impression and “closed the loop” by revisiting each case after reviewing the final diagnosis. We categorized cases as having a final diagnosis of a primary neurologic condition or as “non-neurologic” (medical, psy-chiatric, ophthalmologic, other). Neurologic cases were catalogued by etiology, including demyelinating disease/MS. We compared residents’ initial diagnostic impression to the final diagnosis to assess whether the initial impression was accurate or inaccurate. Results: 834 cases were presented in total, and 31 (3.7%) had a final diagnosis of demyelinating disease/MS. Overall resident diagnostic accuracy was 70.9%, with accuracy of 74.2% for demyelinating disease/MS. Residents’ highest accuracy was in ischemic stroke (82.3%) and seizure (75.6%), which were the most frequent diagno-ses presented (n = 121 and 59, respectively). MS-related errors were analyzed: there were 8 cases of demyelinating disease/MS that were initially missed, including those mistakenly diagnosed as central nervous system infection, medical illness, trauma, and neoplasm. Conversely, there were 13 cases erroneously initially diagnosed as demyelinating disease, which were ultimately determined to have other conditions including medical illness, neoplasm, neuropathy, and psychiatric illness. Conclusions: This project presents a novel educational initiative to assess and improve neurology residents’ clini-cal acumen. Diagnostic accuracy for identifying MS/demyelinating disorders was less than the accuracy of the most frequent diagnoses seen by residents (ischemic stroke and seizure), likely due to the smaller number of cases presented in this category. It is essential for future neurologists to be highly proficient in diagnosis of MS. By ana-lyzing the specific types of errors made, we can refine educational strategies to enhance residents’ MS-related diagnostic skills.

Supported by: NoneDisclosure: Rachel Brandstadter, Christine Hannigan: Nothing to disclose. Ste-phen Krieger: Acorda, Bayer HealthCare, Biogen Idec, EMD Serono, Genzyme, Questcor, Teva Neuroscience (consulting fees).Keywords: Comprehensive care and MS, Graduate medical education

(CC19) VALUE ADDED: MULTIPLE SCLEROSIS NURSE CERTIFICATION—REAL-WORLD IMPLICATIONSMarijean Buhse,1 Heidi W. Maloni,2 Therese V. Burke,3 Elsie E. Gulick,4 June Halper5

1School of Nursing, State University of New York at Stony Brook, Stony Brook, NY; 2Washington, DC VAMC, MS Center of Excellence, Washington, DC; 3MS Clinic, Institute for Immunology and Allergy Research, Sydney, Australia; 4Nursing, Rutgers, the State University of New Jersey, Ringoes, NJ; 5Consortium of Multiple Sclerosis Centers, Hackensack, NJ

Background: Certification for specialty nursing practice was devel-oped to recognize the specialized knowledge, skills, and experienc-es of nurses in a specialty area. This is demonstrated by achieving the standards identified by the nursing specialty and acknowledged by certification. The outcome of certification is to promote optimal health care for the population in the specialty area. Participation in certification is voluntary in most specialties, but it has been shown to be valued by nurses. In previous studies, certification is seen as

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(CC22) NMO IgG: THE IMPACT OF THE NMO BIOMARKER (NMO IgG) ON DIAGNOSIS AND TREATMENT OF NEUROMYELITIS OPTICA AND NEUROMYELITIS OPTICA SPECTRUM DISORDERLuis F. Tornes,1 Leticia Tornes,2 Melissa Ortega,2 Silvia Delgado,2 Janice Maldonado,2 William Sheremata,2 Kottil Rammohan2

1Florida International University, Miami, FL; 2Neurology, University of Miami, Miami, FL

Background: Neuromyelitis optica (NMO) is a severe central nervous system (CNS) demyelinating disease that preferentially affects the optic nerves and spinal cord. It was commonly diagnosed as multiple sclerosis (MS) in the past. Objectives: To character-ize demographics, natural history, diagnosis, and treatment effects on NMO and NMO spectrum disorder (NMOSD) patients in our clinic. Methods: The study was an IRB-approved retrospective chart review. Patients were identified with ICD-9 code of 341.0. Patients with either NMO or NMOSD were included, and all other diagnoses were excluded. Patient notes, laboratory results, and imaging find-ings were reviewed and collected. Results: A total of 130 patients were reviewed; of these, 94 were included. The vast majority were women (87%), with an average age of onset of 34.2. The patients were identified as non-Hispanic (63%) or Hispanic (37%) and white (47%), black (40%), other (7%), Asian (1%), or unknown (5%). The diagnostic lag was 5.2 years, with 11.2 years pre-2004 and 1 year post. Overall, 42% were initially diagnosed with MS; pre-2004 (69%) and post-2004 (28%). The initial presentation was transverse myelitis (TM) in 59%, optic neuritis (ON) in 31%, and both TM and ON in 10%. Pain was present in (80%). In those who presented with ON, 92.3% developed TM an average of 4.3 years later. In patients with TM presentation, 47% developed ON an average of 2.2 years later. Overall, 67% of patients were diagnosed with NMO and 33% with NMOSD. Most patients are currently on rituximab (75%), and in those who began therapy prior to their second episode (n = 31), 84% have not developed a second episode. Conclusions: The addition of the NMO biomarker has greatly reduced the diagnostic lag in NMO as well as prevented many who have started treatment after initial presentation from having a second event.

Supported by: NoneDisclosure: Luis F. Tornes, Leticia Tornes, Janice Maldonado: Nothing to dis-close. Melissa Ortega: National Multiple Sclerosis Society (grant/research support). Silvia Delgado: Bayer (consulting fees). William Sheremata: Bayer, Biogen (grant/research support); Novartis (consulting fees, grant/research support); Serono (con-sulting fees). Kottil Rammohan: Acorda, Biogen, Novartis, Teva (consulting fees, grant/research support); EMD Serono, GSK, National Institutes of Health (grant/research support); EMD Serono, Genentech, Pfizer, Questcor, Roche (consulting fees).Keywords: Immunology and MS

(CC23) WITHDRAWN

(CC24) AUDIT OF MULTIPLE SCLEROSIS PRACTICE AGAINST NICE GUIDELINES 2014Catherine B. Wingrove

Neurology, Sunderland Royal Hospital, Sunderland, United Kingdom

Background: Multiple sclerosis (MS) affects approximately 100,000 people in the United Kingdom. In 2014, the National Insti-tute for Health and Care Excellence (NICE) produced MS guidelines to replace the NICE clinical guideline (2003), covering diagnosis, information and support, treatment of relapse, and management of MS-related symptoms. After the NICE guideline of 2003, there was an audit of the Sunderland MS Service of time taken between initial referral to neurologic services and diagnosis. This audit measures the time between suspected MS and confirmed MS, and the time between a patient’s being deemed eligible for disease-modifying therapy (DMT) and receiving it. Objectives: To determine the time taken from an appointment with a neurologist to receiving a con-firmed diagnosis; and the time taken from when a patient becomes

that their duties beyond patient care included research, administra-tion, and patient education. Many spend their time teaching non-providers about MS, coordinating care between providers, working on insurance issues, and administering medication. The biggest challenges are time constraints and lack of administrative support. Conclusions: There are many nonphysician clinicians providing MS care, and most are satisfied with their role. Roles and responsibilities differ between practices. A larger study is planned to understand commonalities and differences in roles and patient satisfaction with these nonphysician clinicians.

Supported by: NoneDisclosure: Marijean Buhse, Heidi W. Maloni, Elsie E. Gulick: Nothing to disclose. June Halper: Biogen Idec (fees for non-CME services from commercial interests or their agents).Keywords: Employment in MS, Nonphysician clinicians

(CC21) PROVIDING SPECIALTY AND PRIMARY CARE TO UNDERSERVED MULTIPLE SCLEROSIS PATIENTS THROUGH A FEDERALLY QUALIFIED HEALTH CENTER (FQHC)Jessica D. Freeman,1 Michaela Welch,2 Alexandra Hempel,3 Michele Harrison,2 Thomas M. Stewart,2 Augusto A. Miravalle3

1Community HealthCorps, Metro Community Provider Network, Aurora, CO; 2Metro Community Provider Network, Aurora, CO; 3Department of Neurology, University of Colorado, Aurora, CO

Background: Federally qualified health centers (FQHCs) are generally well suited to meet the primary-care needs of underserved patients, including patients insured through Medicaid or Medicare, patients without insurance, and undocumented patients. In part, this is because FQHCs receive enhanced reimbursement from Medicaid and Medicare as well as other financial benefits. While well suited to meet the primary-care needs of the underserved, many FQHCs lack specialty-care services. For underserved patients with multiple sclerosis (MS), this may result in decreased access to specialty care. However, the laws governing FQHCs are flexible; therefore, spe-cialty care such as neurology may be added to an FQHC’s scope of services. To do this, an FQHC must submit a narrative to the Bureau of Primary Health Care indicating that the specialty care qualifies as “additional health services,” as defined by federal law. This is possible if the specialty care is “necessary for the adequate sup-port of the primary health services” and the target population needs the specialty. Objectives: To offer subspecialty and primary-care services to underserved patients with MS in a cost-effective manner through an FQHC. Methods: Working through a large FQHC (Metro Community Provider Network) and in collaboration with a variety of organizations, we obtained and expanded the scope of services to include MS specialty care. The MS clinic consists of an interdisciplinary team made up of a neurologist (from a nearby aca-demic MS specialty clinic, the Rocky Mountain MS Center), physician assistant, registered nurse, physical therapist, and care coordina-tor. The entire MS-specialized team is part time, but subspecialty clinicians are available by phone for urgent matters. Primary care is provided by full-time FQHC clinicians. Results: In the last year alone, approximately 150 patients, who would otherwise have had difficulty accessing MS experts, disease-modifying treatments, MRIs, or physical therapy services, were able to receive these and other services at reduced or no cost. The clinic serves as a medical home for our patients to ensure management of primary-care needs in an effort to reduce comorbidities. The MS clinic is funded, in part, by the Rocky Mountain MS Center and the National Multiple Sclerosis Society to provide additional services such as education classes and physical therapy. Conclusions: FQHCs may broaden their scope of practice to include subspecialty care. Further, patients who may not otherwise have access to specialty care can receive primary and coordinated specialized care in the same facility.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Comprehensive care and MS, Economic issues and MS

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Posters: Cognition and Psychosocial

Homebound Initiative Pilot Program ended on January 15, 2015. During supervision sessions, volunteers expressed that they enjoyed their monthly phone sessions with clients who cannot leave their homes. The chapter plans to expand the program and add three additional volunteers during the summer of 2015. Conclusions: Newly diagnosed people with MS, with and without mental health difficulties, benefit from additional emotional support, especially from individuals who know about the illness firsthand.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Psychological issues and MS

(CP08) ACUTE EFFECTS OF WALKING, CYCLING, AND YOGA EXERCISE ON COGNITION IN MULTIPLE SCLEROSISBrian M. Sandroff,1 Charles H. Hillman,1 Ralph H.B. Benedict,2 Robert W. Motl1

1Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL; 2Department of Neurology, University at Buffalo, Buffalo, NY

Background: Cognitive impairment is a highly prevalent, dis-abling, and poorly managed consequence of multiple sclerosis (MS). Exercise training represents a promising approach for managing cognitive impairment in this population. However, there is limited evidence supporting an optimal exercise stimulus for improving cog-nition in MS. Objectives: The current study compared the acute effects of moderate-intensity treadmill walking, moderate-intensity cycle ergometry, and guided yoga with quiet rest on executive con-trol in 24 individuals with relapsing-remitting MS without impaired cognitive processing speed using a within-subjects, repeated-mea-sures design. Methods: Participants completed four experimental conditions that consisted of 20 minutes of moderate-intensity tread-mill walking exercise, moderate-intensity cycle ergometer exercise, guided yoga, and quiet rest in a randomized, counterbalanced order. Participants underwent a modified-flanker task as a measure of executive control immediately prior to and following each condition. Results: Repeated-measures ANOVAs indicated general pre-to-post improvements in reaction time, but not accuracy, on the modified-flanker task for all three exercise modalities compared with quiet rest. However, there were additional, selective pre-to-post reductions in the cost of interfering stimuli on reaction time on the modified-flanker task for treadmill walking (F1,23 = 4.67, P = .04, ηp

2 =.17), but not cycle ergometry (F1,23 = 0.12, P = .73, ηp

2 < .01) or guided yoga (F1,23 = 0.73, P = .40, ηp

2 =.03), compared with quiet rest. Conclusions: The present results support treadmill walking as the modality of exer-cise that might exert the largest beneficial effects on executive control in people with relapsing-remitting MS without impaired cognitive pro-cessing speed. This represents an exciting starting point for delineat-ing the appropriate exercise stimulus (ie, modality and intensity) for inclusion in a subsequent longitudinal exercise training intervention for improving cognitive performance in this population.

Supported by: NoneDisclosure: Brian M. Sandroff, Charles H. Hillman: Nothing to disclose. Ralph H.B. Benedict: Acorda, Biogen, Novartis, Genzyme, Questcor (grant/research sup-port); EMD Serono (fees for non-CME services from commercial interests or their agents); Genentech, Sanofi, Biogen, Novartis (consulting fees). Robert W. Motl: Biogen, Acorda (consulting fees, grant/research support); EMD Serono (fees for non-CME services from commercial interests or their agents).Keywords: Exercise in MS, Psychological issues and MS

(CP09) AEROBIC FITNESS IS ASSOCIATED WITH INHIBITORY CONTROL IN PEOPLE WITH MULTIPLE SCLEROSISBrian M. Sandroff, Charles H. Hillman, Robert W. Motl

Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL

Background: There is a wealth of evidence examining the effects of aerobic fitness on executive control in the general population across the lifespan, but there is markedly less research on this topic in people with neurologic diseases such as multiple sclerosis (MS).

eligible for DMT therapy to receiving their chosen DMT treatment. Methods: A database of patients at Sunderland Hospital with a diagnosis of MS is kept. This retrospective study looked back at the records of these patients, including outpatient records, MRI records, and outpatient clinic letters. 25 patients who had made contact with the neurologic services from 6/9/09 to 1/22/14 had their notes analyzed to determine the time taken from an appointment with a neurologist in which MS was suspected to receiving a confirmed diagnosis; and the time taken from when a patient became eligible for DMT therapy to receiving their chosen DMT treatment. Results: Patients waited a median of 49 days between outpatient appoint-ment and diagnosis. The range was 0 to 381 days. This was com-pared to the 2003 audit, which had a median of 315 days with a range of 0 to 1764 days. Patients eligible for DMTs started treatment in a median time of 32 days. In this audit, one patient had a gap of 243 days while the patient considered whether to pursue treatment. In comparison, the Novo study in Spain found a median overall time from initial medical consultation to confirmation of the diagnosis by a specialized MS unit of 5.7 months and a median time from symptom onset to first treatment of 2 years. Conclusions: Sunderland Royal Hospital patients wait a comparably short time for their diagnosis and treatment, and the service has moved forward considerably since the last audit in 2003 and is favorable compared to previous audits.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Comprehensive care and MS

COGNITION AND PSYCHOSOCIAL

(CP07) THE IMPLEMENTATION OF EMOTIONAL SUPPORT PILOT PROGRAMS FOR INDIVIDUALS WITH MULTIPLE SCLEROSISEvan B. Marcus

Programs and Services Department, National Multiple Sclerosis Society, Greater Delaware Valley Chapter, Philadelphia, PA

Background: Research suggests that up to 50% of people with multiple sclerosis (MS) experience depression during their lifetimes. Emotional difficulties make dealing with an MS diagnosis even more challenging for patients with the disease. Thus, it is imperative that organizations working with this population provide innovative emotional support programming and services geared toward the pre-vention of the onset of depression as a secondary symptom of MS. Objectives: To develop new means for providing emotional sup-port to members of the National Multiple Sclerosis Society’s Greater Delaware Valley Chapter. Methods: Chapter staff created two pilot programs tailored to support clients with MS. The Peer Mentor Pilot Program focused on helping newly diagnosed members with one-on-one, in-person meetings with mentors who have lived with the illness for at least 3 years. Over the course of 3 months, five mentors were matched with five peers. Mentors provided emotional support and company that only someone who understands what it is like to have MS can give. This pilot program differs from other NMSS peer mentor programs in that peers met with mentors in person and in their communities. The chapter’s Homebound Initiative Pilot Program involved training nursing home residents with MS to provide emo-tional support by phone to socially isolated homebound clients in the community. Volunteers for both programs received training sessions regarding giving emotional support from chapter staff. These volun-teers also participated in monthly supervision sessions. Homebound Initiative volunteers were expected to spend 1 hour per month on the phone with homebound individuals. Results: Mentor and peer participants in the Peer Mentor Pilot Program overwhelmingly felt they benefited from the program. The chapter has approved an ongoing Peer Mentor Program for the 2014–2015 fiscal year. The

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of the Cleveland Clinic Foundation in Cleveland, Ohio, between 1/01/2010 and 12/18/2014. Although IRB approval has been received and data have been acquired, data analyses are not yet complete. Planned data analyses involve using time-to-event survival analysis, looking at the time since first neurology appointment at the Mellen Center until first BM appointment as primary outcome of interest. Kaplan-Meier curves will be used to illustrate patterns in time until BM appointment. Results: In process. Conclusions: In process.

Supported by: NoneDisclosure: Ben Greenberg: Consortium of Multiple Sclerosis Centers (grant/research support). Amy Sullivan: Consortium of Multiple Sclerosis Centers, National Multiple Sclerosis Society (grant/research support). Lucille J. Carriere, Youran Fan: Nothing to disclose.Keywords: Comprehensive care and MS, Psychological issues and MS

(CP11) BEHAVIORAL MEDICINE IN MULTIPLE SCLEROSIS: EXPLORING CHANGES IN EMOTIONAL AND PHYSICAL FUNCTIONINGAmy Sullivan,1 Ben Greenberg,2 Lucille J. Carriere,1 Youran Fan3

1The Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH; 2Psychiatry and Psychology, Cleveland Clinic Foundation, Cleveland, OH; 3Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, OH

Background: Multiple sclerosis (MS) is a disease in which approxi-mately 50% of individuals will experience depression and 40% anxiety at some point during their disease, which is four times as high as in any other neurologic condition. The completed suicide rate is 7.5 times as high as in the general population. In addition, anxiety is reported more often than depression in neurology clinics and has been linked to the presence of exacerbations and pseu-doexacerbations; if left untreated, it can worsen MS symptoms by increasing functional impairment, decrease adherence to treatment, worsen quality of life, and lead to suicidal ideation and suicide completion. Mind-body interventions such as exercise, relaxation, stress management, and cognitive-behavioral therapy have been helpful in managing these symptoms and in the prevention of brain lesions. This has highlighted the benefits of psychotherapy after treat-ment; however, there has been no report of change in emotional and physical functioning over time in MS patients who chose to receive health psychology services versus those who did not. In addition, no study has examined whether the disease course has any significance in the outcome of behavioral medicine interventions. Objectives: 1) identify how emotional and physical functioning changes over time in patients who choose to receive health psychology (HP) services at the Mellen Center versus those who do not, and 2) determine whether the MS disease course has any significant impact on the outcomes. Methods: Data were retrospectively collected for 8235 patients with MS seen at the Mellen Center at the main campus of the Cleve-land Clinic between 1/01/2010 and 12/18/2014 using an IRB-approved database. Patients 18 years old or older with a diagnosis of MS will be included in the sample. Data that will be used for this study will be exported from the Knowledge Program database for all patient visits, which includes inventories on mood, health status, and quality of life. Because patient follow-up is variable depending on symptom severity, the data will be grouped by visit number. At each visit number, averages for the sample will be reported for all inven-tories. Two primary analyses will be conducted to evaluate whether patients who receive HP benefit from treatment. First, change scores will be calculated for patients who receive HP from emotional and physical functioning at intake versus three sessions into treatment. Paired t tests will be used to determine whether this brief period of intervention results in patient improvement. Second, multilevel mod-eling will be used for the full sample of 8235 patients, examining changes in physical and emotional functioning since time of diagno-sis based on course of MS, demographic factors, and receipt of HP. Results: In process. Conclusions: In process.

Accordingly, it is unknown if the well-established pattern of associa-tions between higher aerobic fitness and better inhibitory control in the general population exists among people with MS. Objectives: The current cross-sectional study examined the effects of aerobic fit-ness on inhibitory control measures, using a modified flanker task, in 28 people with MS and 28 healthy controls matched by age, sex, body-mass index, and education. Methods: All participants underwent administration of the modified flanker task in a quiet, sound-dampened room, followed by an incremental exercise test to exhaustion on a cycle ergometer with expired gases analyzed using indirect calorimetry for measurement of aerobic fitness as peak oxy-gen consumption (VO2peak). Results: People with MS demonstrated lower VO2peak and slower, less accurate performance on the modified flanker task compared with matched controls. VO2peak was similarly associated with measures of inhibitory control (ie, reaction time) in the MS sample and the matched control sample. VO2peak, but not group (ie, MS versus control), predicted reaction time on both con-gruent and incongruent trials of the modified flanker task, irrespective of age, sex, and education. Conclusions: The current results pro-vide support for the development of aerobic exercise training inter-ventions for improving inhibitory control in people with MS, much like what has been successfully undertaken in the general population.

Supported by: NoneDisclosure: Brian M. Sandroff, Charles H. Hillman: Nothing to disclose. Robert W. Motl: Biogen, Acorda (consulting fees, grant/research support); EMD Serono (fees for non-CME services from commercial interests or their agents).Keywords: Exercise in MS, Psychological issues and MS

(CP10) BEHAVIORAL MEDICINE IN MULTIPLE SCLEROSIS: WHAT DETERMINES WHO RECEIVES SERVICES?Ben Greenberg,1 Amy Sullivan,2 Lucille J. Carriere,2 Youran Fan3

1Psychiatry and Psychology, Cleveland Clinic Foundation, Cleveland, OH; 2The Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH; 3Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, OH

Background: A recent literature review found strong evidence that stress was linked with the onset of multiple sclerosis (MS) or relapse of symptoms (Artemiadis, Anagnostouli & Alexopoulos, 2011). Cog-nitive, emotional, and behavioral reactions to diagnosis and disease progression were also predictive of illness-related functional impair-ment (Dennison et al., 2010). Furthermore, there is evidence that for patients with MS, emotional distress, such as depression or anxiety, fatigue, and quality of life are all reciprocally related with disease progression (Pittion-Vouyovitch et al., 2006). The disease progres-sion of MS was also associated with other physiological changes including autonomic dysfunction (Flachenecker et al., 2001). How-ever, several mind-body interventions such as exercise, cognitive-behavioral therapy, relaxation, and stress management were benefi-cial for patients with relapsing-remitting MS (RRMS) to improve stress, locus of control, and emotional distress (Artemiadis et al., 2012), quality of life (Sung et al., 2013), fatigue (van Kessel et al., 2008), and the occurrence of new brain lesions (Mohr, 2012). Since 2010, over 8000 patients with MS have been treated at the Mellen Center for Multiple Sclerosis at the main campus of the Cleveland Clinic. Hundreds of these patients have been referred to receive services from behavioral medicine (BM) for issues including emotional distress such as depression or anxiety; improving coping skills; adjustment to, and acceptance of, diagnosis with MS; and increasing quality of life. Despite the large number of patients with MS who are seen, the decision of which patients are referred to receive services remains unclear. Patient-specific characteristics (eg, age, disease course, race, insurance, previous psychiatric diagnosis) and referring provid-er characteristics may both play a role in determining which patients are referred to receive services and could be evaluated to optimize the referral process. Objectives: To evaluate factors that contribute to the amount of time passed until patients are seen by BM. Meth-ods: Data were retrospectively gathered for 8235 patients with MS seen at the Mellen Center for Multiple Sclerosis at the main campus

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investigate whether patients identifying problems with pain, depres-sion, or anxiety during screening, when given the opportunity to identify multiple problems, were also more likely to endorse concerns with cognitive functioning. Methods: In support of medical care, 259 patients at a southeastern US MS center were screened (79.5% female, 55% white, mean age 46.67 years) for various psychosocial problems under the purview of health psychology. Results: Using logistic regression, patients who endorsed being bothered by pain were nearly four times as likely to report coexistence of subjective concern about cognitive functioning (P = .022) as those who did not. Patients who identified depression as a current problem were more than three times as likely to also report cognitive concerns (P = .005) as those without reported concern of depression. There was a nonsignificant trend for patients who identified experiencing anxiety to be more than twice as likely to report cognitive concerns as well (P = .074) compared to those who did not report anxiety. Conclu-sions: These results support that patients’ subjective complaints of pain, depression, and anxiety often co-occur with concerns about cognitive functioning at the time of screening. Results highlight the importance of clinicians providing patients with opportunity to iden-tify multiple concerns before selecting the focus of intervention. Facili-tating, through screening, patients’ self-reporting of pain, depression, and anxiety as areas of concern when reporting cognitive concerns may strengthen the provider’s ability to educate patients on treatment interventions that impact pain, depression, and anxiety (and often, as a consequence, cognitive functioning).


(CP14) COGNITIVE EVOLUTION IN TYSABRI-TREATED MULTIPLE SCLEROSIS PATIENTSFrancois H. Jacques,1 Brian T. Harel,2 Adrian J. Schembri,3 Chantal Paquette,1 Brigitte Bilodeau,1 Pawel Kalinowski3

1Clinique Neuro-Outaouais, Gatineau, QC, Canada; 2Cogstate, New Haven, CT; 3Cogstate, Melbourne, Australia

Background: Cognitive dysfunction affects up to 65% of multiple sclerosis (MS) patients and progresses over time. Natalizumab has been shown to be superior to placebo in preserving cognitive func-tion for the first 2 years of therapy. Objectives: The objectives of this study are to understand the impact of natalizumab on cognition beyond 2 years of therapy and to investigate whether baseline char-acteristics are predictive of clinical response. Methods: This is a single-center, 24-month, observational study. Sixty-three patients treat-ed with natalizumab were assessed prior to monthly infusions using a Cogstate battery and the Symbol Digit Modalities Test (SDMT). A Beck Depression Inventory (BDI) was administered every 4 months. Patient demographics, including EDSS, MSSS, education level, age, MS disease duration, BDI scores, natalizumab treatment duration, and presence of cognitive impairment, were collected at baseline. A linear mixed model was conducted with duration of natalizumab therapy as a between-subjects factor (≤2 or >2 years), assessment as a within-subjects factor, and MSSS as a covariate. All patients in the ≤2 years group were treated with natalizumab for less than 2 years prior to baseline. All patients in the >2 years group were treated with natalizumab for at least 2 years prior to baseline (mean 3.6 years). Results: There were no statistically significant differences between the key demographic variables aside for the MSSS (P = .0074). No patient showed evidence of sustained cognitive deterioration over the 24-month period. Irrespective of time on natalizumab, significant improvements were observed at the group level in executive func-tion, verbal memory, and working memory, whereas processing speed and attention remained unchanged. Impaired cognition or any other baseline parameter did not influence the trajectory of cognitive change over 24 months. Conclusions: Our results suggest that natalizumab preserves cognitive function, including the ability to learn, for 4 years and beyond of continuous therapy. This occurs irrespective of baseline characteristics.

Supported by: NoneDisclosure: Amy Sullivan: Consortium of Multiple Sclerosis Centers, National Multiple Sclerosis Society (grant/research support). Ben Greenberg: Consortium of Multiple Sclerosis Centers (grant/research support). Lucille J. Carriere, Youran Fan: Nothing to disclose.Keywords: Complementary/alternative therapies in MS, Comprehensive care and MS, Psychological issues and MS

(CP12) ASSESSMENT OF PERSONALITY TRAITS, MEMORY, AND VISUAL ATTENTION IN PEOPLE WITH MULTIPLE SCLEROSISAna M. Canzonieri, Mauricio O. Bando Sr., Lucas F Santos Sr., Jean I. Francisco, Taislandia Silva, Andira A. Ribeiro, Fernanda M. Marques, Liliana Russo, and Maria C. Giacomo

Research, ABEM–Brazilian Multiple Sclerosis Association, São Paulo, Brazil

Background: Multiple sclerosis (MS) is a chronic disease affect-ing the central nervous system that alters the transmission of nerve impulses, causing emotional changes, cognitive impairment, and psy-chiatric disorders, depending on the affected region. Objectives: To assess sociodemographic traits, memory type characteristics, and visual attention in people with MS. Methods: Application of the neuropsychological tests Selective Attention Visual Scale (EAVS) and Faces of Visual Memory (MVR) and the psychological test Color Pyramid of Pfister (TPC), which consists of the construction of three pyramids with colored cards on a mold. The sample consisted of 19 women and 7 men aged 26 to 68 years (mean 45.3, SD 12.6); 50.0% were married, 65.4% had higher education (complete and incomplete), 77.0% had a duration of diagnosis of over 5 years, 80.8% had the relapsing-remitting (RR) type of MS, and 46.1% had an Expanded Disability Status Scale (EDSS) score of 2.5. Results: In EAVS and MVR, 84.7% displayed average scores. In TPC, 88.5% of people had orderly execution, indicating rigidity; 57.7% performed the action in ascending order, showing more strength; 53.8% had wide reception of stimuli, indicating greater openness; 53.8% showed a formal aspect of the construction, with a predominance of carpet in the three pyramids. A statistically significant correlation was found between age group and gender (P = .010), with a prevalence in females over 51 years; between age group and EDSS score (P = .024), with a predominance of EDSS score up to 2.5 in the group aged 25 to 40; and between EDSS and EM (P = .007), with the prevalence of EDSS 2.5 for the RR group. The finding of the formal aspect (P = .011), which was predominantly in the construction of carpet pyramids, indicates cognitive deficits. Conclusions: The characteristics of memory type and visual attention are in the median range. Personality traits demonstrate rigidity. Younger people have an EDSS up to 2.5, the prevalent type of MS is RR, and there is a prevalence of women in the age group over 51 years.

Disclosure: Nothing to discloseKeywords: Complementary/alternative therapies in MS, Comprehensive care and MS, Psychological issues and MS

(CP13) THE VALUE OF CLINICAL SCREENINGS FOR CONCURRENT PROBLEMS IN PATIENTS WITH MULTIPLE SCLEROSIS WHO IDENTIFY AS HAVING COGNITIVE PROBLEMSRebecca M. Floyd, Kimberly Lewis, Eliot Lopez, Thomas Toomey, Kena Arnold, Lara Stepleman

Georgia Regents University, Augusta, GA

Background: Research indicates that as many as 65% of patients with multiple sclerosis (MS) will exhibit cognitive impairment. Pain, depression, and anxiety are known factors that adversely affect cognitive functioning, but these influences are often unrecognized by patients. If patients communicated coexistence of these issues at the time they reported cognitive concerns, opportunities for educa-tion on the role of psychosocial factors in cognitive dysfunction could increase the likelihood that patients would consider rather than discount the benefits of psychosocial treatment interventions for enhancing cognitive functioning. Objectives: This study aims to

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tools provide scores for individual cognitive domains. Objectives: To explore the predictability and effect size between the SDMT and NeuroTrax computerized cognitive testing (NT-CCT) domains in people with MS who self-report employment status. Methods: Ret-rospective review of people with MS referred for screening cognitive testing in the course of routine clinical care evaluated with both the oral version of the SDMT and NT-CCT on the same day. Results: There were 113 MS patients with a mean age of 48.9 ± 11.3 years; 85% were female. The standardized SDMT score (Centofani, 1975 age norms) significantly (P < .001) correlated with NT-CCT Global Cognitive Score (GCS; r = 0.64), and executive function (r = 0.60). The SDMT and NeuroTrax GCS predict employment status (P < .001). The effect size (Cohen’s d) of the NT-CCT GCS was 0.83, and of the SDMT was 0.70. That of the NT-CCT Executive Function index was 0.87. In the NeuroTrax Catch Game (scores standardized for age and education), overall score predicted employment (P < .001, d = 0.92). Unemployed people with MS had NT-CCT cognitive domain index scores >1SD below average for cognitively healthy age and education norms: 0 index scores (>1SD below), 34% unemployed; 2 index scores, 69%; 3 or more index scores, 75% (P < .001, d = 0.72). Conclusions: Unemployed MS patients dem-onstrated reduced cognitive function relative to employed patients. SDMT and NT-CCT screening both significantly differentiate people with MS who are employed from those who are not. NT-CCT predict-ability of employment provides a greater effect size for this differen-tiation. NT-CCT provides an easy, independent, objective screening tool highly predictive of employment status in people with MS. Objec-tive assessment of cognitive function is an important adjunct to EDSS in routine MS care.

Supported by: NoneDisclosure: Mark Gudesblatt, Myassar Zarif, Barbara Bumstead, Marijean Buhse, Lori Fafard, Daniel Golan, Cynthia Sullivan, Jeffrey Wilken: Nothing to disclose. Glen Doniger: NeuroTrax Corp (salary).Keywords: Comprehensive care and MS, Economic issues and MS, Employment in MS

(CP17) DIFFERENCES IN FUNCTIONING: WHO GETS REFERRED TO HEALTH PSYCHOLOGY?Lucille J. Carriere,1 Ben Greenberg,2 Amy Sullivan,1 Youran Fan3

1The Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH; 2Psychiatry and Psychology, Cleveland Clinic Foundation, Cleveland, OH; 3Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, OH

Background: Neurologists are increasingly being called to address mental health issues with multiple sclerosis (MS) patients. However, evidence suggests a discrepancy between the high rate of mood symptoms in the MS population and lack of adequate mental health services. The complexity in distinguishing mood and MS symptoms is difficult and often contributes to the disparity. Disease severity and time since diagnosis have been found to be strongly correlated with mood symptoms in MS patients. However, if demo-graphic characteristics and disease-specific variables are controlled for, it is unclear whether patients with MS who are referred for health psychology (HP) differ from those who are not in terms of emotional and physical functioning. That is, do patients receiving a referral to HP have increased emotional distress, decreased quality of life, and worsened physical functioning at time of referral compared to patients who do not despite having equivalent demographic and disease-related characteristics? Objectives: To examine the baseline differences in psychological (PHQ9, GAD7, and EQ5D) and physi-cal (25-Foot Timed Walk, Nine-Hole Peg Test) functioning between patients with MS who receive HP services and those who do not after controlling for demographic information, disease course, and length of time since disease onset. Methods: This is a retrospective, observational, IRB-approved study. Study population: adult patients (age 18 and up) receiving MS treatment from the Mellen Center for MS Treatment and Research during a 4-year period (N = 8235). Planned analyses include generating propensity scores for patients

Supported by: Biogen IdecDisclosure: Francois H. Jacques: Biogen Idec, Genzyme, Roche (infusion clinic); Biogen Idec, Sanofi, Novartis, Genzyme, Merck Serono, Roche, GSK (consulting fees, grant/research support). Brian T. Harel: Cogstate (salary). Adrian J. Schem-bri, Chantal Paquette, Brigitte Bilodeau, Pawel Kalinowski: Nothing to disclose.Keywords: Cognition, Disease-modifying treatments in MS

(CP15) PILOT STUDY SUGGESTS LINK BETWEEN LOW VITAMIN D AND EXECUTIVE FUNCTION IN MULTIPLE SCLEROSISGabriel Hoffnung,1 Roseann Archetti,1 Lisa Glukhovsky,1 Mary Ann Picone,2 Clover E. Youn,3 Frederick W. Foley2

1Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY; 2Holy Name Medical Center, Teaneck, NJ; 3Touro College of Osteopathic Medicine, New York, NY

Background: Vitamin D has become increasingly relevant within the multiple sclerosis (MS) literature in recent years, as low levels of vitamin D have been shown to predict MS relapses and correlate with overall disease worsening. Cognitive impairment is a common and debilitating MS symptom as well as an important indicator of general disease state. It is not known whether a relationship exists between vitamin D deficiency and MS cognitive impairment. Objec-tives: To test pilot data for a possible relationship between MS cognitive impairment and vitamin D deficiency in advance of a larger prospective study. Methods: Analysis was performed on a subset (n = 22) of MS patients from a large database that is part of an ongo-ing study of MS cognitive function at the Comprehensive MS Center at Holy Name Medical Center in Teaneck, NJ. All patients were given a battery of neurocognitive tests (MACFIMS battery), and data were analyzed for those patients with available vitamin D levels mea-sured within 6 months of cognitive testing. Cognitive impairment was measured both as an overall score and according to discrete func-tional domains. Spearman rank order correlations (rho) were run to measure correlation. Results: There were no significant correlations observed between vitamin D deficiency and general cognitive impair-ment or discrete domains. The strongest correlation observed was that between vitamin D and executive function (rho = 0.369), which trended toward significance (P = .11) even in this small sample. Conclusions: The sample analyzed was too small to determine any relationship between vitamin D deficiency and MS cognitive impair-ment; however, data suggest that when conducting a more complete study, attention should be given to discrete domains of cognitive func-tion and particularly to executive functions.

Supported by: NoneDisclosure: Gabriel Hoffnung, Roseann Archetti, Lisa Glukhovsky, Mary Ann Picone, Clover E. Youn: Nothing to disclose. Frederick W. Foley: Bayer (consult-ing fees).Keywords: Cognitive impairment and MS, Psychological issues and MS

(CP16) MULTIPLE SCLEROSIS, EMPLOYMENT, COGNITIVE PROFILE, AND COGNITIVE TESTING: PREDICTABILITY OF SDMT AND COMPUTERIZED COGNITIVE TESTINGMark Gudesblatt,1 Myassar Zarif,1 Barbara Bumstead,1 Marijean Buhse,2 Lori Fafard,1 Daniel Golan,3,4 Cynthia Sullivan,2 Jeffrey Wilken,2 Glen Doniger5

1South Shore Neurologic Associates, Patchogue, NY; 2School of Nursing, State University of New York at Stony Brook, Stony Brook, NY; 3Department of Neurology, Carmel Medical Center, Haifa, Israel; 4Rapparport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; 5NeuroTrax Corporation, Modiin, Israel.

Background: Cognitive impairment is common in people with MS (MS). Routine cognitive screening in MS care is not common. Unemployment is common in people with MS. Employment status may be affected by cognitive impairment, not apparent by EDSS. MS affects cognition domains differently in people with MS. Easily avail-able and utilized objective cognitive screens are needed to evaluate cognition in MS independent of EDSS or MRI. The Symbol Digit Modalities Test (SDMT) is not commonly used in routine MS care. As a single score cognitive measure, the SDMT does not provide infor-mation about individual cognitive domains or the presence/degree of impairment in multiple domains. Computerized cognitive screening

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1Rehabilitation Medicine, University of Washington, Seattle, WA; 2VA Puget Sound HCS, Seattle, WA; 3Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA

Background: Fatigue and depression are common and often per-sistent symptoms for individuals with multiple sclerosis (MS). There is considerable need for easily implemented and broadly appli-cable psychosocial treatments that address these issues. Objectives: To evaluate the impact of a physical activity intervention consisting of telephone counseling with home-based monitoring to improve fatigue and depression in individuals with MS. Methods: Randomized controlled trial. Sixty-four veterans with MS received either telephone counseling (TC; n = 31), or self-directed physical activity education (EC; n = 33). TC included mailed graphic feedback, six telephone counseling sessions using principles of motivational interviewing, and telehealth home monitoring to track progress on exercise goals. Booster sessions were provided when indicated. EC consisted of advice to exercise and a DVD with examples of in-home exer-cises for multiple physical ability levels. Assessment was conducted at baseline and at 3-month and 6-month follow-up. Results: TC par-ticipants reported significantly increased physical activity (d = 0.98), reduced fatigue (d = −0.37), and reduced depression (d = −0.50) relative to EC participants. 33.3% of individuals receiving TC experi-enced clinically significant improvement in fatigue, and 53.3% expe-rienced clinically significant improvement in depression. Improve-ments in physical activity partially mediated improvements in fatigue with a similar trend for depression. TC was highly feasible (par-ticipants completed 99.5% of scheduled telephone sessions) and well tolerated (100% rated it highly successful). Conclusions: Telephone-based counseling with home monitoring is a promising modality to improve physical activity and treat fatigue and depression.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Complementary/alternative therapies in MS, Comprehensive care and MS, Psychological issues and MS

(CP20) SUPPORT NETWORK FOR YOUNG ADULTS WITH MULTIPLE SCLEROSISSara Schaefer

Linda Morgante MS Care Center, Maimonides Medical Center, Brooklyn, NY

Background: Multiple sclerosis (MS) is the most prevalent neuro-logic disease affecting young adults. MS patients not only experience physical symptoms, but may also experience psychological problems. These include, but are not limited to, depression and anxiety. The rates of emotional disorders are significantly higher in MS patients than in the general population (Minden, Turner, Kalb & Burke, 2014). Support groups are understood to improve psychological well-being (Wakefield, Bickley & Sani, 2013), and our MS care cen-ter has a support group that is open to patients of all ages. Younger patients expressed interest in attending a support group; however, when invited to attend our established group, some patients were uncomfortable interacting with patients living with advanced MS for fear of long-term disease progression within themselves. Objec-tives: Facilitate a meaningful support network for young adults with MS and their unique needs. Methods: An advanced practice nurse facilitates the support network, consisting of monthly 2-hour support group meetings and e-mail support. Topics of discussion center on how MS affects a patient’s life, including cognition, fatigue, nutrition, complementary and alternative medicines, current research, and positive psychology. The facilitator consults with nutrition specialists and cognition experts and has National Multiple Sclerosis Society information packets available. Patients receive flyers for upcoming meetings by email and are encouraged to respond with comments or questions regarding the topic. Participant ownership is encouraged through the selection of topics, meeting times, and open discourse. Results: Patients report satisfaction in finding others with similar issues and symptoms. They appreciate the ability to freely discuss concerns, symptoms, and emotions. The group members are able to voice frustrations and feelings more freely than when visiting with the

receiving HP to control for demographic information, disease course, and length of time since disease onset. Following propensity score matching between patients who did or did not receive HP, general estimating equations will be used to evaluate the differences on psy-chological and physical outcomes. Results: Ongoing. Conclu-sions: Ongoing.

Supported by: NoneDisclosure: Lucille J. Carriere, Youran Fan: Nothing to disclose. Ben Greenberg: Consortium of Multiple Sclerosis Centers (grant/research support). Amy Sullivan: Consortium of Multiple Sclerosis Centers, National Multiple Sclerosis Society (grant/research support).Keywords: Comprehensive care and MS, Health psychology, Psychological issues and MS

(CP18) MULTIPLE SCLEROSIS CARE AND TRANSGENDERED PEOPLE: A CASE STUDYLucille J. Carriere, Mary R. Rensel, Amy Sullivan

The Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH

Background: Recent nationwide surveys have highlighted the sig-nificant disparities in health care for transgendered individuals, often referred to as a “priority population.” The gaps in quality health care are often attributed to internalized stigma from providers or lack of training in medical school/residency training programs in addressing transgender-specific health-care needs. With regard to multiple scle-rosis (MS) in transgendered people, there is a significant dearth of best practice guidelines within the literature for health-care providers. Specifically, there is little empirical evidence regarding the intersec-tion between cross-sex hormone replacement therapy (HRT), neuro-immunologic processes, and disease-modifying treatments (DMTs). Best practice guidelines are also lacking for culturally sensitive communication between patients and providers (preferred names, pronouns, etc.) and coordination between medical and nonmedical providers (health psychology, social work, and endocrinology) to facilitate high-quality MS care for such an underserved population. A case study is presented of an 18-year-old MS patient identifying as a female at initial contact and later as a transgendered male (female-to-male) receiving neurologic/medical care at a comprehensive care center (CCC) for MS. A thorough medical history will be discussed, highlighting presenting/current neurologic symptoms, neurologic test-ing, imaging data, DMTs, and MS disease course. Additionally, the role of health psychology services in the patient’s care at the CCC will be addressed, including psychosocial history, psychological assessments, and the course of psychotherapy. Emphasis will also be placed on discussing the intersection between gender identity issues, mood symptoms, and MS-related symptoms. Following discussion of the case study, the authors will present best practice guidelines for multidisciplinary providers in a CCC for MS in serving a trans-gendered population. Recommendations will be based on adapted practice guidelines from the gay and lesbian health-care literature, and reflections from the case study. Guidelines will be applicable to all providers in MS centers and address the following issues: cultur-ally sensitive communication between patients and providers, use of cross-sex HRT, utilization of health psychologists in coordinating care, advocacy efforts, and collaboration with other non-CCC providers.

Supported by: NoneDisclosure: Lucille J. Carriere: Nothing to disclose. Mary R. Rensel: Biogen, Genzyme, Novartis (consulting fees). Amy Sullivan: Consortium of Multiple Scle-rosis Centers, National Multiple Sclerosis Society (grant/research support).Keywords: Comprehensive care and MS, Psychological issues and MS, Sexuality/gender issues in MS

(CP19) IMPROVING FATIGUE AND DEPRESSION IN INDIVIDUALS WITH MULTIPLE SCLEROSIS USING TELEPHONE-ADMINISTERED PHYSICAL ACTIVITY COUNSELINGAaron P. Turner,1 Narineh Hartoonian,2 Alicia Sloan,2 Marisa Benich,2 Daniel Kivlahan,3 Christina Hughes,2 Abbey Hughes,1 Jodie K. Haselkorn1

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way, healthy family function is crucial to MS patients, but, ironically, MS itself places a great strain on families. It is difficult to measure the effect of MS on patients’ families, and little is known about this important relationship. Objectives: To measure both patient and family assessment of family function and consider the possible dif-ferences in perception and the role of this perception in patient self-efficacy. Methods: 79 patients with confirmed MS were given measures of disease severity and self-esteem (the Multiple Sclerosis Self-Efficacy Scale; MSSE), while both patients and their family mem-bers completed the McMaster Family Assessment Device (FAD) as a measure of perceived family function. Pearson r correlations were run to determine the relationship of patient perception and family perception in assessing family function as well as the effects of both of these perceptions on patient perceived self-efficacy. Results: The cohorts of MS patients and MS family members showed no signifi-cant difference in perceived family function; patient mean = 1.916, family mean = 1.922 (on a scale of 1–4 with lower scores implying better function). However, in comparing the ratings of individual MS patients with ratings of their own family members, scores of family members differed from those of patients by a mean of 0.40 (SD in this population is 0.58). Patient and family perceptions of family func-tion were significantly, but only moderately, correlated (r = 0.54, P < .001). In predicting patient self-efficacy, the patient’s perception of family function was significant (r = −0.354, P = .002), while the fam-ily member’s perception of functioning was only trending toward sig-nificance as a predictor of patient self-efficacy (r = −0.202, P = .08). Conclusions: Moderate discrepancy between patient perception of family function and family perception is likely. Of the two, it is patient perception that is more likely to correlate with poorer self-efficacy outcomes. Thus, when considering the role of family and disease burden in MS, it is important to distinguish between the experience and perception of patients and that of their families. It is important for health-care providers to be aware of the effects of MS on families, for the benefit of both MS patients and their families.

Supported by: NoneDisclosure: Gabriel Hoffnung, Judith B. Levin, Lisa Glukhovsky, Jason Botv-inick, Vance Zemon: Nothing to disclose. Frederick W. Foley: Bayer (consulting fees).Keywords: Comprehensive care and MS, MS and the caregiver/family, Psycho-logical issues and MS

(CP23) THE EFFECTS OF FAMILY FUNCTION AND DISABILITY ON PERCEIVED SELF-EFFICACY IN MULTIPLE SCLEROSIS: SELF-EFFICACY FUNCTION AND SELF-EFFICACY CONTROLGabriel Hoffnung,1 Judith B. Levin,2 Lisa Glukhovsky,1 Jason Botvinick,1 Vance Zemon,1 Frederick W. Foley3

1Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY; 2Levindale Hebrew Geriatric Center and Hospital, Baltimore, MD; 3Holy Name Medical Center, Teaneck, NJ

Background: Self-efficacy has been shown to be a strong predic-tor of both psychological and general well-being. Multiple sclerosis (MS) and its accompanying disability can strongly affect a patient’s feelings of self-efficacy. The construct of self-efficacy is a composite of a number of beliefs and emotions relating to self-perception, and there are a number of ways in which an illness such as MS can affect self-perception. One distinction is that between self-efficacy function, the belief in one’s ability to take care of daily needs, and self-efficacy control, the extent to which a patient feels in control of his or her life. It appears that MS differentially effects self-efficacy function more than self-efficacy control, but the mechanisms for this differential effect are unknown. Objectives: Compare the scores of MS patients on items of self-efficacy function and self-efficacy control and examine whether the factors of disability and family function may differen-tially affect the two scales. Methods: 79 patients with confirmed MS were given measures of disease severity and self-esteem (the Multiple Sclerosis Self-Efficacy Scale; MSSE) as well as a measure of MS disability. Both patients and their family members completed

doctor or nurse in routine follow-up visits. Group members state they look forward to monthly meetings. Conclusions: The addition of a young-adult support network is a critical factor in promoting well-ness in the comprehensive care of MS patients. The continuation of monthly peer support-group meetings will help improve psychologi-cal well-being of the participants. When patients identify with others experiencing similar disease progression, it will enhance strategies to balance their MS symptoms, work, stress, school, and family issues.

Disclosure: Biogen Idec (consulting fees)Keywords: Comprehensive care and MS, Management of activities of daily living in MS, Nursing management in MS

(CP21) THE EFFECTS OF FAMILY FUNCTIONING ON PATIENT SELF-EFFICACY IN MULTIPLE SCLEROSISJudith B. Levin,1 Gabriel Hoffnung,2 Lisa Glukhovsky,2 Jason Botvinick,2 Vance Zemon,2 Frederick W. Foley3

1Levindale Hebrew Geriatric Center and Hospital, Baltimore, MD; 2Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY; 3Holy Name Medical Center, Teaneck, NJ

Background: Perceived self-efficacy has been shown to be a strong predictor of both psychological and general well-being. It is understood that chronic disabling illness such as multiple sclerosis (MS) may affect a patient’s feelings of self-efficacy. It is also under-stood that family and social support play a crucial role in healthy self-efficacy, especially in individuals with considerable disease burden. Little is known regarding the relationship of family func-tion and self-efficacy in MS. Objectives: To evaluate the effects of family function on the MS patient’s perceived self-efficacy while controlling for disease severity and disability. Methods: 79 patients with confirmed MS were given measures of disease severity and self-efficacy (the Multiple Sclerosis Self-Efficacy Scale; MSSE), while both patients and their family members completed the McMaster Family Assessment Device (FAD) as a measure of perceived family function. Hierarchical linear regression analysis was used to determine the effect of family function on perceived self-efficacy while controlling for demographic factors (age, education, and income) and disability status. Results: None of the demographic variables included in the analysis were significant in predicting self-efficacy. Disability status was the largest predictor of MS self-efficacy (β = −0.657, P < .001). Family function was also a significant predictor of patient self-efficacy (β = −0.27, P = .002). After entering demographic variables and disability in step 1, the model accounted for 54% of total variance (R2 = 0.536). Model 2, which added family function, accounted for an additional 7% (R2Δ = 0.070). Conclusions: The variable in MS that most strongly predicts self-efficacy is MS-related disability. However, disability alone accounts for only half of the variance in patient self-efficacy, pointing to psychological factors as most likely to play an additional role in determining self-efficacy. Family function is one such psychological factor. It is therefore important for health-care providers to emphasize family involvement and education in compre-hensive treatment for MS patients.

Supported by: NoneDisclosure: Judith B. Levin, Gabriel Hoffnung, Lisa Glukhovsky, Jason Botv-inick, Vance Zemon: Nothing to disclose. Frederick W. Foley: Bayer (consulting fees).Keywords: Comprehensive care and MS, MS and the caregiver/family, Psycho-logical issues and MS

(CP22) VARIATION IN THE PERCEPTION OF FAMILY FUNCTION IN MULTIPLE SCLEROSIS AND ITS RELATIONSHIP WITH PATIENT SELF-EFFICACYGabriel Hoffnung,1 Judith B. Levin,2 Lisa Glukhovsky,1 Jason Botvinick,1 Vance Zemon,1 Frederick W. Foley3

1Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY; 2Levindale Hebrew Geriatric Center and Hospital, Baltimore, MD; 3Holy Name Medical Center, Teaneck, NJ

Background: Family and social support play a crucial role in helping patients with multiple sclerosis (MS) manage the significant practical and psychological burden of living with the disease. In this

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suggestive of an atypical form of MS many years before the diagno-sis was confirmed.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Imaging and MS, Natural history of MS, Psychological issues and MS

(CP25) BICAMS TABLET APPLICATION: A RELIABLE AND FAST WAY TO ASSESS COGNITIVE FUNCTIONINGMeghan Beier, Kevin Alschuler, Dagmar Amtmann, Katie Rutter, Christina Garcia, Sandra Reeves, Dawn Ehde

Department of Rehabilitation Medicine, University of Washington School of Medicine, Seattle, WA

Background: Up to 70% of individuals with multiple sclerosis (MS) experience cognitive dysfunction. Many clinicians use self-report as a way to screen for cognitive impairment. However, self-reported cognitive symptoms are highly correlated with emotional distress, rather than neuropsychological data, making objective tests the best way to detect and track cognition. Unfortunately, neuropsychological evaluations are time-consuming, expensive, and not universally avail-able. The Brief International Cognitive Assessment for MS (BICAMS) was developed by a team of cognition experts to give MS medical personnel a way to quickly assess and track cognitive symptoms. Although the intent of the BICAMS was to create a fast, intuitive assessment, the scoring and interpretation require precious clinic time and necessitate an understanding of psychometric information such as z scores and percentiles. We therefore created a BICAMS tablet application (“app”) to streamline and simplify administration and scoring. Objectives: To 1) test the reliability of a BICAMS app against the traditional paper version, 2) compare the time it takes to administer and score both forms, and 3) compare performance on the Rey Auditory Verbal Learning Test (RAVLT) and the California Verbal Learning Test–II (CVLT-II). Methods: This Consortium of Mul-tiple Sclerosis Centers (CMSC)–funded pilot study is in the process of enrolling 100 participants with MS. The study utilized two test administrators scoring participant responses simultaneously—one on the paper BICAMS and one on the BICAMS app. Half of the testing sessions are led by the paper administrator (Group A) and half by the app administrator (Group B). Although participants are only exposed to the material once, their responses are recorded on both administration methods. Unfortunately, Pearson would not grant permission for use of the CVLT-II in the app. We replaced it with the RAVLT, but also administered a paper CVLT-II to every participant. We will compare both list learning tasks to determine if the RAVLT is an efficacious substitution. Results: This study is under way. Preliminary analyses demonstrate promising results. No significant differences were found for scores obtained from either method of administration (tablet vs. paper), and there were no significant differences between the standard scores from the list learning tasks. However, there was a significant difference in total administration time (minutes) between the app (mean 27.09, SD 8.14) and paper-based (mean 14.17, SD 3.27) administrations; t34 = 11.03, P < .0001. Including scoring, administration of the paper-based BICAMS takes nearly double the amount of time as the app version. Conclusions: Preliminary find-ings suggest that the tablet application is a reliable and fast method for administering the BICAMS.

Supported by: CMSCDisclosure: Meghan Beier, Dagmar Amtmann, Katie Rutter, Christina Garcia, Sandra Reeves, Dawn Ehde: Nothing to disclose. Kevin Alschuler: Consortium of Multiple Sclerosis Centers, National Multiple Sclerosis Society, National Institute on Disability and Rehabilitation Research, PCORI (grant/research support).Keywords: Comprehensive care and MS, Neuropsychological assessment

(CP26) INCIDENCE OF ANXIETY IN PATIENTS WITH MULTIPLE SCLEROSISRivka Green,1 Jennifer Kalina,2 Krupa Pandey1

1Multiple Sclerosis Comprehensive Care Center, Barnabas Health, Livingston, NJ; 2MS Comprehensive Care Center, NYU Langone Medical Center, New York, NY

the McMaster Family Assessment Device (FAD), a measure of per-ceived family function. The MMSE offers measurements on the two subscales of self-efficacy function and self-efficacy control. Pearson r correlations were run to determine the relationship of disability and family function to general self-efficacy as well as to the subscales of self-efficacy control and self-efficacy function. Results: Self-efficacy function was more elevated (ie, worse) than self-efficacy control in a manner consistent with other research in MS (self-efficacy function, mean = 658.1, SD = 232.6; self-efficacy control, mean = 500.7, SD = 182.4). Disability (r = −0.724, P < .001) and family function (r = 0.354, P = .002) were both significantly correlated with overall MS self-efficacy. Disability was similarly correlated to both self-efficacy function (r = −0.642, P < .001) and self-efficacy control (r = −0.634, P < .001). Family function was also correlated with both self-efficacy function (r = −0.324, P = .004) and self-efficacy control (r = −0.313, P = .006). Conclusions: MS has a deleterious effect on patient self-efficacy, both in patient perception of functional ability (self-efficacy function) and in patient perception of personal locus of control (self-efficacy control). While both disability and family functioning are significantly related to self-efficacy, neither would suggest an explana-tion for the difference between self-efficacy function and self-efficacy control in MS.

Supported by: NoneDisclosure: Gabriel Hoffnung, Judith B. Levin, Lisa Glukhovsky, Jason Botv-inick, Vance Zemon: Nothing to disclose. Frederick W. Foley: Bayer (consulting fees).Keywords: MS and the caregiver/family, Psychological issues and MS

(CP24) APPEARANCE OF BALO’S CONCENTRIC SCLEROSIS 18 YEARS AFTER ACUTE PSYCHOSISAhmed Z. Obeidat, Aram Zabeti

Neurology and Rehabilitation Medicine, University of Cincinnati, Cincinnati, OH

Background: Balo’s concentric sclerosis (BCS) is a rare variant of multiple sclerosis (MS) and is characterized by findings of alternat-ing bands of demyelination and remyelination on brain magnetic resonance imaging (MRI). BCS is classically viewed as an acute and often life-threatening disease. Although MS can present as acute psychosis, BCS has been rarely described in psychotic patients. Objectives: To describe a case of relapsing-remitting MS with initial presentation as acute psychosis and later development of a BCS lesion on brain MRI. Methods: Case report and literature review. Results: A 15-year-old right-handed boy was institutional-ized for acute unexplained psychosis consisting of auditory and visual hallucinations in addition to grandiose delusions (eg, body is made of gold, ability to fly, and claims of prophecy). Patient had no known psychiatric disease or drug or substance use. At that time, cerebrospinal fluid (CSF) analysis was negative for infection or inflammation, and electroencephalography (EEG) was normal, but MRI showed white-matter disease within the internal capsule and the right parieto-occipital area. Tests for Wilson disease, porphyria, and lymphoma were all negative. The patient was then placed on lithium and discharged. Six months later, he presented with a second epi-sode of psychosis, for which he was admitted and successfully treat-ed. Ten years later, he developed unprovoked seizures. At that time, EEG showed mild slowing over the bilateral frontal head region, and MRI was highly suggestive of MS. CSF analysis revealed pleo-cytosis, elevated unmatched oligoclonal bands, and immunoglobulin G index. Workup for metachromatic leukodystrophy, sarcoidosis, and syphilis was negative. Thus, a diagnosis of MS was confirmed, and the patient was started on interferon beta. Eight years later, the patient presented with right homonymous hemianopia, and brain MRI showed multiple demyelinating lesions with one lesion consistent with BCS. Conclusions: BCS lesions can appear later in life in patients diagnosed with MS and can coexist with typical MS lesions. In agreement with recent reports, BCS can have a relatively benign clinical course and is not always fatal. Our patient’s unusual clinical presentation of acute psychosis followed by epilepsy syndrome was

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Posters: Epidemiology and Genetics

supplemental vitamin D intake, and body-mass index at age 18. We carried out analyses separately in each cohort and then calculated pooled RR estimates. Results: Women who reported 7 to 12 months per year of regular strenuous activity at ages 18 to 22 had a lower multivariable-adjusted rate of incident MS than those who reported no regular strenuous activity (RRpooled = 0.75; 95% CI, 0.58-0.98; P trend = .01). Physical activity at baseline was also inversely related to MS risk—compared with women in the lowest quintile of baseline physical activity, women in the highest quintile had a 30% reduced multivariable-adjusted rate of incident MS (RRpooled = 0.70; 95% CI, 0.54-0.90; P trend: .01). Conclusions: These findings suggest that greater physical activity is associated with lower MS risk. However, we were unable to adjust for confounding due to UV light exposure, a major source of vitamin D, and cannot rule out the possibility that women reduce their physical activity in response to pre-clinical MS.

Supported by: National Institutes of HealthDisclosure: Kirsten S. Dorans: National Institutes of Health (grant/research support). Jennifer Massa: Nothing to disclose. Tanuja Chitnis: Novartis, Biogen Idec, Merck Serono (grant/research support). Alberto Ascherio, Kassandra Munger: National Institutes of Health, National Multiple Sclerosis Society (grant/research support).Keywords: Epidemiology of MS, Etiology of MS

(EG02) TEMPORAL CHANGES IN THE AGE AT MULTIPLE SCLEROSIS ONSET: IMPORTANCE OF CONTROLLING FOR EQUAL OBSERVATION TIMEMihaela D. Pirvoaica,1 Afsaneh Shirani,1 Elaine Kingwell,1 Feng Zhu,1 Yinshan Zhao,1 John D. Fisk,2 Ruth Ann Marrie,3 Virender Bhan,4 Robert L. Carruthers,1 Helen Tremlett5

1Neurology, University of British Columbia, Vancouver, BC, Canada; 2Psychiatry, Dalhousie University, Halifax, NS, Canada; 3Medicine, University of Manitoba, Winnipeg, MB, Canada; 4Medicine (Neurology), Dalhousie University, Halifax, NS, Canada; 5University of British Columbia, Vancouver, BC, Canada

Background: Previous studies have examined whether changes in the age at multiple sclerosis (MS) onset have occurred over time, but findings have been inconsistent. If a substantial change has occurred, it could have important implications for health-care planning and may indicate shifts in environmental etiologic factors. However, it is challenging to assess these trends; for example, when comparing recent birth cohorts to earlier birth cohorts, spurious findings may result if insufficient time is allowed for individuals from the recent birth cohort to develop MS. Objectives: We investigated temporal trends in age at onset in MS patients from three Canadian provinces, and assessed the impact of controlling for equal observation time between birth cohorts. Methods: Data from the MS clinic databases in British Columbia (BC), Manitoba (MB), and Nova Scotia (NS) were accessed. Patients with definite MS (Poser or McDonald criteria) were grouped by birth year (1941–1980) into 5-year blocks. Trends in the age at onset of MS were assessed using linear regression adjusted for sex. Initially all MS patients were included (the broad cohort), and then a restricted cohort was created to allow compara-ble observation times for each birth cohort, in which all patients had reached at least age 40 (80th percentile for onset age) by study end (12/31/2007) and had MS onset by age 40. Results: A total of 9459 MS patients were included (BC = 5423, MB = 1419, and NS = 2617). In the broad cohort, there was an apparent steep decline in the age at onset: from 37.0 ± 10.8 years for the earliest birth group (1941–1945) to 28.0 ± 6.4 years for the 1966–1970 birth group and 23.3 ± 4.2 for the most recent birth group (1976–1980), with a mean average decrease of 2.0 years in age at onset between each consecutive birth group (P < .001). In the restricted cohort (n = 6003), a statistically significant decrease in the mean age at onset was still evident (30.0 ± 6.7 years for the earliest birth group and 28.3 ± 6.0 years for the 1966–1970 birth group; P < .001); how-ever, the decrease in average age was considerably smaller at 0.3 years between each consecutive birth group. Conclusions: These time-restricted analyses, using three large MS clinic databases, sug-gest a small decrease in onset age over 4 decades of birth cohorts. Findings also demonstrate how apparent changes in the age at MS

Background: The exact incidence of anxiety in multiple sclerosis (MS) varies in the literature but is estimated to be 44.5%. Although research has shown that patients newly diagnosed experience higher anxiety levels, the relationship between anxiety and disease duration is unclear. Since anxiety can be comorbid with depression in MS populations, it is relevant to establish its association. Although anxi-ety typically increases with older age, research on this relationship in MS populations is inconclusive. Objectives: To investigate the incidence of anxiety in an outpatient MS center with the predictors disease duration, depression, and age while controlling for disabil-ity status. Methods: The Hospital Anxiety and Depression Scale (HADS), which has demonstrated good reliability and validity when performed in outpatient settings, was distributed once to MS patients over 3 months to assess anxiety and depression. Patient-Determined Disease Steps (PDDS) scores determined disability status. Disease duration and age were confirmed by neurologists. Results: Out of 160 patients with MS who completed the HADS, 19% reported abnormal anxiety, 14% reported borderline cases, and 67% did not report anxiety. Disease duration was mildly inversely related to anxiety, depression and anxiety scores were positively correlated, and age was inversely related to anxiety. The control predictor vari-ables were significantly related to this outcome (R2 = 0.35, F4,144 = 19.26, P < .001). The standardized partial regression coefficients indicated two statistically significant predictors, depression (β = 0.55, P < .001) and age (β = −0.25, P < .001). These results indicate that both higher depression scores and younger age sig-nificantly and independently affected anxiety in this population, while controlling for the effects of other predictors in this regression model. Conclusions: 33% of patients reported symptoms of anxiety, emphasizing the need to focus on treating anxiety, especially early in one’s disease course. Clinicians should recognize that elevated depression scores can predict higher anxiety levels. Lastly, in our cohort, younger age predicted higher anxiety levels, demonstrating that progressive illnesses may affect younger populations more. Since approximately one-third of patients with MS expressed anxiety symp-toms, it is important to incorporate this into treatment plans.


EPIDEMIOLOGY AND GENETICS

(EG01) PHYSICAL ACTIVITY AND THE INCIDENCE OF MULTIPLE SCLEROSISKirsten S. Dorans,1 Jennifer Massa,1 Tanuja Chitnis,2 Alberto Ascherio,1 Kassandra Munger1

1Harvard School of Public Health, Boston, MA; 2Massachusetts General Hospital for Children, Boston, MA

Background: There is some evidence that exercise might modify disease progression in individuals with multiple sclerosis (MS), but little research has focused on whether physical activity is associated with the incidence of MS. Objectives: To study whether physical activity at multiple points in life is associated with a lower rate of incident MS in two large cohorts of women, the Nurses’ Health Study (NHS; n = 121,701) and the Nurses’ Health Study II (NHSII; n = 116,430). Methods: Women reported information on recent physi-cal activity in 1986 (NHS) and 1989 (NHSII) and on selected follow-up questionnaires. After excluding participants with missing or incom-plete baseline physical activity information and those diagnosed with MS before baseline, there were 82,978 women in NHS (follow-up 1986–2004) and 116,002 women in NHSII (follow-up 1989–2009). Participants also reported early-life activity. There were 568 confirmed MS cases with MS diagnosis after baseline (117 in NHS, 451 in NHSII). To estimate relative rates (RRs) and 95% confidence intervals (CIs), we used Cox proportional hazards models, adjusting for age, latitude of residence at age 15, ethnicity, cigarette smoking,

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Background: Dimethyl fumarate (DMF) has been associated with lymphopenia in clinical trials. This is particularly relevant in light of a recent case of progressive multifocal leukoencephalopathy in a lymphopenic patient on DMF. Lymphopenia occurred in approxi-mately 41% of trial subjects. Lymphocyte counts typically reached nadir at 1 year and remained stable. DMF was not discontinued in trials solely due to lymphopenia. Patient and clinician conversations at the start of DMF treatment often focus on common side effects and tolerability and may de-emphasize lymphopenia and risk of infection. Objectives: 1) Describe incidence, time of onset, and degree of lymphopenia associated with use of DMF in University of Rochester Multiple Sclerosis Clinic patients. 2) Compare our practical clinical experience with that of the clinical trials to better inform our patients about risk and monitoring on DMF. Methods: A retrospective chart review was conducted for all clinic patients who completed DMF enrollment forms between April 2013 and September 2014. Factors reviewed included demographics, DMF duration, blood counts, and discontinuation rates. Basic descriptive statistical analyses were com-pleted. Results: Of 228 patients prescribed DMF, 152 remained on medication for >3 months and had at least one follow-up lymphocyte count. Lymphopenia (absolute lymphocyte count [ALC] <0.91 × 109/L) occurred in 35.5% of our patients during DMF treatment: 3.9% grade 3, 17.1% grade 2, and 14.5% grade 1. ALC primarily remained stable after reaching nadir. Mean duration of DMF treat-ment when lymphopenia was first identified was 7.5 months. Of the lymphopenic patients, more than one-third developed the lympho-penia within the first 6 months. 7.2% of patients discontinued DMF due to lymphopenia, the majority with ALC <0.6. Conclusions: Incidence of lymphopenia described in our clinical practice to date is similar to that described in the clinical trials. It was frequently identi-fied in patients soon after DMF initiation, supporting the practice of monitoring blood counts earlier and educating patients on the impor-tance of follow-up bloodwork. While the risk of opportunistic infec-tions is likely the result of more prolonged lymphopenia, the ALC in DMF does not tend to resolve. Early detection of lymphopenia allows increased time for therapeutic decision-making and more informed risk/benefit discussions with patients.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Dimethyl fumarate, Disease-modifying treatments in MS, Epidemiol-ogy of MS

(EG05) CLINICAL COURSE OF RELAPSING-REMITTING MULTIPLE SCLEROSIS IN NONWHITE MS PATIENTSMitzi J. Williams,1 Stephen Krieger,2 Angel Chinea,3 Aljoeson Walker,4 Jennifer Smrtka,5 Eileen O’Connor,6 Terrie Livingston,6 Xiaojun You,6 Leslie Meltzer6

1Multiple Sclerosis Center of Atlanta, Atlanta, GA; 2Icahn School of Medicine, Corinne Goldsmith Dickinson Center for Multiple Sclerosis, New York, NY; 3San Juan Multiple Sclerosis Center, Guaynabo, PR; 4Department of Neuroscience, Medical University of South Carolina, Charleston, SC; 5South Florida Neurology Associates, Boca Raton, FL; 6Biogen Idec, Cambridge, MA

Background: A growing body of literature suggests that there may be differences in multiple sclerosis (MS) baseline character-istics/severity across ethnic groups. Most data are derived from registries or individual practices, but detailed clinical trial data are limited. Objectives: Describe baseline characteristics and MS clinical course in white and nonwhite subjects from six random-ized, placebo-controlled trials. Methods: Subjects randomized to placebo from the MSCRG, AFFIRM, DEFINE, CONFIRM, SELECT, and ADVANCE studies were grouped into four racial/ethnic groups: white, black, Asian, and Hispanic. Baseline characteristics and clini-cal/radiologic outcomes were evaluated (white subjects as reference group). Hispanic status was collected only in AFFIRM; thus these subjects (n = 22) were not included in the analyses. Results: In total, 1655 white, 29 black, and 141 Asian subjects were included in the analysis. Baseline demographic and disease characteristics were similar between black and white subjects. Compared with white

symptom onset between birth groups over time can be significantly inflated without due consideration of comparable observation time.

Supported by: NoneDisclosure: Mihaela D. Pirvoaica: Genentech (grant/research support). Afsaneh Shirani: Multiple Sclerosis Society of Canada, Canadian Institute of Health Research, National Multiple Sclerosis Society (grant/research support). Elaine Kingwell, Feng Zhu, Yinshan Zhao, John D. Fisk, Robert L. Carruthers, Helen Tremlett: Nothing to disclose. Ruth Ann Marrie: Sanofi-Aventis (conduct of clini-cal trial). Virender Bhan: Biogen Idec, EMD Serono, Genzyme, Novartis, Teva, Roche (consulting fees).Keywords: Age at onset of MS, Epidemiology of MS

(EG03) COHABITATION IS ASSOCIATED WITH LOWER LEVELS OF CLINICAL DISABILITY IN MULTIPLE SCLEROSISKatelyn S. Kavak,1,2 Barbara E. Teter,1-3 Karen Zakalik,1,2 Bianca Weinstock-Guttman1-3

1New York State MS Consortium, Buffalo, NY; 2Jacobs MS Center of Treatment and Research, Buffalo, NY; 3Department of Neurology, University at Buffalo, Buffalo, NY

Background: The protective effects of social support have been well documented in other diseases such as cancer, in which mar-ried patients had a longer mean survival time than those who were single. In multiple sclerosis (MS), most social support studies have been limited to quality of life. Supportive assistance for MS patients is often provided by a spouse or partner. Objectives: To investigate if there were any differences in disability measures between MS patients living alone compared to those living with a spouse or partner. Methods: A total of 4371 MS patients between the ages of 25 and 50 were extracted from the NYSMSC registry. Of those, 726 (16.6%) lived alone, while 3645 (83.4%) lived with a spouse or partner. ANOVA analysis was conducted to investigate the association of living status with Timed 25-Foot Walk (T25FW) and Expanded Disability Status Scale (EDSS). An interaction term with gender was added to explore male- and female-specific effects. Results: The mean age in our sam-ple was 39.6 (6.3), and 3194 (73.1%) were female. MS patients liv-ing alone had significantly higher EDSS scores (3.6 ± 2.3) compared to those living with a significant other (2.9 ± 2.0, P < .001). The time to complete the T25FW was also significantly longer for those living alone (30.0 ± 58.2 vs. 18.4 ± 43.5, P < .001). The gender by living status interaction term was significant for both EDSS (P = .012) and T25FW (P = .002). Males living alone had an EDSS of 4.1 (2.4) com-pared to cohabitating males of 3.1 (2.0), while female MS patients living alone had a mean EDSS of 3.4 (2.1) compared to 2.8 (2.0) for those living together. Male MS patients living alone had a mean T25FW time of 39.1 seconds (66.8), more than twice as long as that of males who lived with a spouse or partner (18.2 ± 43.3), a result that was less notable in females (26.0 ± 53.5 living alone vs. 18.5 ± 43.7 living together). Conclusions: MS patients living alone had significantly higher EDSS scores, and took a longer time to complete the T25FW ambulation test compared to those living together. Social support, often provided by a partner, has been found to be associated with increased medication adherence and psychological well-being. Results stratified by sex showed that males living alone experienced worse levels of disability than females living alone. Studies have shown that women generally have larger social networks and may therefore rely less on caregiver support than men.

Supported by: NoneDisclosure: Katelyn S. Kavak, Karen Zakalik: Nothing to disclose. Barbara E. Teter: Biogen Idec, Teva Neurosciences, EMD Serono, Avanir, Genzyme, Novar-tis (grant/research support). Bianca Weinstock-Guttman: Biogen Idec, Teva Neu-rosciences, EMD Serono, Pfizer, Novartis, Questcor, Genzyme, Mylan, Acorda (consulting fees); Biogen Idec, Teva Neurosciences, EMD Serono, Pfizer, Novartis, Questcor, Genzyme, Mylan, Acorda, Shire (grant/research support).Keywords: Epidemiology of MS, MS and the caregiver/family, Social support

(EG04) DIMETHYL FUMARATE–ASSOCIATED LYMPHOPENIA IN CLINICAL PRACTICE: IMPLICATIONS FOR INFORMED PATIENT MANAGEMENTJessica F. Robb, Megan Hyland, Lawrence Samkoff

Neurology, University of Rochester, Rochester, NY

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−0.65, P < .001 for climbing stairs). T25FW was also significantly correlated to all three subjective measures (r = 0.60, P < .001 for lower-limb functioning, r = −0.66, P < .001 for getting up, and r = −0.64, P < .001 for climbing stairs). Conclusions: High correla-tions demonstrate that EDSS detects ambulation disability similar to patients’ real-life experience. Lower isolated PFSS correlations may be indicative of nonmotor impairment contributions to ambulation limitation. Results further underscore the value of PRO as a reliable and efficient tool in assessing disability and impact on activities of daily living.

Supported by: None

Disclosure: Barbara E. Teter: Biogen Idec, Teva Neurosciences, EMD Serono, Avanir, Genzyme, Novartis (grant/research support). Katelyn S. Kavak: Noth-ing to disclose. Channa Kolb-Sobieraj: Biogen, EMD Serono (fees for non-CME services from commercial interests or their agents); Teva (consulting fees). Bianca Weinstock-Guttman: Biogen Idec, Teva Neurosciences, EMD Serono, Pfizer, Novartis, Questcor, Genzyme, Mylan, Acorda (consulting fees); Biogen Idec, Teva Neurosciences, EMD Serono, Pfizer, Novartis, Questcor, Genzyme, Mylan, Acorda, Shire (grant/research support).

Keywords: Comprehensive care and MS, Disability, Management of activities of daily living in MS

(EG07) THE 2D:4D RATIO, A PROXY FOR PRENATAL ANDROGEN LEVELS, DIFFERS IN MEN WITH MULTIPLE SCLEROSISRiley Bove,1,2 Muhammad T. Malik,2 Camilo Diaz-Cruz,2 Alicia Chua,2 Taylor Saraceno,2 David Bargiela,2 Emily Greeke,2 Bonnie I. Glanz,2 Brian C. Healy,3 Tanuja Chitnis4

1Neurology, Harvard Medical School, Boston, MA; 2Partners Multiple Sclerosis Center, Brigham and Women’s Hospital, Brookline, MA; 3Biostatistics Center, Massachusetts General Hospital, Boston, MA; 4Massachusetts General Hospital for Children, Boston, MA

Background: The prenatal period is increasingly understood as a period of vulnerability to subsequent development of multiple sclero-sis (MS). The ratio of an individual’s second and fourth digit lengths (2D:4D) reflects digit growth that is highly influenced by the ratio of prenatal androgen to estrogen levels (PNAS. 2011;108:16289). In MS, low testosterone has been linked with MS risk in adult men, but the effect of prenatal androgen levels on susceptibility to autoim-mune diseases has not been explored. Objectives: To assess the hypothesis that the 2D:4D ratio is increased in men with MS rela-tive to men without MS. Secondarily, to assess whether the 2D:4D ratio in men with MS is associated with clinical features of a more aggressive course. Methods: We obtained digital scans of the right hand for 138 men with MS and 145 men without autoimmune disease (non-MS). All individuals were aged 18 to 65 years, were right-handed, and reported no prior hand trauma. Digit length was calculated using digital calipers. Our primary statistical analysis was a cross-sectional comparison of the 2D:4D ratio between MS subjects and HCs using two-sample t test. Results: The mean (SD) 2D:4D ratio was higher in MS (0.9548 [0.040]) than in non-MS subjects (0.9456 [0.0324]) (P = .035). These findings remained significant after we adjusted for age and race. In MS subjects, the 2D:4D ratio was not correlated with MS type, age at first symptoms, or MS Severity Score (P > .40 for each), nor was it correlated with adult testosterone levels in a subset of 52 men (r = 0.056, P = .69). Con-clusions: In this study, male MS patients had a higher 2D:4D ratio than men without MS, suggestive of lower prenatal androgen levels. These findings support an emerging role of low androgens during key developmental periods as a risk factor for MS.

Supported by: National Multiple Sclerosis Society/AAN

Disclosure: Riley Bove, Muhammad T. Malik, Alicia Chua, Taylor Saraceno, David Bargiela, Emily Greeke: Nothing to disclose. Camilo Diaz-Cruz, Bonnie I. Glanz: Merck Serono (grant/research support). Brian C. Healy: Merck Serono, Novartis (grant/research support). Tanuja Chitnis: Novartis, Biogen Idec, Merck Serono (grant/research support).

Keywords: Epidemiology of MS, Etiology of MS, Testosterone

subjects, Asian subjects had a significantly lower mean age (34.3 vs. 37.2 years), higher mean EDSS score (2.8 vs. 2.5), higher mean number of relapses in the prior year (1.6 vs. 1.4), shorter duration of MS (5.7 vs. 7.5 years), and a lower proportion of those previously treated with disease-modifying therapy (DMT; 22.0% vs. 33.2%). Over the studies’ duration, black subjects had a higher risk of EDSS progression (hazard ratio [95% CI]: 3.6 [2.02-6.45]; P < .0001) and significantly greater mean changes from baseline versus white subjects in EDSS score at year 1 (0.6 vs. 0.1) and year 2 (1.1 vs. 0.3). No significant differences were observed in relapse endpoints between white and nonwhite subjects, except for a trend for a higher adjusted annualized relapse rate in black versus white subjects (rate ratio [95% CI]: 1.65 [0.95-2.87]; P = .0749). Conclusions: In this analysis of placebo-treated subjects from six MS clinical trials, several differences were noted between nonwhite and white subjects. Over the course of the studies, baseline disease seemed to be more severe in the Asian population and disability outcomes were worse in black versus white subjects. Interpretation of results is methodologically lim-ited by pooling across trials and low numbers of nonwhite subjects. These results highlight the need to increase recruitment of nonwhite subjects into MS clinical trials to gain better understanding of disease activity and response to DMT in these populations.

Supported by: Biogen IdecDisclosure: Mitzi J. Williams: Biogen Idec, Novartis, Bayer, Acorda, Mallinck-rodt, Genzyme, Teva Neuroscience, EMD Serono (fees for non-CME services from commercial interests or their agents); Biogen Idec, Novartis, Bayer, Genzyme, Teva Neuroscience (consulting fees). Stephen Krieger: Acorda, Bayer HealthCare, Biogen Idec, EMD Serono, Genzyme, Questcor, Teva Neuroscience (consulting fees). Angel Chinea: Biogen Idec, Novartis, Teva, Allergan, Mallinckrodt, Gen-zyme, Acorda (consulting fees). Aljoeson Walker: Genzyme, Bayer, Biogen, Teva (consulting fees). Jennifer Smrtka: Biogen Idec, Mallinckrodt (consulting fees); Genzyme, Mallinckrodt, Teva Neuroscience (fees for non-CME services from com-mercial interests or their agents). Eileen O’Connor, Terrie Livingston, Xiaojun You, Leslie Meltzer: Biogen Idec (salary).Keywords: Epidemiology of MS, Genetics and MS, Natural history of MS

(EG06) EDSS PYRAMIDAL FUNCTION SCORE CORRELATIONS WITH OBJECTIVE AND SUBJECTIVE MEASURES OF AMBULATIONBarbara E. Teter,1-3 Katelyn S. Kavak,1,2 Channa Kolb-Sobieraj,2,3 Bianca Weinstock-Guttman1-3

1New York State MS Consortium, Buffalo, NY; 2Jacobs MS Center of Treatment and Research, Buffalo, NY; 3Department of Neurology, State University of New York at Buffalo, Buffalo, NY

Background: Ambulation impairment limits daily activities and reduces quality of life for patients with multiple sclerosis (MS). Patient-reported outcome (PRO) measures of limb functioning, get-ting up from a sofa, and climbing stairs could provide efficient and reliable indicators of clinical status. The Kurtzke EDSS pyramidal functional system score (PFSS) has been shown to detect disability progression in clinical trials. Objectives: To investigate the correla-tion between objective measures of ambulation by the EDSS-PFSS, Timed 25-Foot Walk (T25FW), and subjective measures by patient self-report. Methods: A sample of 9000 patients was extracted from the New York State Multiple Sclerosis consortium (NYSMSC). Objective measures included EDSS as well as its PFSS, and T25FW. Subjective measures were collected utilizing the validated LIFE-wareSMPRO assessment for patients to self-report 1) lower-limb limita-tion, 2) getting up from a chair, and 3) climbing stairs. Correlations were assessed using the Spearman rank correlation coefficient (r). Results: Mean EDSS and PFSS scores were 3.5 (2.3) and 1.9 (1.5), respectively, while the average time to complete the T25FW was 30.2 seconds (57.8). Strong correlations were found between overall EDSS scores and self-reported lower-limb functioning (r = 0.73, P < .001), getting up (r = −0.72, P < .001), and climbing stairs (r = −0.73, P < .001), with slightly lower correlations found for PFSS scores and the subjective measures (r = 0.67, P < .001 for lower limb functioning; r = −0.64, P < .001 for getting up; and r =

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Posters: Neuroimaging

(EG09) A COMPREHENSIVE REVIEW OF MULTIPLE SCLEROSIS IN IRANMaziar Eslami Farsani

National Multiple Sclerosis Society, Irvine, CA

Background: Multiple sclerosis (MS) is a chronic demyelinating dis-ease of the central nervous system that usually affects young adults. Observations have shown that the prevalence of MS is variable among different populations and geographic areas. Recent studies also mentioned a huge increase of MS incidence and prevalence among Iranians in the last decade. Objectives: The aim of this study was to classify clinical features, environmental factors, and migration effect on MS in Iranians and also to suggest possible rea-sons for the increasing rate of MS among this population. Methods: A systematic search of all English-language literature (indexed in PubMed) concerning MS in Iranians around the world, from the early 1970s to 2014. The keywords used were multiple sclerosis, Iran, and Iranians. Results: The initial electronic search identified 367 publications, most of which were eliminated (due to our time, and language exclusion criteria and repetitive data). Finally, 31 articles fulfilled the inclusion criteria and were used as the basis of the study. Conclusions: Available data show high incidence and prevalence of MS (mostly the relapsing-remitting form) in Iranians recently, with some specific clinical characteristics (eg, high female preponder-ance). Certain types of MS such as early-onset are frequent, while the primary progressive and late-onset types are less common. Besides some associations with infectious agents such as Epstein-Barr virus, Iranian MS patients have low serum levels of vitamin D. Iranians migrating to areas with a higher risk of MS and Parsis (Iranian/Zoro-astrians) living in India have higher MS rates (versus other Indians) even after 100 years of immigration. Genetic factors and environ-mental factors related to lifestyle, a large migration effect, ethnicity, and cultural behaviors such as marrying close kin may be involved.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Epidemiology of MS

NEUROIMAGING

(NI01) TUMEFACTIVE DEMYELINATING LESION OF SPINAL CORD DUE TO AQUAPORIN-4 ANTIBODYZubeda B. Sheikh, Weizhen Wang, Bhrugav Raval, Weredeselam Olango, Machteld E. Hillen

Neurology, Rutgers-NJMS, Newark, NJ

Background: Tumefactive demyelinating lesions (TDLs) are lesions that do not exhibit classic presentation and are indistinguishable from neoplasm on imaging studies. TDLs are rare and typically seen in brains of patients with multiple sclerosis (MS). Seven case reports of an isolated spinal cord TDL exist in the literature, but the occurrence of spinal cord TDL in neuromyelitis optica (NMO) has not been previ-ously reported. Objectives: To report a case of NMO that present-ed as a TDL in spinal cord. Methods: A 43-year-old woman with morbid obesity and developmental delay presented with progressive right leg and handgrip weakness of 2 weeks’ duration. On magnetic resonance imaging (MRI), increased T2 signal was noted in cervical spinal cord from the C5 to C7 vertebral level with poorly demar-cated boundaries, focal enlargement at C6-C7, and homogeneous enhancement. The imaging features were consistent with a neoplasm such as astrocytoma or ependymoma, and myelitis was thought to be unlikely. For definitive diagnosis, she underwent a C5-C7 pos-terior laminectomy with biopsy of the lesion that showed inflamma-tory macrophages with myelin and related products, consistent with demyelination. Brain MRI showed an occasional periventricular FLAIR hyperintensity. She was treated with pulse high-dose steroids with good improvement and was lost to follow-up. Results: The patient

(EG08) VASCULAR COMORBIDITIES AMONG PATIENTS WITH MULTIPLE SCLEROSIS AT A COMPREHENSIVE CARE CENTERElizabeth W. Triche,1,2 Lindsay O. Tuttle,1 Jennifer A. Ruiz,1 Carolyn J. St. Andre,1 Albert C. Lo3

1Mandell Center for Multiple Sclerosis, Mount Sinai Rehabilitation Hospital, Hartford, CT; 2Department of Epidemiology, Brown University School of Public Health, Providence, RI; 3Departments of Neurology and Engineering, Brown University, Providence, RI

Background: A progressive and potentially debilitating disease, multiple sclerosis (MS) often presents with various physical and cogni-tive impairments. Comorbidities in the MS population are important, as they may contribute to MS disease progression, reduced qual-ity of life, and unfavorable health outcomes. It is therefore relevant to estimate the prevalence of comorbid conditions in people with MS. Vascular comorbidities (Vcom), including diabetes (DM), hypertension (HTN), high cholesterol (HCL), and stroke (CVI), are of significance in people with MS, as they have been shown to be factors in increasing cognitive decline and brain atrophy. In addition, Vcom have been correlated with increased disability progression in MS. Objectives: To estimate the age-specific prevalence of Vcom in a community sample of MS patients (CSMS), and compare it with that in the general population (GP). Methods: Retrospective chart review was carried out on 200 people with MS (CSMS) seen at a comprehensive care center. Inclusion criteria consisted of having an EDSS evaluation performed by a physician assistant between October 2011 and January 2013. Data collected by the physician assistant included patient demographics, disease history, and history of Vcom, including DM, HTN, HCL, and CVI. Age-specific data for each of the Vcom were evaluated and compared to GP (CDC) data, stratified by gender. Data were analyzed using SPSS version 18. Because of small numbers of people with MS in our chart review over the age of 64, we focused on ages up to 74. Results: Participants in the CSMS (n = 149 female; n = 51 male) were between 17 and 80 years of age (mean 44.9, SD 12.3), with a disease duration of 0 to 42 years (mean 7.7, SD 9.3) and BMI between 18.9 and 54.3 (mean 28.3, SD 6.8). Rates of Vcom in the CSMS (n = 200) were similar to those in the GP. Among women, rates of HTN were lower for each age group (4.1% vs. 8.7% and 25.0% vs. 39.5% in the 20–44 and 45–64 age groups, respectively), of DM in the 0–44 age group were higher for CSMS (4.1%) than GP (1.7%), and of HCL in the 45–64 age group were lower for CSMS (23.5%) than GP (42.4%); other age-specific rates were similar. Among men, dif-ferences between rates of HTN and HCL in the CSMS were similar to those in the GP. Rates of DM in the CSMS were somewhat lower than in the GP for each age group. Conclusions: Among women and men, age-specific rates of vascular comorbidities in people with MS may be lower than or similar to rates in the general US population.

Supported by: None

Disclosure: Elizabeth W. Triche: Mount Sinai Rehabilitation Hospital, rEVO Pharmaceuticals (consulting fees); Mount Sinai Rehabilitation Hospital (travel reimbursement); National Institutes of Health, National Multiple Sclerosis Soci-ety, Acorda Therapeutics Inc (grant/research support). Jennifer A. Ruiz: National Multiple Sclerosis Society, Acorda Therapeutics Inc (grant/research support). Lindsay O. Tuttle, Carolyn J. St. Andre: Nothing to disclose. Albert C. Lo: Acorda Therapeutics Inc, National Multiple Sclerosis Society (advisory board); Acorda Therapeutics Inc, National Multiple Sclerosis Society, Veterans Administration (grant/research support); Consortium of Multiple Sclerosis Centers (honorarium); National Multiple Sclerosis Society, Consortium of Multiple Sclerosis Centers (travel reimbursement).

Keywords: Comorbidities, Epidemiology of MS

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Posters: Epidemiology and GeneticsPosters: Neuroimaging

and these could be assessed in future longitudinal examinations and clinical trials of motor rehabilitation.

Supported by: NoneDisclosure: Elizabeth A. Hubbard, Nathan C. Wetter, Bradley P. Sutton, Robert W. Motl: Nothing to disclose. Lara A. Pilutti: National Multiple Sclerosis Society (grant/research support).Keywords: Imaging and MS, Walking performance

(NI03) COGNITION AND EARLY THALAMIC ATROPHYRobert T. Naismith,1 Vaishak A. Amblee,1,2 Samantha Lancia1

1Department of Neurology, Division of Neuroimmunology, Washington University School of Medicine in St. Louis, St. Louis, MO; 2University of Illinois at Chicago College of Medicine, Chicago, IL

Background: Cognitive deficits are seen in about 20% of all relapsing-remitting multiple sclerosis (MS) patients. Studies indicate that in addition to cortical lesions, gray-matter atrophy, specifically atrophy of deep brain structures like the thalamus, may be involved in cognitive impairment. Objectives: This study attempted to deter-mine the relationships between neurocognitive testing and changes in thalamic volume in MS patients over a 2-year disease period. Meth-ods: 75 MS patients underwent a comprehensive cognitive battery at month 0, 6, 12, and 24. Brain magnetic resonance imaging (MRI) with contrast was performed monthly. Cognitive domains assessed included information processing speed, visual-spatial/executive func-tion, and verbal memory/attention. A single trained observer (IRR = 0.988) manually outlined thalamic volumes on axial MRI scans using the T2- and proton density–weighted images to determine the percent volume change over 2 years. The percent change in thalamic volumes were evaluated for relationships with neurocognitive testing. Results: For up to 2 years, 65 subjects experienced a decrease in thalamic volume, 5 demonstrated stability in thalamic volume, and 5 were stable. For those with thalamic atrophy, mean change from baseline to last scan was −8.4%. Changes in each cognitive test over 2 years did not correspond to rates of thalamic atrophy. For those with early decreases in processing speed as assessed by the WAIS Symbol Search over the first 12 months, there was a relation-ship between worsening processing scores and atrophy (r = 0.38, P = .003). However, from 12 through 24 months, processing speed stabilized or improved with treatment, whereas thalamic volumes continued to decline. Conclusions: For subjects recently diagnosed with active MS, initiation of disease-modifying therapy can be associ-ated with stabilization or improvement in cognitive testing over the first 6 to 12 months. However, thalamic atrophy may continue over the first 2 years. This may suggest a lag period from when cognition improves and thalamic volumes stabilize, possibly due to continued neurodegeneration. Long-term data past 2 years would help deter-mine when rates of thalamic atrophy stabilize with treatment.

Supported by: NoneDisclosure: Robert T. Naismith: Acorda, Bayer, Biogen, Genzyme, Novartis, Questcor (consulting fees). Vaishak A. Amblee, Samantha Lancia: Nothing to disclose.Keywords: Cognition and MS, Imaging and MS, Psychological issues and MS

(NI04) DELAYED TUMEFACTIVE DEMYELINATION IN A PATIENT WITH MENINGIOMA AND OPTIC NEURITIS: CASE REPORT AND REVIEW OF THE LITERATUREAhmed Z. Obeidat, Aram Zabeti

Neurology and Rehabilitation Medicine, University of Cincinnati, Cincinnati, OH

Background: Brain meningiomas (MGMs) can be associated with visual disturbances. However, acute optic neuritis (ON) is rarely encountered. Radiotherapy is frequently used as a treatment modal-ity. Cases of de novo multiple sclerosis (MS) or exacerbation of an existing disease have been previously described following brain irradiation. The mechanism is thought to be related to localized or diffuse blood-brain barrier disruption and inflammation. Objectives: To present a case of a woman who initially presented with ON, was

presented with a relapse involving her cervical spinal cord 2 months after her initial presentation and was treated with high-dose steroids and plasmapheresis. Her workup for MS mimics, drawn during her initial admission, was remarkable only for a positive aquaporin-4 antibody. Rituximab was started for disease modification. We con-tinue to follow the patient. Conclusions: TDLs are rare and usually occur in the brain of patients with MS. TDLs are more common in women, with an average age of presentation of 37 years. Their occurrence in spinal cord has been reported in MS but not in NMO. TDLs pose a diagnostic challenge, and patients usually undergo a biopsy/excision to obtain a definite diagnosis. Advanced imaging in the form of MR perfusion and MR spectroscopy may be helpful in diagnosis of patients with TDL in the brain and in avoiding surgical intervention. However, in the cord, due to decreased tissue volume, these tests are not helpful. Relapsing-remitting course, presence of periventricular lesions in brain, and response to steroids might help in diagnosis. Differentiating these lesions from tumors is important to avoid erroneous surgical procedures and treatment such as radiation, which can worsen demyelinating disease and put patients at risk for secondary malignancies.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Imaging and MS, Tumefactive demyelinating lesion

(NI02) DIFFUSION TENSOR IMAGING OF THE CORTICOSPINAL TRACT AND WALKING OUTCOMES IN MULTIPLE SCLEROSISElizabeth A. Hubbard,1 Nathan C. Wetter,2 Lara A. Pilutti,1 Bradley P. Sutton,2 Robert W. Motl1

1Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL; 2Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL

Background: Diffusion tensor imaging (DTI) reflects restrictions to diffusion and quantifies disruptions and damage to white matter along the corticospinal tract. Research has identified a significant relationship between DTI indices in the corticospinal tract and dis-ability status in people with multiple sclerosis (MS). To date, little is known about the association between DTI indices of the cortico-spinal tract with walking and gait outcomes in MS. Such inquiry is essential for examining the integrity of white-matter pathways as a possible mechanism of walking changes in MS. Objectives: This study examined the associations among DTI indices (fractional anisotropy [FA], radial diffusivity [RD], and axial diffusivity [AD]) of the corticospinal tract with walking and gait outcomes in people with MS. Methods: We enrolled 58 people with MS who underwent 3T brain magnetic resonance imaging (MRI) examination including anatomic and DTI acquisitions. We examined white-matter structural integrity in the corticospinal tract in the brain with DTI. Motor path-ways were identified using tractography to identify the fiber tracts propagating from motor cortex to the midbrain. FA, RD, and AD values were calculated by averaging the respective FA, RD, and AD value for each voxel on the resulting tracts and weighting this value by the probability of a fiber tract passing through that voxel. Measures of FA, RD, and AD for the fiber pathways were created for each hemisphere of the brain that were then averaged to produce a single value for each index. Participants also completed three walking performance assessments: 6-Minute Walk (6MW), Timed 25-Foot Walk (T25FW), and gait testing. We examined associations using partial correlations (pr) analyses, controlling for age and sex. Results: RD was significantly correlated with 6MW performance (pr = −0.276, P = .04), T25FW (pr = −0.291, P = .03), and gait velocity (pr = −0.289, P = .03). AD was significantly correlated with 6MW performance (pr = −0.333, P = .01), T25FW (pr = −0.339, P = .01), and gait velocity (pr = −0.328, P = .01). FA was not sig-nificantly correlated with any of the walking parameters (P > .05). Conclusions: We provide novel evidence of possible motor path-way damage involved in walking performance in MS. There may be subtle differences in AD and RD associated with walking outcomes,

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Posters: Basic Science

PCR. Results: Relapsing MS patients had decreased expression of RGC-32 (P < .0001), FasL (P < .0005), and SIRT1 (P < .003) but no change in CDC2 compared to stable MS patients. Nonresponders to GA treatment were defined as patients who exhibited at least two relapse events following the initiation of GA treatment. Responders to GA treatment had significantly higher levels of RGC-32 (P < .0001), FasL (P < .003), and SIRT1 (P < .009) but no change in CDC2 com-pared to patients who were considered nonresponders. Receiver operating characteristic analysis was used to assess the predictive accuracy of each putative biomarker. Predictive probabilities for relapse were 90% using RGC-32, 84% using FasL, and 73% using SIRT1. Predictive probabilities for responsiveness to GA treatment were 85% using RGC-32, 85% using FasL, and 71% using SIRT1. Conclusions: The data suggest that RGC-32, FasL, and SIRT1 could serve as potential biomarkers for the prediction of MS relapses and the evaluation of patient response to GA therapy. Such information could help guide treatment decisions and improve MS patient out-comes.

Supported by: Teva Neuroscience, University of Maryland School of Medicine Office of Student Research, Foundation of the CMSCDisclosure: Adam M. Kruszewski, Cosmin A. Tegla, Cornelia Cudrici, Vingh Nguyen, Gautam K. Rao, Walter Royal III, Christopher T. Bever Jr., Violeta Rus: Nothing to disclose. Horea Rus: Teva Neuroscience (grant/research support).Keywords: Biomarkers in MS, Immunology and MS

(SC02) GAIT TERMINATION IN INDIVIDUALS WITH MULTIPLE SCLEROSISKathleen L. Roeing, Douglas A. Wajda, Robert W. Motl, Jacob J. Sosnoff

Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL

Background: Multiple sclerosis (MS) is a neurodegenerative dis-ease that commonly affects walking. Walking is typically examined during continuous tasks. Consequently, there is little knowledge regarding the impact of MS on essential components of walking, such as gait termination (GT). Objectives: The purpose of this investigation was to compare planned GT in individuals with MS and healthy controls during simple walking tasks and cognitively distracting tasks. We hypothesized that individuals with MS would have impairments in GT compared to age-matched controls, espe-cially during the cognitively challenging condition. Methods: Twenty-five individuals with MS (mean age 61.1 ± 8.4 years) and 30 age-matched controls (mean age 64.3 ± 5.3 years) participated. Participants completed four comfortable paced walking trials in which they terminated their walking at a prescribed location on a pressure-sensitive walkway. The first two trials consisted of simply walking, while the last two consisted of walking while engaged in a cognitive task. Maximum gait velocity for each trial was determined. GT performance was quantified with two approaches. First, a global measure of success or failure to stop reported as failure rate was computed. Second, the time to stop normalized to maximum walk-ing velocity was calculated for successful trials. A repeated-measures ANOVA was used to investigate group and task differences in gait velocity and termination time. Two-proportion Z-tests were utilized to compare failure rates as a function of group and task. Results: The MS group had a lower velocity (89.9 ± 33.3 cm/s) than the control group (142.8 ± 22.4 cm/s), and there was a significant reduction with the added cognitive task in both groups (MS: 73.9 ± 30.7 cm/s; control: 120.0 ± 25.9 cm/s). There was no difference in failure rates between groups: 21% (MS) vs. 16% (control). There was nearly a 10-fold increase in failure rates in both groups when performing the cognitive condition compared with baseline (3.6% vs. 33%). There was a group difference in GT time: 1.11 ± 1.03 (MS) vs. 0.47 ± 0.17 (control). Conclusions: Compared to controls, the MS group had a similar amount of GT failures despite walking at slower speeds. Although individuals with MS walked more slowly than age-matched controls, they required a greater amount of time to terminate their gait. Future research examining the clinical signifi-cance of GT is warranted.

found to have an MGM, and later developed tumefactive demyelin-ation (TD) following radiotherapy. A review of relevant literature will be provided. Methods: Case report and literature review. Results: A 54-year-old right-handed woman presented with painful right eye and blurry vision. She was diagnosed with right ON and treated with IV steroids with good response. Magnetic resonance imaging (MRI) showed an incidental right cavernous sinus MGM (separate from the optic nerve). Fractional radiotherapy was performed (total dose of 50.4 Gy). Overall, the patient improved and the size of her MGM remained stable. However, 30 months later, she presented with blurry vision, binocular diplopia, and gait imbalance. At that time, brain MRI showed numerous areas of abnormal FLAIR/T2 sig-nal, involving white-matter structures within the corona radiata, cen-trum semiovale, and subcortical regions. The largest area of abnor-mal signal was demonstrated in the right parieto-occipital region and measured 1.8 × 2.3 × 2.7 cm. T1 enhancement was evident in multiple lesions and incomplete ring enhancement was identified. Cerebrospinal fluid (CSF) analysis showed 6 unmatched oligoclonal bands, elevated immunoglobulin G synthesis rate, and unremarkable cytology. A diagnosis of TD was established, and the patient was treated with steroids. Review of the literature shows a few cases in which MS was triggered or worsened following brain radiotherapy. Also, experimental studies support the notion that brain radiation can have early and/or delayed adverse effects on brain tissue such as localized or disseminated demyelination and/or brain necrosis. Conclusions: Our patient represents an atypical case of quiescent MS that was unmasked later in life by localized disruption imposed by the brain MGM and/or brain radiotherapy. Further research is needed to look for similar associations and perhaps confirm such potential relationships.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Etiology of MS, Imaging and MS, Immunology and MS

BASIC SCIENCE

(SC01) RGC-32, FasL, AND SIRT1 AS POTENTIAL BIOMARKERS OF RELAPSE AND RESPONSE TO TREATMENT WITH GLATIRAMER ACETATE IN MULTIPLE SCLEROSISAdam M. Kruszewski,1 Cosmin A. Tegla,1,2 Cornelia Cudrici,1 Vingh Nguyen,3 Gautam K. Rao,1 Walter Royal III,1,4 Christopher T. Bever Jr.,1,2,4 Violeta Rus,3 Horea Rus1,2,4

1Department of Neurology, University of Maryland School of Medicine, Baltimore, MD; 2Research Service, Veterans Administration Maryland Health Care System, Baltimore, MD; 3Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine, Baltimore, MD; 4Veterans Administration Multiple Sclerosis Center of Excellence, Baltimore, MD

Background: Due to the heterogeneous nature of relapsing-remitting multiple sclerosis (RRMS), it is difficult to predict patient response to treatment. Currently there is a critical need for the devel-opment of reliable biomarkers to aid clinicians in the management of RRMS patients. Previously we have shown that the Response Gene to Complement (RGC)-32 is expressed by CD3+ as well as CD4+ T cells in peripheral blood mononuclear cells (PBMCs) and in brain tissue from RRMS patients. RGC-32 regulates cell cycle kinase CDC2 activ-ity. In turn, CDC2 modulates the expression of FasL and SIRT1, key regulators of T-cell survival. Previous, separate studies have shown that RGC-32, FasL, and SIRT1 mRNA expression is significantly lower within PBMCs of RRMS patients during relapses compared to remission. Objectives: Presently, for the first time we longitudi-nally investigated the combined roles of RGC-32, FasL, SIRT1, and CDC2 as possible biomarkers of relapse and predictors of response to glatiramer acetate (GA) treatment in RRMS patients. Methods: Over the course of 2 years, a cohort of 15 GA-treated RRMS patients was clinically monitored using the Expanded Disability Status Scale, and blood samples were collected at 0, 3, 6, 12, and 24 months. Target gene mRNA expression was measured in patients’ isolated PBMCs using two-step real-time quantitative reverse transcription

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Posters: Basic Science

ing ability and has been identified as having a relationship with functional level and disease progression. Objectives: Determine whether RNFL measurement correlates with T25FW and serves as a surrogate anatomical marker of functional decline in individuals with MS. Methods: This was a longitudinal study of 514 MS patients with a mean age of 48.0 ± 0.54 years. The sample consisted of 408 females and 106 males. Mean disease duration was 9.8 ± 0.26 years; 89% were on disease-modifying therapies. Each subject had OCT and T25FW measured at two time points, separated by 1 to 3 years. Results: Spearman rho correlation was used to look at the relationship between RNFL and T25FW at the two points. While both correlations proved significant (time 1: rho = −0.10, P = .02; time 2: rho = −0.12, P = .007), the magnitudes were very small. Further, the correlation between the changes in RNFL and changes in T25FW was not significant (r = −0.02, P = .69). These results indicate that RNFL and T25FW are only trivially correlated. Conclusions: Cur-rent study examined the relationship between RNFL and T25FW over a span of up to 3 years in a large cohort. A significant relationship was found, but the effect was very small. As functional decline in MS can happen at a slow rate, the study will be continued longitudinally.

Supported by: None

Disclosure: Nothing to disclose

Keywords: Comprehensive care and MS, Management of activities of daily living in MS, Retinal nerve fiber layer

(SC05) ROCKY MOUNTAIN MULTIPLE SCLEROSIS CENTER BIOREPOSITORY FOR THE STUDY OF NEUROIMMUNOLOGIC DISORDERCourtney Knapp,1 Enrique Alvarez,1 Teri Schreiner,1,2 Danielle Harlow,1 Augusto A. Miravalle,1 John Corboy1

1Neurology, University of Colorado, Aurora, CO; 2Neurology, Children’s Hospital Colorado, Aurora, CO

Background: One of the major obstacles to addressing the cause and cure of multiple sclerosis (MS) and related disorders is limited access to a large number of biological samples with associated clini-cal information. We have established the Rocky Mountain Multiple Sclerosis Center (RMMSC) Biorepository to support the longitudinal collection of blood, cerebrospinal fluid (CSF), urine, stool, and data from patients who have been diagnosed with MS or related neu-rologic disorders. Objectives: These valuable samples are stored on the Anschutz medical campus of the University of Colorado Denver and made available to our researchers and collaborators studying inflammatory diseases of the nervous system. A variety of scientific questions can be addressed, including: What is the etiology of MS? What are the cellular or soluble factors mediating disease pathogenesis? What is the mechanism of action of current and future therapeutics? Methods: Over a period of 20 years, up to 5000 subjects, ages 1 to 75, will be enrolled to create one of the most comprehensive repositories in the country. We will collect CSF samples with paired serum from adult patients undergoing lumbar puncture as standard of care at the University of Colorado and pedi-atric patients at Children’s Hospital Colorado. Results: Currently we have samples from 355 patients, including 241 CSF samples from patients with a variety of diagnoses: 121 with confirmed MS, 19 inflammatory controls, and 128 non-inflammatory controls. These samples have facilitated several primary ex vivo investigations into the cellular and soluble factors (biomarkers) mediating disease pathogenesis in MS. Ongoing studies include evaluation of B-cell and astrocyte interaction in MS propagation and investigation into the role of extracellular vesicles in the physiologic or pathologic MS dis-ease state. Conclusions: Through collaboration and innovation, we will use these samples in discovery of etiology of MS and biomarkers of disease pathogenesis so that effective strategies for intervention and cure may be sought. Request for collaboration may be directed to the Rocky Mountain Multiple Sclerosis Center.

Supported by: National Multiple Sclerosis Society (IL Lot 006)Disclosure: Kathleen L. Roeing, Douglas A. Wajda, Jacob J. Sosnoff: Nothing to disclose. Robert W. Motl: Biogen, Acorda (consulting fees, grant/research sup-port); EMD Serono (fees for non-CME services from commercial interests or their agents).Keywords: Mobility

(SC03) FALLS IN OLDER INDIVIDUALS WITH AND WITHOUT MULTIPLE SCLEROSISDouglas A. Wajda, Robert W. Motl, Jacob J. Sosnoff

Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL

Background: Individuals with MS tend to display a high incidence of falls. However, little is known about the influence of aging on the rates and circumstances surrounding falls in older individuals with MS compared to their age-matched counterparts. Further understand-ing of falls in this segment of the MS population has the potential to inform future fall-prevention recommendations. Objectives: The aim of this study was to investigate the occurrence and rate of falls in older individuals with MS and age-matched controls. Methods: 24 individuals with MS (age: 61.8 ± 8.8 years; EDSS: median [IQR] = 6.0 [4.5–6.5]; years since diagnosis: 18.5 ± 8.9) and 24 age-matched controls (age: 63.5 ± 4.8 years) participated in the investigation. Prospective falls data were obtained through partici-pant self-report over a 3-month period with monthly falls diaries. The diaries were mailed back to the laboratory in prepaid envelopes. Participants were instructed to note any time they experienced a fall, which was defined as unintentionally coming to rest on the ground or lower level. The total number of falls, fall rate per month, and recur-rence were noted for each participant. Group differences in propor-tion of fallers and recurrent fallers were analyzed with the chi-square test while comparisons of falls and fall rates were determined with Mann-Whitney U tests. Results: Overall, a total of 104 falls were recorded over the 3-month period, 97 by the MS group and 7 by the age-matched controls. The MS group also fell at a significantly higher rate, averaging 1.35 falls/month/person, compared to 0.10 falls/month/person for the control group (P < .001). The MS group con-tained significantly greater proportions of both fallers (75% vs. 17%, P < .001) and recurrent fallers (63% vs. 4%, P < .001) than the con-trol group. Conclusions: The findings suggest that fall incidences, rates, and recurrence in older adults with MS are significantly greater than in age-matched counterparts. Previous literature has primarily focused on falls in the younger segment of the MS population, and the current study serves to expand those observations. Ultimately, the prevalence of falling in older adults with MS highlights the impor-tance of designing high-quality fall-prevention programs and interven-tions for this subset of the MS community.

Supported by: National Multiple Sclerosis Society (IL Lot 006)Disclosure: Douglas A. Wajda, Jacob J. Sosnoff: Nothing to disclose. Robert W. Motl: Biogen, Acorda (consulting fees, grant/research support); EMD Serono (fees for non-CME services from commercial interests or their agents).Keywords: Falls and MS

(SC04) LONGITUDINAL STUDY OF TIMED 25-FOOT WALKS AND RETINAL NERVE FIBER LAYER IN A LARGE MULTIPLE SCLEROSIS COHORTCecilie Fjeldstad,1 Joseph P. Weir,2 Gabriel Pardo1

1MS Center of Excellence, OMRF, Oklahoma City, OK; 2Robinson Health and Physical Education Center, University of Kansas, Lawrence, KS

Background: Correlation of anatomical parameters with measure-ments of clinical function is needed in order to validate them as surrogate markers and establish practical implications for patient management in multiple sclerosis (MS). Measurement of the retinal nerve fiber layer (RNFL) by optical coherence tomography (OCT) is a reliable, noninvasive quantification of a neuronal compartment that correlates with brain volume loss as measured by magnetic resonance imaging (MRI). The Timed 25-Foot Walk (T25FW) is a simple bedside test that correlates well with other measures of walk-

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Posters: Technology

range of symptoms, including sleep problems, pain, and fatigue. In this study, we assessed the feasibility and acceptance of an electronic diary (ED) to help patients maintain a sleep/symptom diary. Objec-tives: To test feasibility and acceptability of electronic sleep and symptom diaries delivered using an e-mail message link to measure sleep and symptoms in patients with MS. Methods: A total of 34 consecutive subjects with MS were recruited from an MS clinic and the surrounding community. Inclusion criteria included knowledge of a computer, the Internet, and the English language. During the base-line visit, a set of questionnaires was administered to collect infor-mation about demographics and sleep. Then the participants were asked to use EDs daily over the course of 7 consecutive days, which was repeated 8 weeks later. The link to the ED was sent via REDCAP data capture program using a semistructured qualitative patient diary, as well as the SR-EDSS, a Sleep VAS, MS-Related Symptom Scale, and Sleep Behavior Checklist. A total of 28 participants com-pleted the EDs and were included in this analysis. Statistical analyses were performed using SAS version 9.4. Results: The majority (83%) of participants were female, the mean age was 42 years, and the mean SR-EDSS score was 3.7. Approximately 15% of participants had secondary progressive MS. Participants were highly compliant with diary completion over the entire 8 study weeks, with 82.3% of diaries completed. Submission rate did not differ across age, gender, or MS subtype. However, there was a trend toward submission dif-ference related to a higher education level. Participants found the methodology to be acceptable and felt comfortable participating in the study. Conclusions: Findings from this feasibility study provide preliminary evidence for the use of EDs for sleep and symptom data collection for patients living with MS. Tailoring this technology to patient needs and preferences may improve symptom management and communication in patients with MS.

Disclosure: Nothing to discloseKeywords: Management of activities of daily living in MS

(TC03) PREDISPOSITION AND MOTIVATION ASSESSMENT IN USING TECHNOLOGIES IN MULTIPLE SCLEROSIS: A QUESTIONNAIRE ON A WEARABLE TOOL FOR UNOBTRUSIVE MOTOR AND COGNITIVE MONITORINGAndrea Tacchino,1 Enrico d’Amico,2 Michela Ponzio,1 Sara Facchinetti,2 Giampaolo Brichetto,1 Maria Bulgheroni2

1Scientific Research Area, Italian MS Society, Genoa, Italy; 2R&D Department, Ab.Acus, Milan, Italy

Background: In recent years, technologies have been increasingly adopted both in daily activities and in clinical practice. Thus, the need to evaluate their use and disposition is becoming crucial, espe-cially for wearable systems created to improve quality of life in peo-ple with motor and cognitive deficits. Objectives: We assessed the predisposition and motivation of people with multiple sclerosis (MS) to use wearable systems able to detect early changes in motor and cognitive performance and to allow the monitoring of daily activities. Methods: The study is based on the Technology Acceptance Model (TAM), a standardized Likert questionnaire able to measure predispo-sition and motivation to use technologies. TAM particuarly evaluates the perceived usefulness and ease of use of technologies, referring to a specific selected system, verbally described before administration. We selected a wearable and unobtrusive system able to monitor motor and cognitive performance during daily activities and related well-being. This system, not yet realized, will allow the unobtrusive recording of behavioral information about the user, which will be sent daily and automatically to a personal tablet and/or smartphone for statistical analysis to detect possible significant changes indicat-ing a decline in performance. On the basis of the analysis, simple exercises will automatically be suggested in order to achieve a better status. We interviewed 28 people with MS (mean age 49.82 years; EDSS 0–8; disease course relapsing-remitting, secondary progres-sive, primary progressive). Results: Preliminary results on perceived usefulness showed that people with MS considered the selected sys-

Supported by: Rocky Mountain Multiple Sclerosis CenterDisclosure: Courtney Knapp, Teri Schreiner, Danielle Harlow, Augusto A. Miravalle, John Corboy: Nothing to disclose. Enrique Alvarez: Biogen Idec (con-sulting fees, grant/research support); Genzyme, Teva Neuroscience (consulting fees); Novartis (grant/research support).Keywords: Biorepository, Etiology of MS, Glial biology

TECHNOLOGY

(TC01) PROMOTING MULTIPLE SCLEROSIS MEDICATION ADHERENCE THROUGH TELEHEALTHJill R. Settle,1 Zipporah Miles,1 Heidi W. Maloni,1 McKenzie E. Bedra,2 Joseph Finkelstein,2 Mitchell T. Wallin1

1Washington DC VAMC, MS Center of Excellence, Washington, DC; 2Johns Hopkins University, Baltimore, MD

Background: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) have been available for more than 20 years; how-ever, adherence to a DMT regimen is often poor. The most common reason is forgetting to take medications on the specific day they are to be administered. The Home Automated Telehealth system has been successfully implemented in other chronic diseases including asthma, hypertension, and inflammatory bowel disease. Objec-tives: The primary aim of this study was to establish the feasibility of implementing a home telehealth program to support and monitor MS medication adherence without increasing health-care provider bur-den. Methods: We addressed the assessment of poor adherence using a comprehensive Home Automated Telemanagement system for MS (MS HAT). MS HAT is a home-based Internet module that sup-ports patient self-management, patient-provider communication, and patient education. For approximately 6 months, 30 participants were randomized to either MS HAT or treatment as usual. All participants stored their interferon beta-1a (IFNβ-1a) syringes in a clear syringe container and maintained a paper calendar of IFNβ-1a adherence. Pharmacy refill rates were also collected from medical records. Par-ticipants in the MS HAT condition received text or e-mail reminders to administer their medications. Results: There were no significant differences in demographic variables between the two groups. Like-wise, adherence did not significantly differ between the two groups. IFNβ-1a MS HAT alert rates were negatively correlated with syringe counts (r = 0.61, P = .026). As alerts decreased, syringes collected increased. Syringe count was positively related to change in Morisky score for IFNβ-1a (r = 0.60, P = .002). As self-reported adherence improved, the number of syringes collected also increased. Pharmacy refills of IFNβ-1a were directly related to calendar reports of taking IFNβ-1a (r = 0.52, P = .040) and syringe counts (r = 0.69, P < .001). As pharmacy refills increased, so did calendar reports and syringes collected. Conclusions: The strong correlations between self-report and objective measures of adherence suggest that self-reported monitoring through an automated telehealth mechanism, such as MS HAT, can provide a valid assessment of DMT adherence. Importantly, utilizing an automated electronic system reduces the time spent making phone calls and researching pharmacy refill records by health-care providers.

Supported by: Biogen IdecDisclosure: Jill R. Settle, Zipporah Miles, Heidi W. Maloni, McKenzie E. Bedra: Nothing to disclose. Joseph Finkelstein, Mitchell T. Wallin: Biogen Idec (grant/research support).Keywords: Comprehensive care and MS, Disease-modifying treatments in MS, Nursing management in MS

(TC02) THE USE OF ELECTRONIC SLEEP AND SYMPTOM DIARIES: A FEASIBILITY STUDYPamela K. Newland

Nursing, Barnes Jewish College, Goldfarb School of Nursing, St. Louis, MO

Background: Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system. Patients suffer from a wide

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Posters: Technology

of dimethyl fumarate (DMF) can reduce both the relapse of patients with MS and the formation of new white-matter lesions. However, the clinical utility of DMF can be impaired by poor retention in the CNS and by the complexity of its transport to the blood-brain barrier (BBB). Solid lipid nanoparticles (SLN) can selectively reach the brain and carry water-insoluble drugs, such as DMF. The intranasal route (IN) is considered an alternative that more efficiently allows the effect of drugs on the CNS, because the drug crosses the BBB and is not subjected to first-pass hepatic metabolism. Due to the activity of DMF in MS and in view of its low solubility in water, there is a need to develop a nanostructured carrier capable of overcoming the BBB and directing it to the CNS. This will allow better therapeutic efficiency, minimizing side effects and reducing the frequency of drug adminis-tration. Objectives: To develop SLN containing DMF and perform physicochemical characterization. Methods: The SLN was obtained by an ultrasonication method, and it was composed of surfactants (poloxamer 188 and soy lecithin), lipid (glycerylmonosterate), and water. Different formulations have been developed by the variation of the lipid contents, surfactants, and drug. The SLN were character-ized by light scattering (LS), zeta potential (ZP), scanning electronic microscopy (SEM), and atomic force microscopy (AFM). Results: The results showed that the diameter of SLN decreased as surfactant concentration increased. On the other hand, the diameter increased as both lipid and drug contents in the formulation increased. The diameters of DMF-loaded SLN and DMF-unloaded SLN were about 327 and 287 nm, respectively. The ZP was negative in all formula-tions. By the AFM and SEM images it was possible to identify the morphology of SLN, which showed elongated and spherical par-ticles. The AFM and SEM images confirmed the LS results of the SLN diameter. Conclusions: The SLN described in this study have physico-chemical characteristics that enable them to be used as a car-rier for the nasal administration of DMF.

Supported by: FAPESP, CNPQDisclosure: Nothing to discloseKeywords: Complementary/alternative therapies in MS, Dimethyl fumarate and MS, Disease-modifying treatments in MS

(TC06) USING TELEHEALTH AND DATABASES TO EXPAND MULTIPLE SCLEROSIS SPECIALTY CARE IN THE VA HEALTH-CARE SYSTEMHeidi W. Maloni, Jill R. Settle, Akimyo C. Russell, Mitchell T. Wallin

Washington, DC VAMC, MS Center of Excellence, Washington, DC

Background: Because of the shortage of subspecialty multiple scle-rosis (MS) clinics in the VA health-care system, patients often travel great distances to access specialty care. Compounding this, disabil-ity, cost, awareness of the availability of specialty clinics, and obtain-ing accessible transportation remain barriers to treatment. Clinical Video Telehealth (CVT) provides a mechanism by which veterans can receive care from specialty clinics without incurring the burden of traveling to distant medical centers. The Integrated Neurology Project was launched in 2014 to expand the reach of specialty neurologic care, focusing on Parkinson disease, epilepsy, and MS. Objectives: In relation to MS, the primary aim of this project was to identify all active patients with MS in VISN 5 (Veteran Integrated Service Net-work) and expand access to care through the CVT system, electronic consults, and traditional face-to-face care. The secondary aim of the project was to enter patients with MS in a national MS surveillance registry using the MS Assessment Tool (MSAT). Methods: Coordina-tion with outlying medical centers and clinics without a specialty-care clinic was established. Veterans who had been assigned ICD-9 code 340.0 between 2011 and 2013 were identified and captured using the Computerized Patient Record System. These patients were contacted by a nurse from an MS specialty clinic and offered par-ticipation in the CVT program. CVT establishes a secure audio and video link between patients and providers. Using this system, MS specialty providers conducted outreach to outlying medical centers,

tem useful (75%) and able to improve their activities (79%), although they reported a lower intention to use again (61%). This discrepancy could be due to the lack of a prototype. 57% of the sample showed an affinity for technologies (70%). Therefore, the system is considered easy-to-use, fully usable (68%), and agreeable (64%). The use of technologies is favored by a preexisting familiarity. Relationship to age and disease course is still under investigation. Conclusions: Results showed a positive predisposition to the system, important both as a starting point for design and development and because it took into account final users’ point of view. The TAM will be adopted during the testing phase in order to assess whether actual use might modify initial perceptions.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Complementary/alternative therapies in MS

(TC04) COMPARING THE EFFECTS OF WHOLE-BODY VIBRATION TO STANDARD EXERCISE IN AMBULATORY PEOPLE WITH MULTIPLE SCLEROSIS: A RANDOMIZED CONTROLLED FEASIBILITY STUDYMarcin K. Uszynski,1 Helen Purtill,2 Alan Donnelly,3 Susan B. Coote1

1Department of Clinical Therapies, University of Limerick, Limerick, Ireland; 2Department of Mathematics and Statistics, University of Limerick, Limerick, Ireland; 3Physical Education and Sport Sciences Department, University of Limerick, Limerick, Ireland

Background: Whole-body vibration (WBV) is a technology that has potential benefits in both healthy and neurologic populations. It is currently unknown whether WBV is equivalent or superior to standard exercise in people with multiple sclerosis (MS). Objec-tives: This study aimed first to investigate the feasibility of the study protocol and outcome measures, second to obtain data in order to inform the power calculations for a larger randomized controlled trial (RCT), and finally to investigate whether WBV is more effective than the same duration and intensity of standard exercises (EXE) in people with MS. Methods: Twenty-seven people with MS (mean [SD] age, 48.1 [11.2] years) with minimal gait impairments were ran-domly allocated to WBV (n = 14) or EXE (n = 13). Participants were measured before and after 12 weeks of intervention with isokinetic muscle strength, vibration threshold, Timed Up and Go test (TUG), Mini-BESTest (MBT), 6-Minute Walk test (6MW), Multiple Sclerosis Impact Scale-29 (MSIS-29), Modified Fatigue Impact Scale (MFIS), and Verbal Analogue Scale for sensation (VAS). Results: WBV intervention was found feasible, with a low dropout rate (11.1%) and high compliance (90%). Data suggest that a sample of 52 in each group would be sufficient to detect a moderate effect size, with 80% power and 5% significance for the 6MW. Large effect sizes in favor of standard exercise were found for vibration threshold at the fifth metatarsophalangeal joint and heel (P = .014, r = 0.5 and P = .005, r = 0.56, respectively). Although improvements were found within groups after interventions for muscle strength, balance, or gait, no between-group differences were found for those outcome measures (P > .05). Conclusions: Our data suggest that the protocol is feasible, and there were no adverse effects. Future studies should be powered to detect a change in walking endurance. Although WBV is not more effective than exercise, it may offer similar improvements to exercise.

Supported by: Irish Research CouncilDisclosure: Nothing to discloseKeywords: Comprehensive care and MS

(TC05) PHYSICOCHEMICAL CHARACTERIZATION OF SOLID LIPID NANOPARTICLES FOR DIMETHYL FUMARATE RELEASEGisela Bevilacqua Rolfsen Ferreira da Silva,1 Anselmo Gomes de Oliveira,2 Fabio de Lima Leite1

1UFSCAR, Sorocaba, Brazil; 2UNESP, Araraquara, Brazil

Background: Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease that produces neuroinflammation and demy-elination in the central nervous system (CNS). Oral administration

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Posters: Disease Management, Mechanisms, and Treatment

>18 participants. Feedback from the first 12-week series led to an increased emphasis on case-based education in the second 12-week series. Recruitment was most successful among community neurolo-gists, although primary-care providers who participated valued the case consultation, learning about resources, and addressing complex MS care issues through a comprehensive model. Conclusions: MS Project ECHO was successfully delivered to enhance the knowledge of community providers treating individuals with MS. Replication of this model and long-term follow-up are needed to determine whether this model can be applied more broadly to improve the quality of MS care and outcomes for underserved MS populations.

Supported by: Medtronic Foundation–Patient Link ProgramDisclosure: Gary Stobbe, Deborah Hertz, George H. Kraft, Annette Wundes, Kent Unruh, Piper Reynolds, Rosalind C. Kalb, Meghan Beier, Katharine Alexander, John D. Scott, Kurt Johnson: Nothing to disclose. Kevin Alschuler: Consortium of Multiple Sclerosis Centers, National Multiple Sclerosis Society, National Institute on Disability and Rehabilitation Research, PCORI (grant/research support).Keywords: Comprehensive care and MS, Innovative telehealth pilot

DISEASE MANAGEMENT, MECHANISMS, AND TREATMENT

(DX07) LYMPHOCYTE COUNTS AFTER INITIATION OF DIMETHYL FUMARATEYaser Almalik,1 Jamie Greenfield,1 Winona Wall,1,2 Luanne M. Metz1

1Clinical Neurosciences, University of Calgary, Calgary, AB, Canada; 2University of Calgary, Calgary, AB, Canada

Background: Dimethyl fumarate (DMF) is a first-line oral therapy for relapsing-remitting multiple sclerosis (RRMS), but prolonged lymphopenia may jeopardize safety. Objectives: This retrospec-tive cohort study aims to determine lymphocyte count change after initiation of DMF in a real-world clinical setting. Methods: Data from patients with RRMS who initiated DMF between July 1, 2013, and December 31, 2014, were analyzed. The Calgary MS Clinic has managed over 2500 disease-modifying therapy (DMT) patients; administrative processes, electronic medical records (EMRs), and a database ensure that use is tracked. A checklist is used to support patient education and safety prior to starting DMT. Demographic, clinical, and laboratory information were collected from patient EMRs and the clinic database. Results: This analysis included 170 patients. At treatment initiation mean age was 42.1 years, 75% were women, mean disease duration was 12.5 years, median EDSS was 2, and 24% were treatment naïve. Median follow-up time to Decem-ber 31, 2014, was 6.4 months (range, 1.5–17.7). DMF was dis-continued by 17 patients (10%); median time to discontinuation was 3.1 months (range, 0.6–12.4). Mean lymphocyte count at baseline was 2.0 × 109 cells/L (range, 0.5–4.4). Among 84 (49%) patients followed for 6 months, only 61 (73%) had a 6-month blood test for safety monitoring; mean lymphocyte count was 1.4 × 109 cells/L (range, 0.4–2.6). Lymphocyte counts decreased in 55 (90%) patients from baseline to 6 months with a mean absolute change of −0.72 × 109 cells/L (range, −2.8 to +0.8) and a mean percent change of −32% (range, −74% to +50%). Lymphopenia (lymphocyte count < 0.5) occurred at least once during follow-up in 5 patients (3%); this was the most recent lab test in some patients, and in other patients it was transient. No patient discontinued DMF as of December 31, 2014, due to lymphopenia. Conclusions: The Canadian prod-uct monograph for DMF indicates that the lymphocyte count will decrease by 30% within the first year and lymphopenia will occur in less than 6%; these data are consistent with this expectation. Howev-er, improved patient adherence to lab monitoring is needed, as lym-phopenia is very likely to be missed when such a large proportion of patients (27% at this time point) fail to comply with safety monitoring. Adherence to lymphocyte monitoring, and lymphocyte results, over the first year of treatment will be presented.

community-based outpatient clinics, and individual veterans in their homes. Concurrently with each visit, the MSAT was completed, which both populated the national MS registry with core data and estab-lished a baseline for care. Veterans who established care within the specialty clinic were then seen by a neurology provider from the MS Centers of Excellence. Results: From the initiation of the project in January 2014 to the end of the project in January 2015, 442 veter-ans with MS were identified in VISN 5. Twelve percent had not previ-ously been seen by an MS specialty-care clinic. By establishing these patients at the DC or Baltimore medical centers, a total of $673,002 was recovered. Additionally, 61 veterans chose to connect with the MS specialty clinic via the CVT system. This saved a total of $30,500 in travel costs for the VHA. During the project, 154 veterans were assessed using the MSAT. Conclusions: Patients who established care with MS specialty clinics using the CVT system have been able to connect with MS specialty providers as well as access important resources. An additional benefit was that use of CVT represented cost savings to the institution as well as decreased burden to the vet-eran. Telehealth and the MS Surveillance Registry are important tools to optimize MS access and management.

Supported by: Biogen IdecDisclosure: Heidi W. Maloni, Jill R. Settle, Akimyo C. Russell: Nothing to dis-close. Mitchell T. Wallin: Biogen Idec (grant/research support).Keywords: Comprehensive care and MS, Economic issues and MS, Equipment in MS

(TC07) MS ECHO: INNOVATIVE PILOT TO IMPROVE THE CAPACITY OF PROVIDERS IN UNDERSERVED AREAS TO TREAT MULTIPLE SCLEROSISGary Stobbe,1 Deborah Hertz,2 George H. Kraft,3 Kevin Alschuler,3 Annette Wundes,1,3 Kent Unruh,4 Piper Reynolds,2 Rosalind C. Kalb,2 Meghan Beier,3 Katharine Alexander,3 John D. Scott,4 Kurt Johnson3

1Neurology, University of Washington, Seattle, WA; 2National Multiple Sclerosis Society, New York, NY; 3Rehabilitation Medicine, University of Washington, Seattle, WA; 4University of Washington, Seattle, WA

Background: MS Project ECHO (Extension for Community Health-care Outcomes) is a collaborative effort between the University of Washington (UW) and the National Multiple Sclerosis Society (Soci-ety) to improve MS care in underserved communities. The model catalyzes a mentor-based learning community where a multidisci-plinary specialty MS care team, primary-care providers, and com-munity neurologists engage through weekly videoconferencing and case-based learning with CME credits. The Project ECHO model has demonstrated improved health-care outcomes in pain management, hepatitis C, HIV, and other diseases. The pilot goal is to develop a Project ECHO for MS care and to establish feasibility and replicabil-ity. A unique characteristic of this ECHO is the collaboration between an academic center and a voluntary health organization. A grant to the Society from the Medtronic Foundation–Patient Link Program provided funds for this pilot. Objectives: 1) Develop an MS-focused curriculum, 2) identify recruitment strategies and assess retention among participants, 3) obtain meaningful feedback on satisfaction with the program, and 4) identify preliminary information to deter-mine impact on clinical care. Methods: A team consisting of repre-sentatives from the Society and the UW developed a curriculum and supporting resources to be tested during a 12-week series of 1-hour videoconference sessions with community neurologists and primary-care providers from Alaska, Idaho, Montana, and Washington. Each session included a brief didactic presentation and case presentations as well as introduction to resources available through the Society to support care delivery. Semistructured interviews and surveys were utilized to assess satisfaction. After the first 12-week series, the pro-gram was assessed and modifications made for a second 12-week series. Recruitment strategies targeted health-care providers from the Society’s resource database, the UW network, and the Health Resources and Services Administration (HRSA) list of rural providers. Results: Outcomes included developing a unique MS-focused curric-ulum and piloting the ECHO methodology in two 12-week series with

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Background: Natalizumab (NAT) is a monoclonal antibody that prevents entry of leukocytes into the CNS. This mechanism of action has made it one of the most effective therapies against multiple scle-rosis (MS). However, NAT’s use is limited by its risk of progressive multifocal leukoencephalopathy (PML). Moreover, switching from NAT to another therapeutic agent is made even more complex, as there is an increased risk of rebound inflammation. Dimethyl fuma-rate (DMF) is a new oral agent that offers a therapeutic alternative to patients stopping NAT. However, the safety and efficacy of this switch have not yet been studied. Objectives: To assess the stabil-ity of patients switched from NAT to DMF. A secondary objective is to search for factors that may predict stability on DMF. Methods: A telephone survey and chart review were done for 66 relapsing-remitting MS (RRMS) patients who had been switched from NAT to DMF. Factors analyzed included age, gender, duration on NAT, duration between NAT and DMF, and duration on DMF. Results: A total of 66 patients were surveyed; 47 (71.22%) remained stable when switched to DMF and 19 (28.78%) were found to be unstable on DMF. While the findings were not significant, the following trends were noticed. Female patients were 2.9 times more likely to be unstable compared to males. Patients under 60 years of age were 1.8 times more likely to be unstable compared to patients over 60 years of age. Patients on NAT for less than 2 years are 2.4 times more likely to be unstable compared to patients on NAT for more than 2 years. Patients who have an 8-week or less gap between NAT and DMF are just as likely to develop instability compared to patients with more than an 8-week gap between treatments. Patients who are on DMF for less than 6 months are 0.6 times less likely to be unstable than patients on DMF for longer than 6 months. In other words, patients on DMF for longer than 6 months are 1.7 times more likely to be unstable. Conclusions: A majority of patients remain stable when switching from NAT to DMF. Factors such as sex, age, and duration of NAT treatment may predict the probability of a successful transition. An extension of this study will be carried out that will look at MRI changes and relapse rate after a patient has stopped NAT and switched to DMF.

Supported by: NoneDisclosure: Faria S. Amjad: Teva (speaking honoraria). Nasima Afsari: Nothing to disclose. Carlo Tornatore: Biogen Idec (fees for non-CME services from com-mercial interests or their agents); Biogen Idec, Genzyme, Novartis (consulting fees).Keywords: Disease-modifying treatments in MS, Imaging and MS, Natural his-tory of MS

(DX10) ASSESSING THE INCIDENCE OF ELEVATION IN EOSINOPHILS WITH THE USE OF DIMETHYL FUMARATE IN MULTIPLE SCLEROSISStephen Aradi, Robert J. Soares, Derrick Robertson, Chetan Gandhy, Michelle Lyman

Neurology, USF Health Morsani College of Medicine, Tampa, FL

Background: Dimethyl fumarate (DMF) is an oral medication approved for the treatment of multiple sclerosis (MS). In the pivotal MS studies involving DMF, a transient increase in mean eosinophils were seen during the first 2 months of therapy. However, the inci-dence of this increase has not been reported. Objectives: To assess incidence of elevation in eosinophils with the use of DMF in multiple sclerosis. Methods: A retrospective chart review was conducted of all patients seen in our MS clinic from March 2013 through March 2014. The review focused on patients who were prescribed DMF under routine clinical care and had available pre- and post-dosing complete blood counts (CBCs), which included levels of eosinophils. Elevation in eosinophils in our chart review was defined as elevation above 7% of all leukocytes on differential. Results: A total of 191 patients started on DMF. A pre-dosing CBC was completed in 91.1% of patients and was obtained, on average, 10.9 weeks prior to start-ing DMF. A post-dosing CBC was completed in 77.5% of patients and was obtained, on average, 17.6 weeks after starting DMF. The incidence of elevation in eosinophils among patients who had post-

Supported by: NoneDisclosure: Nothing to discloseKeywords: Dimethyl fumarate, Disease-modifying treatments in MS, Manage-ment of activities of daily living in MS

(DX08) EXPANDING ANTIGEN-SPECIFIC T-REGULATORY TYPE 1 CD4+ T CELLS IN VIVO TO TREAT CNS AUTOIMMUNITYPoornima Ambalavanan

Microbiology, Immunology and Infectious Disease, University of Calgary, Calgary, AB, Canada

Background: T-regulatory cells hold promise as targets for therapeutic intervention in autoimmunity, but approaches capable of expanding antigen-specific T-regulatory cells in vivo do not currently exist. We have discovered that systemic delivery of nanoparticles (NPs) coated with type 1 diabetes–relevant peptide-major-histocom-patibility-complex (pMHC) class-II molecules triggers the formation and profound expansion of cognate T-regulatory-type-1 (TR1) CD4+ T cells in vivo, including mice humanized with lymphocytes from patients, leading to resolution of pancreatic islet inflammation and restoration of normoglycemia in spontaneously diabetic mice. Here, we show that treatment of MOG- or PLP-immunized B6 and HLA-DR4-IE transgenic C57BL/6.Iabnull mice with nanoparticles coated with disease-relevant pMHC class II molecules induces a systemic expan-sion and recruitment of cognate TR1 CD4+ T cells to the CNS, blunt-ing disease progression and restoration of motor function in paralytic mice. Objectives: To demonstrate that the autoimmune process in experimental autoimmune encephalomyelitis (EAE) generates autore-active memory-like CD4+ T cells with regulatory function that can be expanded by treating EAE mice with pMHC class II–coated NPs, thus affording therapeutic protection against cognate and noncognate effector T cells. Methods: EAE-relevant-pMHC class II complexes were expressed in lentivirus transduced CHO cells. Proteins secreted in the supernatant were purified using nickel columns and were directly coated on iron oxide NPs or were biotinylated to produce pMHC tetramers. EAE-induced mice were treated with pMHC-coated NPs, twice a week, for 5 weeks and disease scores were monitored regularly. At 5 weeks, cognate expansion of autoregulatory CD4+ T cells and reduced inflammation, induced by NP therapy, was checked by flow cytometric analyses of pMHC class II tetramer+ cells and different histologic staining, respectively. Results: pMHC-NP therapy was able to both blunt disease progression when given at the onset of disease and restore motor function in paralytic mice when given at the peak of disease. These therapeutic effects were mirrored by weight gain, and were associated with systemic expansion of cognate TR1 CD4+ T cells, significant reductions in macrophage/microglial infiltration in the cerebellum, decreased number of inflammatory foci and areas of demyelination in the cer-ebellum’s white matter, and decreased demyelination of the spine. Conclusions: These nanomedicines promote the differentiation of disease-primed autoreactive T cells into TR1 cells, which in turn sup-press autoantigen-loaded antigen-presenting cells, blunting disease progression, without compromising systemic immunity. pMHC class II–based nanomedicines thus represent a new class of drugs poten-tially useful for treating a broad spectrum of autoimmune phenomena in a disease-specific manner.

Supported by: Supervisor’s grantDisclosure: Nothing to discloseKeywords: CNS repair, Disease-modifying treatments in MS, Immunology and MS

(DX09) THE SAFETY AND EFFICACY OF SWITCHING FROM NATALIZUMAB TO DIMETHYL FUMARATE: REAL-WORLD EXPERIENCEFaria S. Amjad, Nasima Afsari, Carlo Tornatore

Neurology, Medstar Georgetown University Hospital, Washington DC

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Supported by: Genzyme, a Sanofi company; Bayer HealthCare PharmaceuticalsDisclosure: Ann D. Bass: Acorda, Biogen, Mallinckrodt, Novartis, Sanofi-Gen-zyme, Teva Neuroscience (consulting fees, speakers’ bureau, honorarium); Biogen, Merck Serono, Novartis, Sanofi-Genzyme, Teva Neuroscience, Roche-Genentech (grant/research support). Keith R. Edwards: Actelion, Biogen Idec, Eisai, Eli Lilly, Genentech, Genzyme, Novartis, TauRx Therapeutics, Vaccinex (grant/research support); Biogen Idec, Genzyme, Novartis (consulting fees). Per S. Sørensen: Biogen Idec, Merck Serono, Novartis, Genzyme, Teva Pharmaceutical Industries Ltd., GlaxoSmithKline (advisory boards); Biogen Idec, Merck Serono, Teva Pharmaceutical Industries Ltd., Genzyme, Novartis (consulting fees). Krzysztof W. Selmaj: Biogen Idec, Inc (fees for non-CME services from commercial interests or their agents); Genzyme, Novartis, Ono, Roche, Synthon, Teva (consulting fees). David H. Margolin: Genzyme, a Sanofi company (salary). Linda Kasten: Genzyme, a Sanofi company (consulting fees). Edward J. Fox: Bayer HealthCare, Biogen Idec, Eli Lilly, EMD Serono, Genzyme, Novartis, Ono, Opexa Therapeu-tics, Pfizer, Sanofi, Teva (consulting fees, grant/research support, honoraria, travel support).Keywords: Alemtuzumab, Disease-modifying treatments in MS

(DX12) THE EFFECTS OF BODY-MASS INDEX ON MULTIPLE SCLEROSIS PROGRESSIONAliza Ben-Zacharia

The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai School of Medicine, New York, NY

Background: Multiple sclerosis (MS) is a progressive neurologic disease leading to loss of function and disability. MS and obesity are both considered inflammatory diseases, and they might be linked through pathophysiological processes. The relationship between body-mass index (BMI) and MS progression is unknown. Objec-tives: To evaluate the relationship between BMI and MS progres-sion as measured by the Expanded Disability Status Scale (EDSS), magnetic resonance imaging (MRI) new lesions, relapse rate, and the Timed 25-Foot Walk (T25FW). Methods: Subjects were identified through age, gender, race, disease duration, smoking, and MS type from an MS center in New York City and followed retrospectively for 5 years. Logistic regression analysis was performed to determine the association between the baseline BMI and MS progression: dis-ability, new MRI lesions, relapse rate, and the average T25FW (n = 150). Results: The mean age was 45.5 years (SD 14.3), 79% were females, and 59% were non-Hispanic whites; 68% were never smok-ers, and 77% had relapsing-remitting MS (RRMS). The mean BMI was 27, with 40 (27%) being classified as overweight and 46 (30%) as obese. 63 (42%) developed disability, 70 (47%) had increased brain MRI lesions, and 42 (28%) had increased spine MRI lesions; 110 (73%) had increased relapses by at least one relapse during the 5 years, and 38 (25%) had a 20% increase on the T25FW. The odds of having increased EDSS by at least 1 point in obese patients with mild disability was 8 times greater than those with normal BMI (P = .017) controlling for age, gender, race/ethnicity, smoking his-tory, disease duration, brain changes, number of relapses, and MS type. The odds of having new brain MRI lesions was 6.2 times great-er in overweight subjects (P < .0001) and 2.6 times greater in obese subjects (P = .048) than in subjects with normal BMI controlling for age, gender, EDSS, number of relapses, and disease duration. The odds of having at least one relapse in 5 years was 3.8 times (P = .040) greater in obese subjects than in nonobese subjects controlling for gender and smoking history. The odds of having a 20% change on the T25FW were 1.1 (P = .047) times for each increase of one unit of the baseline BMI controlling for age, gender, and disease duration. Non-Hispanic blacks had 5 times greater odds of having high disability (P = .015) than non-Hispanic whites controlling for age and duration of disease, and current smokers had 5 times great-er odds of having increased disability than never smokers (P = .03). Conclusions: BMI may have an important role in MS outcomes. Assessment and addressing a plan of care with dietary guidelines and weight control programs for patients with MS may aid in mini-mizing the progression of the disease and other chronic illnesses such as cardiovascular diseases and diabetes.

dosing CBCs was 8.1%. Conclusions: To our knowledge, this is the first study assessing incidence of elevations in eosinophils with the use of DMF in MS. There are several potential clinical implications of these data. First, it has been postulated that DMF-related gastroin-testinal symptoms could be due to an eosinophilic gastroenteritis-like syndrome. Second, a transient increase in eosinophils has been observed with fumaric-acid esters, a similar compound to DMF used in psoriasis. This was attributed to elevations in IL-4 that stimulate eotaxin, an eosinophil-activating cytokine. DMF has also been shown to elevate IL-10, which along with IL-4 decreases Th1 cells and increases Th2 cells. Given that Th2 activation would be beneficial in MS, this increase in eosinophils might imply a positive treatment response and thus could be considered a biomarker. Further studies are indicated to investigate this.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Dimethyl fumarate in MS, Disease-modifying treatments in MS, Immunology and MS

(DX11) LYMPHOCYTE PHARMACODYNAMICS AND SAFETY OF NATALIZUMAB IN PATIENTS PREVIOUSLY TREATED WITH ALEMTUZUMABAnn D. Bass,1 Keith R. Edwards,2 Per S. Sørensen,3 Krzysztof W. Selmaj,4 David H. Margolin,5 Linda Kasten,6 Edward J. Fox7

1Neurology Center of San Antonio, San Antonio, TX; 2Multiple Sclerosis Center of Northeastern New York, Latham, NY; 3Danish Multiple Sclerosis Center, Rigshospitalet, Copenhagen, Denmark; 4Medical University of Lodz, Lodz, Poland; 5Genzyme, a Sanofi company, Cambridge, MA; 6PROMETRIKA, LLC, Cambridge, MA; 7Multiple Sclerosis Clinic of Central Texas, University of Texas Medical Branch, Austin, TX

Background: Alemtuzumab had superior efficacy compared with subcutaneous interferon beta-1a (SC IFNβ-1a), with manageable safety, during phase 2 and 3 studies of patients with relapsing-remitting multiple sclerosis (RRMS). Although patients and physicians may want to use other disease-modifying therapies (DMTs) after alemtuzumab treatment depending on individual patient profile, few data exist on the safety of this practice and effects on the immune sys-tem. Objectives: To examine lymphocyte pharmacodynamics and safety in patients treated with natalizumab after receiving alemtu-zumab in the alemtuzumab clinical development program for RRMS. Methods: In phase 2 (CAMMS223; NCT00050778) and phase 3 (CARE-MS I [NCT00530348] and CARE-MS II [NCT00548405]) studies, patients with active RRMS who were either treatment-naive or had an inadequate efficacy response to prior DMT (≥1 relapse after ≥6 months of treatment) received alemtuzumab 12 or 24 mg/day intravenously on 5 consecutive days at baseline and on 3 consecu-tive days 12 months later, or SC IFNβ-1a 3 times/week. In an ongo-ing extension study (NCT00930553), retreatment with alemtuzumab 12 mg, or treatment with other DMTs including natalizumab, was permitted. Patients who received SC IFNβ-1a in the CARE-MS studies could receive alemtuzumab 12 mg in the extension plus other DMTs. Lymphocyte counts were measured every 3 or 6 months and in the month following each alemtuzumab treatment course. Results: 10 patients received natalizumab after alemtuzumab (CAMMS223: n = 2; CARE-MS I: n = 1; CARE-MS II: n = 7); 9 had received two cours-es of alemtuzumab (24 mg: n = 4; 12 mg: n = 5), and 1 received SC IFNβ-1a in the core study and one course of alemtuzumab 12 mg in the extension. Mean (SD) time of natalizumab initiation was 2.03 (0.77) years after the last alemtuzumab dose; mean (SD) follow-up time after natalizumab initiation was 1.38 (0.71) years. CD4+ and CD8+ T-cell counts and CD19+ B-cell counts rose after the last dose of alemtuzumab, and rose further after natalizumab initiation. No adverse event (AE) types predominated during natalizumab treat-ment. One serious AE was reported in one patient during natali-zumab treatment (influenza). Conclusions: Lymphocyte counts after switching from alemtuzumab to natalizumab were consistent with the known pharmacodynamic effects of each drug. No unexpected AEs were observed with natalizumab.

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demonstrated significant clinical and magnetic resonance imaging (MRI) benefits versus placebo in patients with relapsing forms of mul-tiple sclerosis (RMS). Objectives: To characterize the early treatment effect of IFNβ-1a 44 µg SC tiw at 1 year in preselected subgroups of patients with RMS from the PRISMS study. Methods: This post hoc subgroup analysis assessed the treatment effect of IFNβ-1a 44 µg SC tiw versus placebo over 1 year in patient subgroups, stratified by baseline: 1) Expanded Disability Status Scale (EDSS) ≤ and >2.5 (median value); 2) relapses (prior 2 years) of < and ≥3; and 3) bur-den of disease (BOD; total T2 lesion area) of ≤ and >1992.5 mm2 (median value), as well as other characteristics (age, sex, and time since onset of MS). Relapse and MRI endpoints assessed included annualized relapse rate (ARR), time to first relapse, proportion of patients relapse-free, and number of active T2 lesions/patient/scan. Relative treatment effects of IFNβ-1a 44 µg SC tiw versus placebo were examined using rate ratios, hazard ratios, and odds ratios. Results: In PRISMS-2, patients were randomized to IFNβ-1a 44 µg (n = 184) or 22 µg (n = 189) SC tiw, or placebo (n = 187). In all subgroups examined, point estimates and 95% confidence inter-vals indicated IFNβ-1a 44 µg SC tiw reduced ARR versus placebo, consistent with the overall population; rate ratios ranged from 0.46 (0.32–0.66) among patients with <4 years since MS onset (n = 149) to 0.71 (0.55–0.92) among patients with baseline EDSS ≤2.5 (n = 221). All estimates of relative treatment effects favored IFNβ-1a 44 µg SC tiw over placebo on additional relapse endpoints in all baseline EDSS, relapse, and BOD subgroups investigated at 1 year. In analysis of active T2 lesions, rate ratios favored IFNβ-1a 44 µg SC tiw over placebo in all subgroups examined, ranging from 0.22 (0.14–0.33) in patients with <4 years since MS onset (n = 147) to 0.38 (0.27–0.53) in patients with ≥4 years since MS onset (n = 219). Conclusions: Subgroup analyses were consistent with find-ings in the overall population, demonstrating the treatment benefit of IFNβ-1a 44 µg SC tiw on relapse and MRI endpoints at 1 year in patients with RMS.

Supported by: EMD Serono (a subsidiary of Merck KGaA), Pfizer IncDisclosure: Mark Cascione: Acorda, Bayer HealthCare, Biogen Idec, EMD Serono, Genentech, Genzyme/Sanofi, Novartis, Pfizer, Roche, Teva (consulting fees, grant/research support, speakers’ bureau). Fernando Dangond, Juanzhi Fang: EMD Serono, Inc, a subsidiary of Merck KGaA (salary). Aaron Miller: Acorda, Biogen Idec, CVS Caremark, EMD Serono, Genzyme/Sanofi-Aventis, Glaxo-SmithKline, Novartis, Nuron Biotech Inc, Ono, Questcor (advisory board, con-sulting fees); Acorda, Biogen Idec, Genentech, Genzyme/Sanofi-Aventis, Questcor, Roche (grant/research support).Keywords: Disease-modifying treatments in MS, Imaging and MS, Interferon beta

(DX15) DISEASE-MODIFYING THERAPY AND THE DECISION-MAKING PROCESS FOR MULTIPLE SCLEROSIS PATIENTS IN NARCOMSStacey S. Cofield,1 Tuula Tyry,1 Nina Thomas,2 Sandre McNeal,1 Robert J. Fox,3 Ruth Ann Marrie,4 Gary Cutter1

1Biostatistics, University of Alabama at Birmingham, Birmingham, AL; 2Genentech, Inc, South San Francisco, CA; 3Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH; 4University of Manitoba, Winnipeg, MB, Canada

Background: Reasons for choosing/changing multiple sclerosis (MS) disease-modifying therapies (DMTs) may involve disease changes, financial considerations, or other factors. These decisions may be made by the patient, doctor, or both. With new DMTs emerg-ing, switching DMTs will become more complex, and it is important to understand who makes the decision, how, and why. Objectives: Describe the DMT status and changes to DMTs (eg, switch, discon-tinuation) in NARCOMS participants and how the decision is made by the patient and doctor. Methods: In fall 2014, participants provided DMT status (Yes/No), changes to DMT use (Yes/No), and control preference, defined as “the degree of control an individual wants to assume when decisions are being made about medical treatment.” The Control Preference Scale (CPS) consists of five images that show different patient/doctor roles in treatment decision-making

Supported by: NoneDisclosure: Teva, Novartis, Biogen Idec, Bayer, Questcor, Genzyme (consulting fees)Keywords: Complementary/alternative therapies in MS, Management of activi-ties of daily living in MS

(DX13) DISEASE ACTIVITY IN THE FIRST YEAR PREDICTS CLINICAL OUTCOMES IN PATIENTS WITH MULTIPLE SCLEROSIS IN THE PHASE 3 FREEDOMS AND FREEDOMS II STUDIESAaron Boster,1 Kathleen Hawker,2 Shannon Ritter,2 Davorka Tomic,3 Till Sprenger4

1Department of Neurology, The Ohio State University Medical Center, Columbus, OH; 2Novartis Pharmaceuticals Corporation, East Hanover, NJ; 3Novartis Pharma AG, Basel, Switzerland; 4Medical Image Analysis Center, University Hospital Basel, Basel, Switzerland

Background: Magnetic resonance imaging (MRI) lesion activity and/or relapses occurring early in the course of multiple sclerosis (MS) have been proposed as predictors of long-term clinical out-comes. Objectives: To assess whether MRI disease activity and/or relapses during the first 12 months of the FREEDOMS and FREE-DOMS II studies predicted long-term clinical outcomes (relapses and 6-month confirmed disability progression [CDP]). Methods: This post hoc analysis used pooled data from the FREEDOMS and FREEDOMS II studies, in which patients were randomized to receive either oral fingolimod (0.5 mg or 1.25 mg) or placebo once daily. On entering the extension phases, patients were switched from placebo to fingolimod 0.5 mg. Unadjusted logistic regression was used to assess the ability of MRI disease activity (defined as one or more T1 Gd-enhancing lesions or two or more T2 lesions) and/or one or more relapses occurring during months 0 to 12 of treatment to predict the likelihood of clinical outcomes (relapses or 6-month CDP as measured by the Expanded Disability Status Scale [EDSS]) in months 12 to 24 and months 12 to 48. Results: A total of 2355 patients were randomized in FREEDOMS and FREEDOMS II, with 1693 patients entering the extension phases. During months 0 to 12, MRI disease activity or relapses alone were significantly predictive of relapses and 6-month CDP, both during months 12 to 24 (relapses: odds ratio [OR] 1.787, 95% confidence interval [CI] 1.420-2.248, P < .0001; 6-month CDP: OR 2.367, 95% CI 1.990-2.815, P < .0001) and during months 12 to 48 (relapses: OR 1.505, 95% CI 1.179-1.922, P = .0010; 6-month CDP: OR 2.812, 95% CI 2.182-3.623, P < .0001). Adding relapses to MRI activity improved predictive ability further (months 12–24: OR 3.285, 95% CI 2.454-4.397, P < .0001; months 12–48: OR 2.953, 95% CI 2.022-4.312, P < .0001). Conclusions: In the pooled FREEDOMS and FREEDOMS II population, MRI disease activity or relapses alone were predictors of both shorter-term (months 12–24) and longer-term (months 12–48) clinical disease activity. The combination of MRI disease activity and relapses also effectively predicted future relapses and disability progression.

Supported by: Novartis Pharmaceuticals CorporationDisclosure: Aaron Boster: Acorda Therapeutics, Actelion, Biogen Idec, CNS Therapeutics, Medtronic, Merck Serono, Novartis Pharmaceuticals Corporation, Jazz Pharmaceuticals, QuestCor, Roche, Sun-Pharma, Teva Pharmaceuticals (consulting fees). Kathleen Hawker: Novartis Pharmaceuticals Corporation (sal-ary). Shannon Ritter: Novartis Pharmaceuticals Corporation (salary). Davorka Tomic: Novartis Pharma AG (salary). Till Sprenger: Novartis, Actelion, ATI, Electrocore, Teva, Genzyme, Biogen Idec (consulting fees).Keywords: Fingolimod, MRI, Predictors, Relapses

(DX14) CLINICAL AND MRI BENEFITS OF IFNß-1A 44 µG SC TIW TREATMENT OVER 1 YEAR IN PATIENTS WITH RELAPSING MULTIPLE SCLEROSIS: SUBGROUP ANALYSES OF THE PRISMS STUDYMark Cascione,1 Fernando Dangond,2 Juanzhi Fang,2 Aaron Miller3

1Tampa Neurology Associates, South Tampa Multiple Sclerosis Center, South Tampa, FL; 2EMD Serono, Inc, Rockland, MA; 3Mount Sinai Hospital, New York, NY

Background: In the PRISMS-2 study, interferon beta-1a (IFNβ-1a) 44 and 22 µg given subcutaneously (SC) three times weekly (tiw)

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able treatment outcomes on DMF following natalizumab are not well understood. Objectives: Describe the retrospective, observational STRATEGY study of relapsing-remitting multiple sclerosis (RRMS) patients who switched from natalizumab to DMF in the real-world setting. The following factors potentially associated with treatment outcomes on DMF are to be included: patient demographics, disease activity prior to initiating natalizumab or while on natalizumab, duration of washout from natalizumab to DMF, and steroid treatment during washout. Methods: STRATEGY is being performed through a single-time-point medical chart abstraction without required study visits or procedures. Approximately 500 patients from approximately 50 US sites will be enrolled. Key inclusion criteria include age ≥18 years, RRMS diagnosis (McDonald criteria), at least 12 months of continuous treatment with natalizumab monotherapy prior to initiation of DMF, and initiation of DMF at least 12 months prior to enrollment. Patients are eligible to enroll regardless of current DMF use. Endpoints to be examined include relapse activity 12 months after initiation of DMF (measured as proportion of patients relapsed, annualized relapse rate, proportion of patients with MS-related hos-pitalization, and proportion of patients with relapses requiring intra-venous [IV] steroids); association between disease activity prior to initiating natalizumab or while on natalizumab and relapse activity on DMF; association between washout duration and relapse activity on DMF; and association between IV steroid use during the washout period and relapse activity while on DMF. Results: STRATEGY is ongoing; results will be reported. Conclusions: STRATEGY is being conducted to examine potential predictors of treatment response to DMF in RRMS patients who switched from natalizumab to DMF in the real-world setting.

Supported by: Biogen IdecDisclosure: Stanley Cohan: Biogen Idec, Novartis, Acorda, Genzyme (fees for non-CME services from commercial interests or their agents); Biogen Idec, Novartis, Genzyme (consulting fees); Genzyme, Biogen Idec, Mallinckrodt (grant/research support). Christopher LaGanke: Acorda, Bayer HealthCare, Biogen Idec, EMD Serono, Genzyme, Novartis, Pfizer, Questcor (fees for non-CME services from commercial interests or their agents); Acorda, Bayer HealthCare, Biogen Idec, EMD Serono, Genzyme, Novartis, Pfizer, Questcor, Teva Neurosci-ence (consulting fees); Bayer HealthCare, Biogen Idec, Genzyme, GSK, Novartis, Pfizer, Teva Neuroscience, Vaccinex (grant/research support). Carlo Tornatore: Biogen Idec (fees for non-CME services from commercial interests or their agents); Biogen Idec, Genzyme, Novartis (consulting fees). Jonathan Calkwood: Acorda, Bayer HealthCare, Biogen Idec, EMD Serono, Genzyme, Novartis, Questcor, Teva (consulting fees, fees for non-CME services from commercial interests or their agents); Biogen Idec, Novartis, Roche, Xenoport (grant/research support). Harold Moses: Biogen Idec, Teva, Bayer, EMD Serono, Genzyme, Novartis, Avanir (con-sulting fees, fees for non-CME services from commercial interests or their agents, grant/research support). Kyle E. Smoot: Acorda, Biogen Idec, EMD Serono, Gen-zyme, Novartis, Teva (consulting fees, fees for non-CME services from commercial interests or their agents). Monica Mann, Venkata Meka, Macaulay Okwuokenye, Christophe Hotermans, Leslie Meltzer: Biogen Idec (salary).Keywords: Disease-modifying treatments in MS

(DX17) FOUR-YEAR EXPANDED DISABILITY STATUS SCALE OUTCOMES IN PATIENTS TREATED WITH FINGOLIMOD IN THE PHASE 3 AND EXTENSION TRIAL PROGRAMBruce A.C. Cree,1 Jeffrey A. Cohen,2 Peter Chin,3 Shannon Ritter,3 Daniela Piani Meier,4 Ludwig Kappos5

1University of California San Francisco Medical Center, San Francisco, CA; 2The Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ; 4Novartis Pharma AG, Basel, Switzerland; 5University Hospital Basel, Basel, Switzerland

Background: Assessment of long-term disability status is impor-tant for characterizing the benefit-risk profile of disease-modifying therapies (DMTs) in multiple sclerosis (MS), although a lack of con-trol group and selective dropouts may produce bias. Objectives: To evaluate Expanded Disability Status Scale (EDSS) scores over time in patients with relapsing forms of MS who were treated with fingolimod in the phase 3 FREEDOMS, FREEDOMS II, and TRANS-FORMS studies and their extensions. Methods: EDSS data from

ranging from the individual making the decisions, the individual making the decisions jointly with the doctor, to the doctor making the decisions. Results are reported for online responders (analysis for paper forms is ongoing). Results: Of 5108 online responders, 4907 (96.1%) had complete CPS and demographics. The mean (SD) age was 57.0 (9.6) years, 60.3% (2957) had relapsing-remitting MS (RRMS), 78.1% were female, and 69.3% reported DMT use in the prior 6 months. Of those with RRMS, 24.9% (n = 544) reported a DMT change during that period that was similar for other types of MS (P = .09). For CP (median age for response): 42.6% (median age 58.4) share responsibility with the doctor in treatment decisions, 41.7% (56.3) make the final decision after considering the doctor’s opinion, 8.5% (57.9) make the final decision alone, 6.2% (59.5) prefer that the doctor make the decision considering their opinion, and 1.1% (63.1) leave all decisions to the doctor. CP did not differ by gender (P = .09) or relapse in the last 6 months (P = .86), but older participants were more likely to leave all decisions to the doc-tor (all P < .01). When adjusted for age (P < .0001) and type of MS (P = .028), those currently on a DMT were more likely to share the decision with the doctor than those who were not on a DMT (47.4% vs. 31.6%, P < .0001). Conclusions: Most responders shared treat-ment decisions with their doctor or considered their doctor’s opinion before making a decision. Younger responders, those currently on a DMT, and those with RRMS reported more frequent shared decision-making than older responders, those not on a DMT, or those with other types of MS.

Supported by: CMSC and the Foundation of the CSMCDisclosure: Stacey S. Cofield: MedImmune, American Shoulder Elbow Society (consulting fees). Tuula Tyry, Sandre McNeal: Nothing to disclose. Nina Thomas: Genentech, Inc (salary). Robert J. Fox: Actelion, Biogen Idec, Novartis (advisory committees, fees for non-CME services from commercial interests or their agents); Actelion, Biogen Idec, MedDay, Novartis, Questcor, Teva, XenoPort (consult-ing fees); Novartis (grant/research support). Ruth Ann Marrie: CIHR, PHAC, MHRC, HSC Foundation, MS Society of Canada, MS Scientific Foundation, CMSC Foundation, Rx & D Health Research Foundation, Bayer Inc, Sanofi-Aventis, EMD Serono (grant/research support). Gary Cutter: Antisense Thera-peutics Limited, Sanofi-Aventis, Bayhill Pharmaceuticals, Bayer Pharmaceuticals, BioMS Pharmaceuticals, Daichi-Sankyo, GlaxoSmithKline Pharmaceuticals, Genmab Biopharmaceuticals, Medivation, Peptimmune, PTC Therapeutics, Teva, Vivus, National Heart, Lung, and Blood Institute, National Institute of Neurological Disorders and Stroke, National Multiple Sclerosis Society (DSMB service); EMD Serono, EDJ Associates, Aegis Creative Marketing, Eli Lilly, UT Southwestern University, Klein Buendel, University of Illinois Health Policy Cen-ter, Somnus Therapeutics, Klein-Buendel Incorporated, Enzo Pharmaceuticals, Somnus Pharmaceuticals, Teva, Biogen Idec, Advanced Health Media, PTC Therapeutics, Teva, Vivus, National Heart, Lung, and Blood Institute, National Institute of Neurological Disorders and Stroke, National Multiple Sclerosis Soci-ety, Alexion, Accentia, Barofold, CibaVision, Biogen Idec, Novartis, Consortium of Multiple Sclerosis Centers (consulting fees).Keywords: Comprehensive care and MS, Disease-modifying treatments in MS, Epidemiology of MS

(DX16) REAL-WORLD CLINICAL OUTCOMES IN RELAPSING-REMITTING MULTIPLE SCLEROSIS PATIENTS WHO SWITCH FROM NATALIZUMAB TO DELAYED-RELEASE DIMETHYL FUMARATEStanley Cohan,1 Christopher LaGanke,2 Carlo Tornatore,3 Jonathan Calkwood,4 Harold Moses,5 Kyle E. Smoot,6 Monica Mann,7 Venkata Meka,8 Macaulay Okwuokenye,8 Christophe Hotermans,7 Leslie Meltzer8

1Providence Brain and Spine Institute, Providence Multiple Sclerosis Center, Portland, OR; 2North Central Neurology Associates, Cullman, AL; 3Department of Neurology, Medstar Georgetown University Hospital, Washington, DC; 4Schapiro Center for Multiple Sclerosis, Minneapolis Clinic of Neurology, Golden Valley, MN; 5Department of Neurology, Neuroimmunology Division, Vanderbilt University Medical Center, Nashville, TN; 6Providence Multiple Sclerosis Center, Portland, OR; 7Biogen Idec, Weston, MA; 8Biogen Idec, Cambridge, MA

Background: Standardized practices for transitioning patients from natalizumab to delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) are lacking. Clinical practices and switch protocols vary across the population, and predictors of favor-

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on oral medication, 90 (43%) on a SC/IM drug, and the remain-ing 30 (14.5%) on an IV infusion. Fifty-five percent of patients on oral DMTs reported no missed doses, as compared with 70.8% of patients taking SC/IM and 93.3% on patients receiving IV infusions (P = .005). Reason for missed dose differed with respect to medica-tion type (P = .017), with forgetfulness being reported in 37.6% and 26.5% of patients receiving oral and IM/SC DMTs, respectively. In addition, side effects were significantly different for each medication type (P < .0001). The overwhelming majority of those receiving IV infusions did not experience side effects (74.3%), whereas only a minority of those taking oral medications (18.6%) and SC/IM drugs (20.2%) responded as such. Ease of taking medication was reported by 77%, 60%, and 33% of patients on oral, IV, and SC/IM thera-pies, respectively (P < .0001). Patient satisfaction did not significantly vary by medication type (P = .235). Conclusions: In our popula-tion, lack of adherence was significantly higher in patients receiving oral as compared to injectable DMTs, despite their reported ease of administration. Side effect profile may have been a contributing fac-tor to this outcome. Health-care providers should implement strategies to improve DMT adherence, regardless of medication route.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Disease-modifying treatments in MS, Nursing management in MS

(DX20) A DESCRIPTIVE ANALYSIS OF TIME TO FIRST TREATMENT WITH DISEASE-MODIFYING DRUGS IN NEWLY DIAGNOSED PATIENTS WITH MULTIPLE SCLEROSISNatalie C. Edwards,1 Amy L. Phillips,2 Samuel Sutherland3

1Health Services Consulting Corporation, Boxborough, MA; 2EMD Serono, Inc, Rockland, MA; 3Boston Health Economics, Inc, Waltham, MA

Background: Evidence suggests that early treatment with disease-modifying drugs (DMDs) following a diagnosis of relapsing multiple sclerosis (MS) is recommended for most patients with MS. Objec-tives: To examine the time to first DMD prescription in newly diag-nosed patients with MS. Methods: This retrospective database analysis of newly diagnosed patients with MS was conducted using a national managed-care database. Patients aged 18 to 64 years, with a first MS claim (ICD-9-CM: 340.xx) between 1/1/2008 and 12/31/2011 (index date), with continuous eligibility for 6 months pre- and 24 months post-index, and who had at least one DMD claim during the 24-month post-index period were included in the analysis. Patients who had evidence of DMD use prior to their first MS claim were excluded. Categorical and binary variables were summarized using frequencies and percentages. Continuous variables were summarized using means, standard deviations (SDs), and medians. Results: A total of 7993 patients with MS met study inclusion criteria. Mean age was 42.7 years (SD 10.2), and 75.5% were female. Patients were most likely to be from the Midwest (32.6%) or Northeast (30.3%) regions, which reflects sampling for the national database used in this study. The average time from first MS diag-nosis to first DMD claim was 150 days (SD 181), with a median time of 64 days. Examining the time to first DMD treatment showed that 28.2% received their first DMD in less than 30 days, 48.1% in less than 60 days, 58.7% in less than 90 days, and 71.6% in less than 180 days. Over one-quarter of patients (28.4%) did not have their first DMD claim for 180 or more days following their first MS diagnosis. A secondary analysis examined time to first DMD claim for newly treated patients with any available data in the post-index period (n = 9359). The mean and median time to DMD treatment for this broader population was 295.5 (SD 408.4) and 89 days, respec-tively. Conclusions: This study demonstrates that many patients with newly diagnosed MS have a delay before having their first DMD claim, with 28.4% waiting to start therapy for at least 6 months. Data suggest that early initiation of DMD therapy following a diagnosis of relapsing MS is important for optimizing MS management.

Supported by: EMD Serono, Inc, a subsidiary of Merck KGaA; Pfizer IncDisclosure: Natalie C. Edwards: Health Services Research (consulting fees). Amy

patients initiating fingolimod in the phase 3 core or extension studies were pooled for post hoc analysis. Kaplan-Meier estimates of the proportions of patients not reaching EDSS scores 4, 6, and 7 dur-ing fingolimod treatment were calculated for patients who received fingolimod 0.5 mg and those who received fingolimod at any dose. A descriptive analysis is provided for the proportions of patients at 24, 36, and 48 months with an EDSS score less than or equal to the score at fingolimod treatment initiation. Results: Mean and median treatment exposure were 920 days and 967 days in patients receiv-ing fingolimod 0.5 mg (n = 1641) and 882 days and 918 days in those receiving all fingolimod doses (n = 3283). Kaplan-Meier estimates of proportions of patients not reaching EDSS scores 4, 6, and 7 were 71.3%, 87.8%, and 96.7% for fingolimod 0.5 mg and 69.5%, 87.0%, and 96.3% for all fingolimod doses, respectively. At month 24, month 36, and month 48 the proportions of patients with EDSS score less than or equal to the baseline value were 67.9% (n = 1324), 64.7% (n = 909), and 66.8% (n = 587) for fingolimod 0.5 mg and 69.0% (n = 2580), 66.4% (n = 1727), and 66.2% (n = 1110) for all fingolimod doses. Of these, EDSS was improved at months 24, 36, and 48 compared with the baseline value in 15.7%, 17.4%, and 17.4% of patients treated with fingolimod 0.5 mg, and 17.5%, 18.7%, and 18.5% of those receiving all fingolimod doses. Conclusions: Most patients treated with fingolimod for up to 4.9 years remained free of the need for walking assistance. Approxi-mately two-thirds of patients who continued fingolimod treatment had the same or a better EDSS score after 2, 3, and 4 years of treatment, of which 16% to 18% showed improvement. Absence of a control group and selective dropouts may bias these results.

Supported by: Novartis Pharmaceuticals CorporationDisclosure: Bruce A.C. Cree: Biogen Idec, Elan Corporation, Genzyme, Sanofi-Aventis, Teva Pharmaceuticals, BioMS Medical, EMD Serono, Genentech, National Institutes of Health, National Multiple Sclerosis Society (consulting fees). Jeffrey A. Cohen: EMD Serono, Genzyme, Genentech, Innate Immunotherapeu-tics, Novartis Pharmaceuticals Corporation, Vaccinex, Biogen Idec, Consortium of Multiple Sclerosis Centers, US Department of Defense, Genzyme, Receptos, Synthon, Teva Pharmaceuticals (consulting fees). Peter Chin, Shannon Ritter, Daniela Piani Meier: Novartis Pharmaceuticals Corporation (salary). Ludwig Kappos: Nothing to disclose.Keywords: Disability, Expanded Disability Status Scale, Fingolimod

(DX18) WITHDRAWN

(DX19) DO ORAL DISEASE-MODIFYING AGENTS IMPROVE ADHERENCE TO MULTIPLE SCLEROSIS TREATMENT? A COMPARISON OF ORAL AND INJECTABLE DRUGSCaitlin A. Dionne, Rik Ganguly, Ann Camac, Claudia Chaves

Neurology, Lahey Clinic, Lexington, MA

Background: Lack of adherence to treatment, particularly with injectable medications, has been a significant problem in multiple sclerosis (MS) and estimated to occur in 20% to 50% of patients with consequent increase in relapse rate and disease progression. In recent years, therapeutic options for MS have expanded to include three oral options. The impact of oral disease-modifying therapies (DMTs) in improving adherence to MS treatment is not well known. Objectives: To determine whether adherence and tolerability of oral DMTs is better than with injectables in our MS center population. Methods: We developed the MS Treatment Adherence Question-naire (MS-TAQ) and collected data from October to November 2014. The MS-TAQ is composed of six questions: patient’s current DMT, number of missed doses in 4 weeks, reason dose was missed, perceived side effects, ease of administration, and medication satisfaction. Medication types were divided into three groups: sub-cutaneous or intramuscular (SC/IM), monthly IV injections, and oral DMTs. We analyzed the responses using the Fisher exact test (α = .05) to determine whether responses varied by medication type. Results: We had 209 patients, 75.1% female and 24.9% male, with a mean age of 50.4 years. Eighty-nine patients (42.5%) were

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Nuwan C. Kurukulasuriya: Biogen Idec (salary).Keywords: Disease-modifying treatments in MS

(DX22) RESOURCE USE, EMPLOYMENT STATUS, AND ESCALATION TO SECOND-LINE THERAPY IN PATIENTS FROM THE BENEFIT STUDY 11 YEARS AFTER ONSET OF MULTIPLE SCLEROSIS SYMPTOMSEdward J. Fox,1 Gilles Edan,2 Mark S. Freedman,3 Xavier Montalbán,4 Hans-Peter Hartung,5 Bernhard Hemmer,6,7 Frederik Barkhof,8 Sven Schippling,9 Andrea Schulze,10 Dirk Pleimes,11 Christoph Pohl,12,13 Rupert Sandbrink,5,13 Gustavo Suarez,14 Eva-Maria Wicklein,13 Ludwig Kappos15

1Central Texas Neurology Consultants, University of Texas Medical Branch, Round Rock, TX; 2CHU-Hôpital Pontchaillou, Rennes, France; 3Division of Neurology, Ottawa Hospital Research Institute, Ottawa, ON, Canada; 4Hospital Universitari Vall d’Hebron, Barcelona, Spain; 5Heinrich-Heine University, Düsseldorf, Germany; 6Technische Universität München, Munich, Germany; 7Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; 8Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands; 9University Hospital Zurich, Zurich, Switzerland; 10PAREXEL International, Berlin, Germany; 11Myelo Therapeutics GmbH, Berlin, Germany; 12Department of Neurology, University Hospital of Bonn, Bonn, Germany; 13Bayer Pharma AG, Berlin, Germany; 14Bayer HealthCare Pharmaceuticals, Whippany, NJ; 15Neurology, University Hospital Basel, Basel, Switzerland

Background: The BENEFIT trial demonstrated improved clinical outcomes in patients with a first event suggestive of multiple sclerosis (MS) (a clinically isolated syndrome [CIS]) who had early treatment with interferon beta-1b (IFNβ-1b) up to 11 years after randomiza-tion. Objectives: To describe employment status, resource use, and escalation to second-line therapy 11 years after CIS to establish the long-term effects of early treatment with IFNβ-1b. Methods: Patients with CIS had been randomly assigned to receive IFNβ-1b 250 µg (early treatment) or placebo (delayed treatment). After con-version to clinically definite MS or a maximum of 2 years, patients receiving placebo were offered active treatment. 11 years after the initial randomization, all patients from participating study centers were approached to participate in the study. Results: 278 of the 468 patients originally enrolled in BENEFIT were evaluated (median age at onset 30 years). Both treatment groups had similar levels of resource use and employment status at year 11. Most patients (239 [86.0%]) lived with either a partner or family. 204 patients (73.4%) were employed at year 11, compared with 81.3% at study entry. Of those, 64.4% were working >20 hours/week and 9.0% <20 hours/week (vs. 75.9% and 5.4%, respectively, at study entry). 26 patients (9.4%) were retired at year 11 (22 [7.9%] retired early), compared with 7 (2.5%) at study entry. 12 patients (4.3%) were on long-term disability. In the 12 months prior to the year 11 assessment, 178 patients (64.0%) reported that they did not take any days off work (including school and housework) due to MS and 254 (91.4%) did not need hospitalization. 21 (7.6%) had home, car, or work adaptations. 14.3% of patients required escalation to second-line therapies (including natalizumab, cyclophosphamide, mitoxantrone, alemtuzumab, cyclosporine, methotrexate, mycophenolate mofetil/mycophenolate sodium, cladribine, daclizumab, rituximab, sirolimus, tacrolimus, temsirolimus, or fingolimod). Conclusions: Employment rate at study start reflected European averages and at year 11 remained comparatively high while resource use was relatively low. Findings suggest that early treatment with IFNβ-1b can stabilize the disease enough to allow the majority of patients to remain employed, minimize their resource use over the long term, and avoid escalation to a second-line therapy.

Disclosure: Edward J. Fox: Bayer HealthCare, Biogen Idec, Eli Lilly, EMD Serono, Genzyme, Novartis, Ono, Opexa Therapeutics, Pfizer, Sanofi, Teva (con-sulting fees, grant/research support, honoraria, travel support). Gilles Edan: Biogen Idec, Merck Serono, Sanofi-Aventis, Bayer HealthCare Pharmaceuticals (consult-ing fees); Serono, Teva (grant/research support). Mark S. Freedman: Actelion, Bayer HealthCare, Biogen Idec, EMD Canada, Genzyme, Merck Serono, Novar-tis, Sanofi-Aventis, Teva Canada Innovation (consulting fees); Bayer HealthCare, Genzyme (grant/research support); Genzyme (fees for non-CME services from com-mercial interests or their agents). Xavier Montalbán: Bayer, Biogen Idec, EMD, Genentech, Genzyme, Merck Serono, Neurotec, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, Almirall (consulting fees). Hans-Peter Hartung: Bayer Pharma

L. Phillips: EMD Serono, Inc, a subsidiary of Merck KGaA (salary). Samuel Sutherland: EMD Serono (grant/research support).Keywords: Disease-modifying treatments in MS

(DX21) RATE OF BRAIN VOLUME LOSS UNDER LONG-TERM DELAYED-RELEASE DIMETHYL FUMARATE TREATMENT IN RELAPSING-REMITTING MULTIPLE SCLEROSIS PATIENTS: RESULTS FROM THE ENDORSE STUDYRobert J. Fox,1 Ludwig Kappos,2 Ralf Gold,3 Douglas L. Arnold,4 James Potts,5 Annie Zhang,5 Nuwan C. Kurukulasuriya5

1Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH; 2University Hospital Basel, Basel, Switzerland; 3St. Josef Hospital, Ruhr University, Bochum, Germany; 4Montreal Neurological Institute, McGill University, Montreal, QC, Canada; 5Biogen Idec, Cambridge, MA

Background: Brain atrophy in multiple sclerosis (MS) has been shown to correlate with physical disability, cognitive deficits, and quality of life. Changes in brain volume, typically calculated by mag-netic resonance imaging (MRI) techniques, may be used as indirect measures of brain atrophy. Objectives: Evaluate the long-term effect on brain volume loss in patients receiving continuous delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) treat-ment compared with patients switching from placebo or glatiramer acetate (GA) in the ENDORSE study, an extension of the phase 3 DEFINE and CONFIRM studies. Methods: Patients randomized to DMF 240 mg twice (BID) or three times (TID) daily in DEFINE/CON-FIRM continued the same dosage in ENDORSE; patients randomized to placebo (PBO) or GA (CONFIRM only) were re-randomized 1:1 to DMF bid or tid. Data were analyzed (May 14, 2014, cutoff) by treat-ment in parent/extension study. At year 3 (week 144) of ENDORSE, BID/BID patients received ≥5 years of continuous DMF treatment; PBO/BID and GA/BID patients received 2 years of PBO (DEFINE/CONFIRM) or GA (CONFIRM), respectively, followed by ≥3 years of DMF (ENDORSE). Percentage brain volume change (PBVC) was cal-culated at year 3 of ENDORSE relative to the predefined baseline for PBVC, week 24 of DEFINE/CONFIRM. Results from patients treated with DMF 240 mg BID are reported, as this represents the mainte-nance dose of DMF that is approved for the treatment of patients with relapsing MS. Results: This analysis was conducted in the MRI cohort of ENDORSE. Normalized brain volume data were avail-able for 195 (BID/BID), 87 (PBO/BID), and 42 (GA/BID) patients. Mean PBVC at year 3 (over 218 weeks or 4.5 years) of ENDORSE relative to week 24 of DEFINE/CONFIRM was −1.38 (BID/BID), −1.90 (PBO/BID), and −2.05 (GA/BID). In the BID/BID group in ENDORSE, the rate of brain volume loss was slowed compared with placebo (P = .0304) and significantly slowed across all time points compared with PBO/BID and GA/BID. Conclusions: This analysis suggests a continuous beneficial effect of DMF on brain atrophy and a higher impact of early DMF treatment compared with delayed DMF treatment.

Supported by: Biogen IdecDisclosure: Robert J. Fox: Actelion, Biogen Idec, Novartis (advisory committees, fees for non-CME services from commercial interests or their agents); Actelion, Bio-gen Idec, MedDay, Novartis, Questcor, Teva, XenoPort (consulting fees); Novartis (grant/research support). Ludwig Kappos: Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Genzyme, Merck, Mitsubishi, Novartis, Ono Pharma, Roche, Receptos, Sanofi-Aventis, Santhera, Siemens, Teva (fees for non-CME services from commercial interests or their agents); Actelion, Addex, Bayer HealthCare, Biogen, Genzyme, Merck, Mitsubishi, Novartis, Ono Pharma, Roche, Receptos, Sanofi-Aventis, Santhera, Siemens, Teva, XenoPort (consulting fees); Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Pfizer, Roche, Sanofi, Teva, UCB (support of educational activities); Bayer HealthCare, Biogen, Merck, Novartis, Roche, Swiss MS Society, Swiss National Research Foundation, European Union, Roche Research Foundation (grant/research support); Neurosta-tus Systems GmbH (royalty). Ralf Gold: Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, Teva Neuroscience (fees for non-CME services from commercial interests or their agents, grant/research support); Sage (compensation for serving as editor of Therapeutic Advances in Neurological Disorders). Douglas L. Arnold: Acorda Therapeutics, Biogen Idec, Genzyme, MedImmune, Mitsubishi, NeuroRx Research, Novartis, Roche, Teva (consulting fees). James Potts, Annie Zhang,

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treatment by subgroup interaction. Conclusions: Both doses of teriflunomide had a consistently positive effect on time to first relapse and time to relapse or occurrence of a new MRI lesion across patient subgroups defined by gender, age, monofocal/multifocal status, and baseline MRI variables.

Supported by: Genzyme, a Sanofi companyDisclosure: Edward J. Fox: Acorda, Bayer, Biogen Idec, EMD Serono, Genzyme, Novartis, Sanofi, Teva (consulting fees, fees for non-CME services from com-mercial interests or their agents); Biogen Idec, Chugai, Eli Lilly, EMD Serono, Genzyme, Novartis, Opexa, Roche, Sanofi, Teva (grant/research support). Aaron E. Miller: Accordant Health Services, Biogen Idec, EMD Serono (Merck Serono), Genzyme/Sanofi-Aventis, GSK, Novartis, Nuron Biotech, Questcor, Teva (con-sulting fees); Acorda Therapeutics, Biogen Idec, Genentech, Genzyme, Novartis, Questcor, Roche, Sanofi-Aventis (grant/research support). Philippe Truffinet, Karthinathan Thangavelu: Genzyme, a Sanofi company (salary). Mark S. Freed-man: Bayer HealthCare, Biogen Idec, Hoffman La-Roche, Merck Serono, Novar-tis, Opexa, Sanofi-Aventis (advisory board or board of directors); Genzyme (speak-ers’ bureau, fees for non-CME services from commercial interests or their agents); Bayer HealthCare, Biogen Idec, Chugai, EMD Canada, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva Canada Innovation (consulting fees).Keywords: Disease-modifying treatments in MS

(DX24) AN ASSESSMENT OF FACTORS ASSOCIATED WITH HIGH COSTS AMONG PATIENTS WITH MULTIPLE SCLEROSIS RECEIVING DISEASE-MODIFYING DRUG THERAPYMolly Frean,1 Julie C. Locklear,2 Amy L. Phillips,2 Joseph Menzin1

1Boston Health Economics, Inc, Waltham, MA; 2EMD Serono, Inc, Rockland, MA

Background: There are limited data on factors associated with high medical costs of care in a multiple sclerosis (MS) population. Claims-based markers for health status may be useful to understand costs. Objectives: To compare patient characteristics and frequency of diagnoses between high- and non-high-cost MS patients receiv-ing disease-modifying drugs (DMDs). Methods: MS patients (age 18–63; ≥1 MS diagnosis claim: ICD-9-CM: 340.xx) with ≥1 DMD claim (first claim = index date) and continuous eligibility 12 months pre- and post-index were identified from a random sample of 5 million lives in the IMS LifeLink Plus database from 1/1/2007 to 6/30/2012. Patients with all-cause total costs (excluding DMD costs) ≥75th percentile were considered high-cost. Diagnoses codes (ie, “condition indicators”) were grouped into three domains: MS-related conditions (eg, disability), Clinical Classification System (CCS) code categories (eg, gastrointestinal), and Charlson-Deyo comorbidities. Fisher and Wilcoxon tests were used in unadjusted statistical com-parisons. Logistic regression was used to evaluate likelihood of being a high-cost patient. Covariates included demographics, condition indicators, dalfampridine use, newly initiating DMDs and adherence. Results: Analysis included 24,815 patients. 75th percentile for high-cost status was $11,740, yielding 6207 high-cost and 18,608 non-high-cost patients (mean age: 46.3 vs. 44.2, respectively; P < .001). In unadjusted analyses, percentage of patients with each condition indicator was statistically significantly higher in the high-cost group (P < .05). In logistic regression analyses, age and sex were not consistently predictive of being high-cost. High counts of conditions within each domain (eg, ≥5 MS-related conditions: odds ratio [OR]: 5.801; P < .0001) and selected individual conditions (eg, disability: OR: 1.809; P < .0001) were associated with significantly higher likelihood of being high-cost. Use of dalfampridine, a symp-tomatic agent, was also significantly associated with being high-cost (OR: 5.744–6.062 across specifications; P < .0001). Conversely, better adherence (medication possession ratio ≥80%) and newly ini-tiating DMDs were associated with a lower likelihood of being high-cost (OR: 0.570–0.594 and 0.850–0.898 across specifications, respectively; all P < .01). Conclusions: MS-related conditions, CCS categories, and Charlson-Deyo comorbidities were independently associated with high costs. Interventions targeting individuals affected by key conditions may be important to reduce costs and disease burden.

AG, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Teva, Sanofi-Aventis (consulting fees). Bernhard Hemmer: Bayer Schering, Novartis, Biogen Idec, Merck Serono, Roche, Teva Pharmaceutical Industries Ltd (fees for non-CME services from commercial interests or their agents); Biogen Idec, Bayer Schering, Merck Serono, Five Prime, Metanomics, Novartis (grant/research support, receipt of intellectual property rights/patents); Roche, Novartis, Bayer Schering, Merck Serono, Biogen Idec, GSK, Chugai Pharmaceuticals, Micromet, Genzyme Corpo-ration (consulting fees). Frederik Barkhof: Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis, Genzyme, Roche, Teva (consulting fees). Sven Schippling: Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Teva, Sanofi-Aventis (consulting fees); Biogen Idec, Bayer Schering Pharma, Gen-zyme (grant/research support). Andrea Schulze: PAREXEL International (salary). Dirk Pleimes: Bayer AG (ownership interest); Bayer Pharma AG/Bayer Health-Care Pharmaceuticals (consulting fees, salary). Christoph Pohl, Rupert Sandbrink: Bayer Pharma AG/Bayer HealthCare Pharmaceuticals (ownership interest, sala-ry). Gustavo Suarez: Bayer Pharma AG/Bayer HealthCare Pharmaceuticals (sala-ry). Eva-Maria Wicklein: Bayer Pharma AG (salary). Ludwig Kappos: Santhera, Siemens, Teva (compensation to institution); Actelion, Addex, Bayer HealthCare Pharmaceuticals, Bayer Schering Pharma, Biogen Idec, CLC Behring, Genentech, GeNeuro SA, Genzyme, Merck Serono, Mitsubishi Pharma, Novartis, Octaphar-ma, Praxicon, Roche, Sanofi-Aventis (compensation to institution, consulting fees); Novartis, Roche Research Foundations (grant/research support).Keywords: Disease-modifying treatments in MS, Economic issues and MS, Employment in MS

(DX23) CONSISTENT EFFICACY OF TERIFLUNOMIDE IN PRESPECIFIED SUBGROUP ANALYSES FROM A PHASE 3 TRIAL (TOPIC) IN PATIENTS WITH EARLY MULTIPLE SCLEROSISEdward J. Fox,1 Aaron E. Miller,2 Philippe Truffinet,3 Karthinathan Thangavelu,4 Mark S. Freedman5

1Multiple Sclerosis Clinic of Central Texas, Central Texas Neurology Consultants, Round Rock, TX; 2Icahn School of Medicine at Mount Sinai, The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, New York, NY; 3Genzyme, a Sanofi company, Chilly-Mazarin, France; 4Genzyme, a Sanofi company, Cambridge, MA; 5University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada

Background: Teriflunomide is a once-daily oral immunomodu-lator approved for the treatment of relapsing-remitting MS. The TOPIC study (NCT00622700) evaluated the efficacy and safety of teriflunomide in patients with a first clinical episode suggestive of MS. Teriflunomide 14 mg reduced the risk of relapse indicating clinically definite MS (CDMS) by 42.6% (P = .0087) and the risk of relapse or occurrence of a new magnetic resonance imaging (MRI) lesion (whichever occurred first) by 34.9% (P = .0003) compared with placebo. Teriflunomide 7 mg reduced the risk of relapse indicat-ing CDMS by 37.2% (P = .0271) and of relapse or MRI lesion by 31.4% (P = .0020) compared with placebo. Objectives: To report prespecified subgroup analyses of teriflunomide treatment effects in TOPIC. Methods: Patients (n = 614) were randomized (1:1:1) and treated with once-daily teriflunomide 14 mg, 7 mg, or placebo for ≤108 weeks. The effect of teriflunomide on time to relapse indicat-ing conversion to CDMS (primary endpoint) and on time to relapse or occurrence of a new MRI lesion (key secondary endpoint) was analyzed in subgroups defined by gender, age (< or ≥31 years), geographic region (Eastern Europe, Western Europe, the Americas, and Australia), monofocal/multifocal status, and baseline number of gadolinium-enhancing lesions (0 or ≥1) and total lesion volume (< or ≥5 mL). Consistency of treatment effects across subgroups was assessed using a Cox regression model utilizing a treatment-by-subgroup interaction test for each factor separately. The model included treatment, baseline monofocal/multifocal status, region, subgroup, and treatment-by-subgroup interaction as covariates. Results: Patient characteristics were well balanced across treatment groups. The benefits of treatment on time to relapse were consistent across all predefined subgroups whether stratified according to demographic features or baseline disease characteristics, except for Eastern Europe in the teriflunomide 7-mg group (P value for interac-tion = .0047), in which very few relapses were reported overall. The treatment effect was also observed across all subgroups for time to relapse or occurrence of a new MRI lesion, with no significant

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(DX26) CLINICAL AND MRI EFFICACY OF INTERFERON BETA-1A SUBCUTANEOUSLY THREE TIMES WEEKLY IN MULTIPLE SCLEROSIS PATIENTS WITH MORE ADVANCED DISEASE (EDSS 4.0–6.0)Mark S. Freedman,1 Brooke Hayward,2 John Warth,2 Fernando Dangond2

1University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada; 2EMD Serono, Inc, Rockland, MA

Background: Interferon beta-1a (IFNβ-1a) 44 µg subcutaneously (SC) 3 times weekly (tiw) reduced relapses and active T2 lesions in PRISMS over 2 years and in SPECTRIMS over 3 years, but signifi-cantly delayed disability progression versus placebo only in PRISMS. Understanding treatment effect in patients with more advanced disease (higher Expanded Disability Status Scale [EDSS]) is of inter-est. Objectives: Use combined PRISMS and SPECTRIMS data to further characterize IFNβ-1a 44 µg efficacy in patients with more advanced disease. Methods: In PRISMS, 560 relapsing multiple sclerosis (RMS) patients with EDSS 0–5.0 and ≥2 relapses in the past 2 years were randomly assigned to IFNβ-1a 44 or 22 µg or placebo for 2 years. In SPECTRIMS, 618 patients with secondary progressive MS (SPMS) (EDSS increase ≥1 point over last 2 years [≥0.5 point if baseline (BL) EDSS 6.0–6.5]) and BL EDSS 3.0–6.5 were randomly assigned to IFNβ-1a 44 or 22 µg or placebo for 3 years. These post hoc analyses examined relapses, T2 lesions, and 3-month confirmed progression (≥1 point EDSS increase [0.5 if BL ≥6.0]) at 1 and 2 years in patients receiving IFNβ-1a 44 µg or placebo in a combined subgroup with EDSS 4.0–6.0. Results: IFNβ-1a (n = 171) reduced the annualized relapse rate versus placebo (n = 164) by 36.6% (rate ratio [RR] 0.632 [95% confidence interval (CI) 0.496-0.805]; P = .0002) at 1 year and 36.2% (RR 0.638 [0.507-0.803]; P = .0001) at 2 years in the combined EDSS 4.0–6.0 subgroup. IFNβ-1a reduced mean (SD) numbers of active T2 lesions versus placebo at months 6 (IFNβ-1a, 0.6 [1.3] vs. placebo, 2.4 [5.2]), 12 (0.5 [1.4] vs. 2.3 [4.1]), and 24 (0.5 [1.5] vs. 1.4 [2.9]). IFNβ-1a reduced burden of disease (total T2 lesion area) from BL significantly more versus placebo through month 24 (–31.1 [883.96] vs. 455.8 [1110.9] mm2; P < .0001). Further, IFNβ-1a reduced disability progression risk at 1 year (hazard ratio [HR] 0.654 [95% CI 0.429-0.997]; P = .0486 vs. placebo) although not significantly at 2 years (HR 0.740 [0.530-1.035]; P = .0785). Data from patients with EDSS 4.0–6.0 still experiencing inflammatory activity (relapses or active MRI lesions) will be presented. Results of 6-month confirmed disability progression and time to EDSS progression will also be shown. Con-clusions: Post hoc analyses indicate that the effect of IFNβ-1a 44 µg SC tiw to reduce relapses and T2 lesions and delay EDSS progres-sion is not lost in a subgroup of MS patients with more advanced disease (EDSS 4.0–6.0), despite the inclusion of SPMS subjects in the pooled data set.

Supported by: EMD Serono, Inc, a subsidiary of Merck KGaA; Pfizer IncDisclosure: Mark S. Freedman: Bayer HealthCare (grant/research support); Novartis, Teva Canada Innovation, Sanofi-Aventis, Bayer HealthCare, Biogen Idec, EMD Serono (Canada), Genzyme, Opexa (personal compensation). Brooke Hayward, John Warth, Fernando Dangond: EMD Serono, Inc, a subsidiary of Merck KGaA (salary).Keywords: Disease-modifying treatments in MS, Interferon beta

(DX27) TERIFLUNOMIDE EFFICACY IN NEWLY DIAGNOSED PATIENTS WITH RELAPSING MULTIPLE SCLEROSIS ENROLLED IN THE TEMSO AND TOWER STUDIES: A POST HOC ANALYSISJerry S. Wolinsky,1 Mark S. Freedman,2 Giancarlo Comi,3 Jean-Pierre Bouchard,4 Ludwig Kappos,5 Philippe Truffinet,6 Karthinathan Thangavelu,7 Steven Cavalier,7 Paul O’Connor8

1University of Texas Health Science Center at Houston, Houston, TX; 2University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada; 3University Vita-Salute San Raffaele, Milan, Italy; 4Laval University, Centre Hopitalier Universitaire de Québec, Québec City, QC, Canada; 5University Hospital Basel, Basel, Switzerland; 6Genzyme, a Sanofi company, Chilly-Mazarin, France; 7Genzyme, a Sanofi company, Cambridge, MA; 8Division of Neurology, St. Michael’s Hospital, Toronto, ON, Canada

Disclosure: Molly Frean, Joseph Menzin: EMD Serono (funding); Boston Health Economics, Inc (salary). Julie C. Locklear, Amy L. Phillips: EMD Serono, Inc, a subsidiary of Merck KGaA (salary).Keywords: Economic issues and MS

(DX25) EFFICACY AND SAFETY OF TERIFLUNOMIDE IN PATIENTS SWITCHING FROM OTHER DISEASE-MODIFYING THERAPIESMark S. Freedman,1 Jerome de Seze,2 Tomas P. Olsson,3 Anna Czlonkowska,4 Patrick Vermersch,5 Myriam Benamor,6 Philippe Truffinet,6 Karthinathan Thangavelu,7 Ludwig Kappos8

1University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada; 2University Hospitals of Strasbourg, Strasbourg, France; 3Karolinska Institute, Stockholm, Sweden; 4Institute of Psychiatry and Neurology Warsaw, Warsaw, Poland; 5University of Lille, Lille, France; 6Genzyme, a Sanofi company, Chilly-Mazarin, France; 7Genzyme, a Sanofi company, Cambridge, MA; 8University Hospital Basel, Basel, Switzerland

Background: Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting multiple sclerosis (MS). In TEMSO (NCT00134563) and TOWER (NCT00751881) phase 3 studies, teriflunomide 14 mg significantly reduced annualized relapse rate (ARR) and risk of disability progression versus placebo in patients with relapsing forms of MS (RMS). The TENERE (NCT00883337) phase 3 study showed comparable results on time to failure between teriflunomide and subcutaneous interferon beta-1a (IFNβ-1a) in patients with RMS. Safety and tolerability of teriflunomide were consistent across all studies. Objectives: To assess consistency of treatment effects based on baseline disease-modifying therapy (DMT) history in TEMSO/TOWER, and in patients switching from IFNβ-1a to teriflunomide in TENERE open-label extension. Methods: Post hoc analyses of ARR and 12week confirmed disability progression were performed in TEMSO/TOWER (n = 2251) according to patient sub-groups defined by DMT use in last 2 years (≥2 prior DMTs; 1 prior DMT; 0 prior DMT). ARR was evaluated in patients enrolled in TENE-RE extension (n = 237), including patients switching from IFNβ-1a to teriflunomide 14 mg. Results: Pooled analysis of TEMSO/TOWER data demonstrated efficacy for teriflunomide 14 mg versus placebo across prior treatment subgroups for ARR and disability progression, with no significant treatment-by-subgroup interactions. ARRs were 0.423, 0.464, and 0.303 for teriflunomide 14 mg, and 0.794, 0.641, and 0.472 for placebo for ≥2 prior DMTs, 1 prior DMT, and 0 prior DMT, respectively, representing relative risk reductions of 46.7%, 27.7%, and 35.9% for 14 mg versus placebo; correspond-ing hazard rate reductions for teriflunomide-treated patients for risk of disability progression were 78.6%, 46.6%, and 17.4%. In TENERE extension, median treatment duration ranged from 1003 to 1009 days; relapse rates were low in all groups: 0.239 (patients switching from IFNβ-1a); 0.181 (patients continuing teriflunomide 14 mg); and 0.223 (patients switching from teriflunomide 7 mg to 14 mg), and there were no significant differences between groups. Incidence of treatment-emergent adverse events was similar in all groups in TENE-RE extension. Conclusions: Analyses of pooled TEMSO/TOWER studies and TENERE extension demonstrate consistent efficacy for teriflunomide 14 mg, regardless of pretrial therapy, with treatment-naïve patients showing slightly smaller relative reductions in disability progression, reflective of lower background disease progression.

Supported by: Genzyme, a Sanofi companyDisclosure: Mark S. Freedman: Bayer HealthCare, Biogen Idec, Chugai, EMD Canada, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva Canada Innovation (consulting fees). Jerome de Seze: Genzyme (consulting fees). Tomas P. Olsson: Biogen Idec, Genzyme, Novartis (consulting fees, grant/research support); Teva (fees for non-CME services from commercial interests or their agents). Anna Czlonkowska: Bayer, Boehringer Ingelheim, Ever, Molec (consulting fees); Bayer, Ever, Genzyme, Biogen Idec, Novartis, Teva (fees for non-CME services from commercial interests or their agents); Polpharma (grant/research support). Patrick Vermersch: Biogen Idec, Genzyme, Bayer, Merck Serono (grant/research support); Biogen Idec, Genzyme, Bayer, Novartis, Merck Serono, GSK, Almirall (consulting fees). Myriam Benamor, Philippe Truffinet, Karthinathan Thangavelu: Gen-zyme, a Sanofi company (salary). Ludwig Kappos: Nothing to disclose.Keywords: Disease-modifying treatments in MS

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(DX28) 1:10,000 IS NOT ZERO: LESSONS LEARNED FROM A NATALIZUMAB-RELATED PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY CASE WITH REPEATED NEGATIVE ANTI-JC VIRUS ANTIBODY TESTINGMarie-Sarah Gagne Brosseau, Gary Stobbe, Deb Cramer, Hillary Lipe, Annette Wundes

Neurology, University of Washington, Seattle, WA

Background: Progressive multifocal leukoencephalopathy (PML) is a severe brain infection caused by the JC virus (JCV) that leads to lysis of oligodendrocytes. Natalizumab is known to be associated with PML. Clinical presentation varies; most common symptoms are cognitive impairment, weakness, and language deficit. Natalizumab-related PML has a mortality rate of 22%, and many survivors have a poor functional outcome, which makes it natalizumab’s most serious complication. 50% to 60% of adults have detectable serum antibod-ies against JCV. Seropositivity for anti-JCV antibodies is a PML risk factor, and periodic testing is recommended. Previously, two natali-zumab-treated multiple sclerosis (MS) PML patients were classified as anti-JCV antibody negative, but testing dated from 8 and 9 months before diagnosis. Objectives: To describe a case of natalizumab-associated PML in which the last anti-JCV antibody testing 2 weeks before onset of symptoms was negative. Methods: Case presenta-tion. Results: A 70-year-old woman with MS treated with natalizum-ab for 4.5 years developed PML symptoms of right-hand weakness 2 weeks after the last negative anti-JCV antibody testing. She had never received immunosuppressants. Brain magnetic resonance imaging (MRI) showed four new nonenhancing lesions suspected to be due to MS. A course of intravenous methylprednisolone for a presumed relapse was given, but her weakness worsened. Short-term repeat MRI was suggestive of PML, and CSF JCV PCR came back positive. While four prior quantitative anti-JCV antibody tests every 3 months had been negative, including 2 weeks prior to onset of symptoms (index 0.19), at time of diagnosis the result was positive (index 2.56). Evolution and management of the present case will be pre-sented. Conclusions: Initial misdiagnosis of MS relapse may delay the diagnosis of PML. Clinicians should be wary that a natalizumab-treated patient with new MRI findings and/or neurologic symptoms could have PML, including those with negative anti-JCV antibody. 2 weeks is currently the shortest interval reported between last negative anti-JCV antibody testing and onset of PML symptoms. In negative patients, risk can be due to a false-negative test result reported as 3%, or to de novo infection. In our case, de novo infection with sero-conversion is more plausible given the repeatedly negative testing. If PML is suspected, anti-JCV antibodies should be repeated even if recently negative. Moreover, short-term repeat MRI and CSF testing warrant consideration.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Disease-modifying treatments in MS, Imaging and MS, Progressive multifocal leukoencephalopathy

(DX29) ALEMTUZUMAB IMPROVES SUSTAINED ACCUMULATION OF DISABILITY OUTCOMES USING THE SAD-PLUS ASSESSMENT IN RELAPSING-REMITTING MULTIPLE SCLEROSIS PATIENTS WITH INADEQUATE EFFICACY RESPONSE TO PRIOR THERAPYGavin Giovannoni,1 Jeffrey A. Cohen,2 Hans-Peter Hartung,3 Eva Havrdova,4 David H. Margolin,5 Linda Kasten,6 Edward J. Fox7

1Queen Mary University of London, Barts and The London School of Medicine, London, United Kingdom; 2Cleveland Clinic, Cleveland, OH; 3Heinrich-Heine University, Düsseldorf, Germany; 4First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; 5Genzyme, a Sanofi company, Cambridge, MA; 6PROMETRIKA, LLC, Cambridge, MA; 7Central Texas Neurology Consultants, Round Rock, TX

Background: Alemtuzumab was more effective than subcutane-ous interferon beta-1a (SC IFNβ-1a) in reducing the risk of sustained accumulation of disability (SAD) measured with the Expanded Dis-

Background: Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing-remitting multiple sclerosis (MS). In the placebo-controlled phase 3 studies in relapsing MS, TEMSO (NCT00134563) and TOWER (NCT00751881), teriflu-nomide significantly reduced annualized relapse rate (ARR). Teriflu-nomide 14 mg also significantly reduced unique active lesions per scan in TEMSO in which magnetic resonance imaging (MRI) was performed. Objectives: To evaluate efficacy of teriflunomide in the newly diagnosed subgroup of patients from TEMSO and TOWER. Methods: Newly diagnosed patients included in this post hoc analysis of the TEMSO and TOWER studies were defined as those diagnosed with relapsing forms of MS within 1 year of enrollment and naïve to disease-modifying therapies. Treatment efficacy was evaluated by ARR (pooled analysis) and unique active lesions per scan (TEMSO only). Both outcomes were assessed using a Poisson model, with treatment, baseline Expanded Disability Status Scale strata, region, and baseline value as covariates, and study as an additional covariate in the pooled analysis. Results: In the pooled analysis, 587 newly diagnosed patients with relapsing MS were ran-domized to receive once-daily teriflunomide 14 mg (n = 183), 7 mg (n = 189), or placebo (n = 215). Relative reductions in ARR in newly diagnosed patients treated with teriflunomide versus placebo were 37.8% (95% confidence interval [CI], 10.9-56.6; P = .0096) and 24.3% (95% CI, −2.0 to 43.8; P = .0677) in the 14 mg and 7 mg groups, respectively. The respective ARRs were 0.270, 0.328, and 0.433 in the 14 mg, 7 mg, and placebo groups. In TEMSO, relative reduction in number of unique active lesions per scan versus placebo group (n = 99) was 64.6% (95% CI, 33.6-81.2; P = .0012) in the 14 mg group (n = 80) and 47.3% (95% CI, 22.2-64.3; P = .0013) in the 7 mg group (n = 88). MRI endpoints were not evaluated in TOWER. Conclusions: Consistent with results from individual tri-als, pooled data from TEMSO and TOWER demonstrated significant reductions in ARR in newly diagnosed patients with MS treated with teriflunomide 14 mg. Additionally, significant reductions in the number of unique active lesions were observed in newly diagnosed patients in TEMSO. Together with the results of the TOPIC study (NCT00622700) in patients with a first clinical episode suggestive of MS, this post hoc analysis supports a consistent positive effect of teriflunomide on clinical and MRI measures early in the disease.

Supported by: Genzyme, a Sanofi companyDisclosure: Jerry S. Wolinsky: AbbVie, Actelion, Alkermes, Athersys, Inc, EMD Serono, Forward Pharma, Genentech, Genzyme, Novartis, Roche, Teva, Teva Neurosciences, to-BBB, XenoPort (consulting fees); Genzyme, Sanofi, National Institutes of Health, National Multiple Sclerosis Society (grant/research support); Chemicon International (royalty). Mark S. Freedman: Bayer HealthCare, Biogen Idec, Chugai, EMD Canada, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva Canada Innovation (consulting fees). Giancarlo Comi: Almirall, Bayer, Biogen, Excemed, Genzyme, Merck Serono, Novartis, Receptos, Sanofi, Serono Symposia International Foundation, Teva (fees for non-CME services from com-mercial interests or their agents); Almirall, Bayer, Chugai, Excemed, Genzyme, Merck Serono, Novartis, Receptos, Sanofi, Serono Symposia International Foun-dation, Teva (consulting fees). Jean-Pierre Bouchard: Biogen Idec, EDM Serono, Roche, Sanofi-Aventis, Novartis, Teva Canada (consulting fees). Biogen Idec, EDM Serono, Sanofi-Aventis, Novartis (grant/research support). Ludwig Kappos: Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi-Aventis, Santhera, Siemens, Teva, UCB, XenoPort (consulting fees); Bayer HealthCare, Biogen Idec, Merck, Novartis, Roche, Swiss MS Society, Swiss National Research Foundation, European Union, Roche Research Foundations (grant/research support); Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva (support of educational activities); Neurostatus Systems GmbH (royalty); Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi-Aventis, Teva (speaker fees, fees for non-CME services from commercial interests or their agents). Philippe Truffinet, Steven Cavalier: Genzyme, a Sanofi company (salary); Sanofi (owner-ship interest). Karthinathan Thangavelu: Genzyme, a Sanofi company (salary). Paul O’Connor: Actelion, Bayer, Biogen Idec, BioMS, Cognosci, Daiichi Sankyo, EMD Serono, Genentech, Genmab, Novartis, Roche, Sanofi-Aventis, Teva (con-sulting fees, grant/research support).Keywords: Disease-modifying treatments in MS

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TION. Methods: An interim analysis for patients who received continuous DAC HYP 150 mg treatment was performed on January 20, 2014 (data cutoff date). Safety was evaluated for all patients enrolled. Descriptive statistics are reported. Results: The SELECTED study enrolled 90% (N = 410) of patients who completed SELEC-TION. In a subgroup of 94 patients continuously treated with DAC HYP 150 mg for 3 years, the adjusted annualized relapse rate (95% confidence interval [CI]) analyzed at 6-month intervals was 0.089 (0.033-0.244) for weeks >96–120 and 0.047 (0.012-0.187) for weeks >120–144. In year 3, the adjusted mean (95% CI) number of new or newly enlarging T2-hyperintense lesions was 0.56 (0.24-1.32) and the mean (median) annualized change in brain volume was −0.3% (−0.3%). In the overall safety analysis (N = 410), medi-an treatment time was 25 months (range 0–45; 854 patient-years). Adverse events (AEs) were reported in 76% of patients, serious AEs excluding MS relapse in 16%, treatment discontinuation due to AEs in 12%, study withdrawal due to AEs in 11%. AEs were mainly mild to moderate in severity, and the most common AEs (≥10%) were MS relapse (22%), nasopharyngitis (12%), and upper respiratory tract infection (12%). Most commonly reported SAEs (in ≥3 patients) included MS relapse (11%) and ulcerative colitis, increased hepatic enzyme, pneumonia, and urinary tract infection (<1% each). The incidence of AEs, SAEs, and treatment-related study discontinuations did not increase over time, and no deaths were reported. Conclu-sions: The efficacy of daclizumab HYP on clinical and radiologic outcomes was sustained over 3 years. The safety profile of DAC HYP was stable with extended duration of therapy into the third year of treatment in SELECTED.

Supported by: Biogen Idec, AbbVie Biotherapeutics, IncDisclosure: Ralf Gold: Biogen, Teva, Sanofi, Novartis, Bayer, Merck Serono (consulting fees). Gavin Giovannoni: Merck Serono, Biogen Idec, Vertex Phar-maceuticals, Bayer Schering Pharma, Pfizer Inc, Teva Pharmaceutical Industries Ltd, Sanofi (consulting fees). Krzysztof W. Selmaj: Biogen Idec (fees for non-CME services from commercial interests or their agents); Genzyme, Novartis, Ono, Roche, Synthon, Teva (consulting fees). Eva Havrdova: Bayer Schering Health-care, Biogen Idec, Sanofi Genzyme, Merck Serono, Novartis, Teva (consulting fees); Biogen Idec (grant/research support). Ernst-Wilhelm Radue: Actelion, Basilea, Bayer Schering, Biogen Idec, Merck Serono, Novartis (consulting fees). Till Sprenger: Novartis Switzerland (grant/research support); Novartis, Actelion, ATI, Electrocore, Teva, Genzyme, Biogen Idec (consulting fees). Dusan Stefoski: Biogen Idec, Acorda, Teva Neuroscience, EMD Serono, Elan (consulting fees). Xavier Montalbán: Actelion, Almirall, Bayer, Biogen Idec, Genzyme, Merck, Neurotec, Novartis, Octapharma, Receptos, Roche, Sanofi, Teva, Trophos (con-sulting fees). Yaoshi Wu, Gulden Ozen, Mark Beatty, Jacob Elkins: Biogen Idec (ownership interest, salary). Steven J. Greenberg: AbbVie Biotherapeutics Inc (ownership interest, salary).Keywords: Daclizumab HYP, Disease-modifying treatments in MS

(DX31) SLEEP DISORDER IN PATIENTS WITH MULTIPLE SCLEROSISDaymet D. Grass

Ciren, Havana, Cuba

Background: Multiple sclerosis (MS) is a neurologic disease that usually presents in young adults; its origin is unknown. It is the second-leading cause of disability, following car accidents. Usually people with MS do not complain of sleep disorders, but they may do so when asked. Sleep disorders may be up to three times more frequent in MS patients than in the rest of the population. Patients may have more daytime sleepiness, increased sleep latency, and nighttime awakenings. A therapeutic alternative for MS patients is the use of interferon beta-1a (IFNβ-1a; Rebif) 44 µg. Objectives: Assess sleep status in patients with MS treated with IFNβ-1a using scales and questionnaires. Methods: We selected 88 patients with a diagnosis of MS and administered various scales and question-naires including the Epworth scale and insomnia medical instrument. Results: Preliminary survey results revealed no significant sleep disorders in these patients. Conclusions: Patients with MS under treatment with IFNβ-1a (Rebif) 44 µg have a range of sleep disorder

ability Status Scale (EDSS) in CARE-MS II (NCT00548405). But EDSS alone may not be sensitive enough to detect meaningful changes in neurologic function in some relapsing-remitting multiple sclerosis (MS) patients. Here, we present a novel composite endpoint that uses the EDSS, components of the MS Functional Composite, and the Sloan low-contrast visual acuity test to reexamine disability accumulation in CARE-MS II. Objectives: To examine alemtuzumab efficacy on SAD outcomes, as evaluated by the composite SAD-plus assessment, in the CARE-MS II study. Methods: Patients who participated in the 2-year, randomized, rater-blinded CARE-MS II study had active relapsing MS and ≥1 relapse on prior disease-modifying therapy. Patients received alemtuzumab 12 mg/day via intravenous infusions on 5 consecutive days at baseline and 3 consecutive days at month 12, or SC IFNβ-1a 44 µg 3 times/week. SAD was defined as ≥1.0-point increase in EDSS score sustained over 6 months (≥1.5 point in patients with a baseline EDSS = 0). Post hoc disability outcomes included the proportion of patients with worsening on the following measures sus-tained over 6 months: Timed 25-Foot Walk (T25FW; 20% increase from baseline), 9-Hole Peg Test (9-HPT; 20% increase from baseline), and Sloan visual acuity at 2.5% contrast (7-letter worsening). The proportion of patients with sustained worsening on any disability measure (T25FW, 9-HPT, Sloan, or SAD) was also assessed (SAD-plus endpoint). Results: Compared with SC IFNβ-1a (n = 202), alemtuzumab treatment (n = 435) led to significantly fewer patients with SAD (12.7% vs. 21.1%; P = .0084), or sustained worsening on T25FW (10.6% vs. 16.7%; P = .0401), 9-HPT (5.4% vs. 10%; P = .0450), or Sloan (9.8% vs. 18.2%; P = .0068). The proportion of patients achieving the SAD-plus endpoint was significantly reduced by 37% with alemtuzumab versus SC IFNβ-1a (33.6% vs. 47.8%; P = .0013). Conclusions: Alemtuzumab treatment was superior in reducing disability progression compared with SC IFNβ-1a as mea-sured by the SAD-plus composite endpoint encompassing EDSS-based SAD as well as ambulation, upper-limb dexterity, and visual impairment. The SAD-plus endpoint is more sensitive to clinically meaningful impairments than EDSS-based SAD alone.

Supported by: Genzyme, a Sanofi company; Bayer HealthCare PharmaceuticalsDisclosure: Gavin Giovannoni: AbbVie, Biogen Idec, Genzyme, Glaxo-SmithKline, Merck, Merck-Serono, Novartis, Roche, Sanofi, Synthon BV, Teva (consulting fees). Jeffrey A. Cohen: EMD Serono, Genentech, Innate Immuno-therapeutics, Vaccinex (consulting fees). Hans-Peter Hartung: Bayer HealthCare, Biogen Idec, CSL Behring, Genzyme, Hoffmann-LaRoche, Novartis, Octaphar-ma, Sanofi, Teva (consulting fees). Eva Havrdova: Biogen Idec, Genzyme, Merck, Novartis, Receptos (consulting fees); Biogen Idec (grant/research support). David H. Margolin: Genzyme, a Sanofi company (salary). Linda Kasten: Genzyme, a Sanofi company (consulting fees). Edward J. Fox: Bayer HealthCare, Biogen Idec, Eli Lilly, EMD Serono, Genzyme, Novartis, Ono, Opexa Therapeutics, Pfizer, Sanofi, Teva (consulting fees, grant/research support, honoraria, travel support).Keywords: Alemtuzumab, Disease-modifying treatments in MS

(DX30) LONG-TERM EFFICACY AND SAFETY OF DACLIZUMAB HIGH-YIELD PROCESS IN RELAPSING-REMITTING MULTIPLE SCLEROSIS: RESULTS FROM THE SELECTED EXTENSION STUDYRalf Gold,1 Gavin Giovannoni,2 Krzysztof W. Selmaj,3 Eva Havrdova,4 Ernst-Wilhelm Radue,5 Till Sprenger,5 Dusan Stefoski,6 Xavier Montalbán,7 Yaoshi Wu,8 Steven J. Greenberg,9 Gulden Ozen,8 Mark Beatty,8 Jacob Elkins8

1St. Josef Hospital, Ruhr University, Bochum, Germany; 2Queen Mary University of London, Barts and The London School of Medicine, London, United Kingdom; 3Medical University of Lodz, Lodz, Poland; 4Charles University in Prague, Prague, Czech Republic; 5Medical Image Analysis Center, University Hospital Basel, Basel, Switzerland; 6Rush University Medical Center, Chicago, IL; 7Hospital Universitari Vall d’Hebron, Barcelona, Spain; 8Biogen Idec, Cambridge, MA; 9AbbVie Biotherapeutics Inc, Redwood City, CA

Background: Daclizumab high-yield process (DAC HYP) is a monoclonal antibody against CD25 that modulates IL-2 signaling. Its safety and efficacy over 2 years of treatment have previously been reported in the SELECTION trial. Objectives: To evaluate the long-term safety and efficacy of DAC HYP 150 mg subcutaneous (SC) every 4 weeks in patients with relapsing-remitting multiple sclerosis (RRMS) who previously completed up to 2 years’ treatment in SELEC-

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Keywords: Disease-modifying treatments in MS, Epidemiology of MS, Immunol-ogy and MS

(DX33) RETROSPECTIVE ANALYSIS OF THE TREATMENT OF RELAPSING-REMITTING MULTIPLE SCLEROSIS WITH FINGOLIMOD AT THE DEPARTMENT OF NEUROLOGY, BON SECOURS HOSPITAL TRALEE, IRELANDMoira P. Hayes, Helena Moore

Neurology, Bon Secours Hospital Tralee, Tralee, Kerry, Ireland

Background: Multiple sclerosis (MS) is a chronic, progressive immune-mediated disease of the central nervous system. It is char-acterized by multifocal demyelination, inflammation, and axonal degeneration. The most common presentation of MS is a relapsing-remitting course, which is characterized by acute, disabling attacks followed by a period in which symptoms completely or partially abate. Fingolimod (Gilenya) is a once-daily oral treatment that has been approved for the treatment of relapsing-remitting MS in Ireland since July 2012. It is a functional sphingosine 1-phosphate receptor antagonist that acts to sequester potentially pathogenic T cells within the secondary lymphoid organs, thereby preventing their infiltra-tion into the CNS, and thus significantly reduces relapse rate and disability progression in patients. Upon initiation of the first dose of fingolimod, patients must undergo a 6-hour observation period, as fingolimod treatment can result in an initial and transient decrease in heart rate. Objectives: Here we describe our experience with the first 30 patients who received fingolimod as a treatment for relapsing-remitting MS (RRMS) at the Neurology Department in Bon Secours Hospital in Tralee, Ireland. Methods: Single-center retro-spective study evaluating baseline characteristics, heart rate at first dose, and confirmed relapses since initiation in the first 30 patients for whom fingolimod was prescribed since approval. Results: The mean patient age on initiation of fingolimod therapy was 42.4 ± 9.3 years, and the mean duration of disease was 8.2 ± 3.7 years. As expected, the majority of the patient cohort was female. Prior therapies included interferon beta-1a and -1b, glatiramer acetate, and natalizumab. As of December 2014, the mean duration of ongoing fingolimod therapy was 22.6 ± 8.5 months. In these 30 patients we found that the mean heart rate decreased by 10% follow-ing first dose, and the effect was maximal at 4 hours. One patient, with a baseline heart rate of 59 bpm, experienced a second-degree atrioventricular block and sustained bradycardia following initial dosing with fingolimod. This patient was successfully treated with an isoprenaline infusion, discharged, and continued on treatment with no further cardiac events. Since initiation of fingolimod, 93% of the 30 patients have remained free from clinically confirmed relapses. However, there have been three discontinuations to date, due to known fingolimod side effects of raised liver enzymes, lymphopenia, and macular edema. Conclusions: In summary, our experience in treating patients with RRMS with fingolimod has been generally consistent with results obtained previously in randomized controlled clinical trials.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Disease-modifying treatments in MS

(DX34) PATIENT EXPERIENCE AND TOLERANCE OF NEW GLATIRAMIR DOSINGLynda R. Hillman,1 Kathy Burgess,2 Wendy Miller2

1MS Center of Excellence, West, VA Puget Sound Healthcare, Seattle, WA; 2Rehab Care Services, VA Puget Sound Healthcare, Seattle, WA

Background: Multiple sclerosis (MS) disease-modifying thera-pies (DMTs) have enabled many patients to benefit from reduced relapses, slower disease progression, and fewer brain lesions than experienced by patients not on DMTs. The number of new DMT options, both oral and injection or intravenous, has expanded in recent years. This is welcome news for both providers and people living with MS. However, even the most efficacious DMT will not help

severity; however, preliminary study results reveal no significant sleep disorder in these patients.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Complementary/alternative therapies in MS, MS and the caregiver/family, Nursing management in MS

(DX32) BASELINE DEMOGRAPHICS AND DISEASE CHARACTERISTICS FROM OPERA PHASE 3 TRIALS EVALUATING OCRELIZUMAB IN PATIENTS WITH RELAPSING MULTIPLE SCLEROSISStephen L. Hauser,1 Giancarlo Comi,2 Hans-Peter Hartung,3 Fred D. Lublin,4 Krzysztof W. Selmaj,5 Anthony Traboulsee,6 Amit Bar-Or,7 Douglas L. Arnold,8 Gaelle Klingelschmitt,9 David Leppert,9 Algirdas Kakarieka,9 Hideki Garren,9 Ludwig Kappos10

1Department of Neurology, University of California, San Francisco, CA; 2University Vita-Salute San Raffaele, Milan, Italy; 3Heinrich-Heine University, Düsseldorf, Germany; 4The Icahn School of Medicine at Mount Sinai, New York, NY; 5Medical University of Lodz, Lodz, Poland; 6University of British Columbia, Vancouver, BC, Canada; 7Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada; 8Montreal Neurological Institute, McGill University, Montreal, QC, Canada; 9Global Medical Affairs, Neuroscience, F. Hoffmann La-Roche/Genentech, Basel, Switzerland; 10University Hospital Basel, Basel, Switzerland

Background: Ocrelizumab (OCR) is a recombinant humanized monoclonal antibody that selectively targets CD20+ B cells. Two phase 3 trials, OPERA I and II, are investigating the efficacy and safety of OCR compared with interferon beta (IFNβ) in patients with relapsing multiple sclerosis (RMS). Objectives: To present demo-graphic and baseline disease characteristics of patients in the OPERA I and II studies. Methods: The OPERA trials are randomized, double-blinded, double-dummy, parallel-group studies investigating the efficacy and safety of 600 mg OCR administered by intravenous infusion every 24 weeks compared with high-dose, high-frequency IFNβ-1a (44 µg 3 times per week). Patients were randomized (1:1) to OCR or IFNβ. Entry criteria included a diagnosis of RMS (McDon-ald criteria, 2010), Expanded Disability Status Scale (EDSS) score of 0 to 5.5, and age of 18 to 55 years. At least two documented relapses within the last 2 years or one relapse in the last 1 year prior to screening were required. The primary endpoint is the annualized relapse rate at 2 years. Results: A total of 821 and 835 patients were randomized in OPERA I and II, respectively. Mean baseline age was 37.0 and 37.3 years, respectively, in OPERA I and II; 66.0% of patients were female. Patients had symptoms of MS for a mean duration of 6.5 years in OPERA I and 6.7 years in OPERA II. The mean EDSS score was 2.80 in OPERA I and 2.82 in OPERA II. The mean number of gadolinium-enhancing (Gd+) lesions on brain MRI was 1.79, with 59.7% of patients with no Gd+ lesions in OPERA I, and 1.87 and 59.8%, respectively, in OPERA II. Conclu-sions: The OPERA I and II baseline data are consistent with an RMS population. The results of the OPERA studies will provide information on the efficacy and safety of ocrelizumab compared with IFNβ in RMS.

Supported by: F. Hoffmann-La Roche; Genzyme, a Sanofi company; Bayer HealthCare Pharmaceuticals

Disclosure: Stephen L. Hauser, Fred D. Lublin, Amit Bar-Or, Douglas L. Arnold: F. Hoffmann-La Roche (grant/research support). Giancarlo Comi: Almirall, Bayer, Biogen, Excemed, Genzyme, Merck Serono, Novartis, Receptos, Sanofi, Serono Symposia International Foundation, Teva (fees for non-CME services from commercial interests or their agents); Almirall, Bayer, Chugai, Excemed, Genzyme, Merck Serono, Novartis, Receptos, Sanofi, Serono Symposia International Foundation, Teva (consulting fees). Hans-Peter Hartung: Bayer HealthCare, Biogen Idec, CSL Behring, Genzyme, Hoffmann-LaRoche, Novar-tis, Octapharma, Sanofi, Teva (consulting fees). Krzysztof W. Selmaj: Biogen Idec, Inc (fees for non-CME services from commercial interests or their agents); Genzyme, Novartis, Ono, Roche, Synthon, Teva (consulting fees). Anthony Traboulsee: Biogen, Chugai, Genzyme, MedImmune, Novartis, Roche, Serono, Teva Innovation (consulting fees); Genzyme, Roche (grant/research support). Gaelle Klingelschmitt, David Leppert, Algirdas Kakarieka, Hideki Garren: F. Hoffmann-La Roche (salary). Ludwig Kappos: Nothing to disclose.

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dose or most doses by 69% (20/29) of responders during 0–3 months of therapy versus 45% (13/29) after >3 months. 97% of responders agreed that for most patients these side effects have only mild to moderate (FLS) or minimal (ISR) impact on activities of daily living during the first 3 months of treatment. Conclusions: Survey responders indicated that the frequency and duration of FLS and ISR generally declined after 3 months’ treatment and they had minimal to moderate impact on activities of daily living. Overall, these results reflect substantive experience with peginterferon beta-1a and may have an impact on patient adherence to therapy and ultimately influ-ence patient outcomes.

Supported by: Biogen IdecDisclosure: DeRen Huang: Teva, Biogen Idec (consulting fees). Diego Centonze: Almirall, Bayer Schering, Biogen Idec, Genzyme, GW Pharmaceuticals, Merck Serono, Novartis, Sanofi-Aventis, Teva (consulting fees); Bayer Schering, Biogen Idec, Novartis, Merck Serono, Sanofi-Aventis, Teva (grant/research support). June Halper: Biogen Idec (fees for non-CME services from commercial interests or their agents). Scott D. Newsome: Biogen Idec, Novartis (grant/research support); Biogen Idec, Genzyme, Novartis (consulting fees). Christopher Robertson, Vladimir Evil-evitch: Biogen Idec (ownership interest, salary). Xiaojun You, Guido Sabatella, Leslie Leahy: Biogen Idec (salary).Keywords: Disease-modifying treatments in MS, Management of activities of daily living in MS, Peginterferon

(DX36) USER TRIAL QUESTIONNAIRE AND QUALITY OF LIFE RESPONSES IN PATIENTS WITH MULTIPLE SCLEROSIS BY NEUROLOGIC AND COGNITIVE STATUS: MOSAIC STUDYBruce L. Hughes,1 Jonathan Calkwood,2 Brooke Hayward,3 Fernando Dangond3

1Ruan Multiple Sclerosis Center, Des Moines, IA; 2Schapiro Center for Multiple Sclerosis, Minneapolis Clinic of Neurology, Golden Valley, MN; 3EMD Serono, Inc, Rockland, MA

Background: The 12-week, phase 3b, open-label, single-arm MOSAIC study (NCT00958009) evaluated the Rebidose single-use autoinjector (SA) for self-injection of 44 µg subcutaneous interferon beta-1a (IFNβ-1a SC) three times weekly in 109 relapsing multiple sclerosis (RMS) patients. Objectives: Evaluate patient-reported acceptability, satisfaction, and quality of life (QOL) perception fol-lowing 12 weeks of SA use between patients enrolled in MOSAIC with non-normal and normal status, as determined by neurologic and cognitive assessments at baseline (BL). Methods: Prespecified analy-ses compared patient perception of the SA using a 25-item User Trial Questionnaire (UTQ; range –50 to 50) administered after initial dose and at 6 and 12 weeks. Comparisons were made between patients with non-normal and normal status for 15 neurocognitive subtypes (eg, visual, mental, physical, memory). QOL change was analyzed using paired t tests in intent-to-treat (ITT) patients and in subgroups with non-normal status using the 36-item Short Form Health Status Survey (SF-36) assessment at BL and week 12. Results: Mean age of the ITT population was 6.0 ± 9.3 years; 86.2% were white, and 69.7% were female. Week 12 UTQ score was significantly different between normal and non-normal status patients for three neurocogni-tive subtypes: patients with “impaired extraocular movement” (n = 10) and “dominant hand abnormality” (n = 38) were less positive (scores decreased from 46.7 to 25.5 and 44.4 to 27.8, respec-tively), and patients with non-normal “sensory status” (n = 15) were more positive with use of the SA than patients with normal status (score increased from 23.0 to 49.2). There were no significant differ-ences between patients with non-normal and normal dominant hand status for the individual UTQ items. Patients indicated that they would continue to use the SA after the study (100% and 98.6% for non-normal and normal status, respectively). QOL, as measured by SF-36 in ITT patients, increased significantly (P = .04) from screening to week 12 for the domain assessing physical health (role-physical). Sig-nificant improvements from BL to week 12 were observed for SF-36 domains in subgroups with non-normal memory (n = 83, role-physi-cal, P = .02; role-emotional, P = .04) and with non-normal executive function (n = 82, role-physical, P = .03; physical health component, P = .04). Conclusions: After 12 weeks of SA use for IFNβ-1a SC self-injection, RMS patients were satisfied overall, would continue using

patients if adherence is problematic or intolerable due to DMT side effects. Clinical trials may not show the extent of tolerability problems with a new DMT—only postmarket experience shows the full array of adverse effects. We describe the experience and tolerance of a new form of glatiramir acetate in a population of veterans with MS in Washington state. Glatiramir, a first-line DMT, was originally approved in a 20-mg dose given by daily subcutaneous injection. In 2013, the FDA approved a 40-mg dose of glatiramir that required only 3 subcutaneous injections per week—a reduction of over 50% in injection frequency from the original 7 per week regimen. It was expected that patients with MS would welcome an option that required fewer injections and find it well tolerated. Objectives: 1) To understand and describe the patient experience of adherence to the 3 times weekly glatiramir. 2) To identify both positive and trouble-some aspects of this DMT regimen, in order to intervene and manage problems that otherwise might cause patients to self-discontinue DMT. 3) To further analyze this patient-reported data for elements crucial to patient satisfaction and quality improvement. Findings will be used as we evaluate current and potential programs in order to further improve care of veterans with MS. Methods: Chart reviews of veterans with MS taking glatiramir; may also include focus groups of these veterans taking glatiramir. Results: Initial findings indicate that approximately 25% of patients find the 40-mg dose less tolerable than the 20-mg dose. Increased injection-site reactions are reported. More concerning is the incidence, although small, of systemic reac-tions. Data collection continues through late April/early May 2015. Conclusions: In progress.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Disease-modifying treatments in MS, Nursing management in MS, Tolerability of DMT

(DX35) EVALUATION OF PEGINTERFERON BETA-1A TOLERABILITY PROFILE: GAINING CONSENSUS USING THE DELPHI TECHNIQUEDeRen Huang,1 Diego Centonze,2 June Halper,3 Scott D. Newsome,4 Christopher Robertson,5 Xiaojun You,5 Guido Sabatella,5 Vladimir Evilevitch,5 Leslie Leahy5

1Neurology and Neuroscience Associates, Akron, OH; 2Multiple Sclerosis Clinical Center, Policlinico Universitario Tor Vergata, Rome, Italy; 3Consortium of Multiple Sclerosis Centers, Hackensack, NJ; 4Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD; 5Biogen Idec Inc, Cambridge, MA

Background: ADVANCE was a 2-year, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of subcu-taneous peginterferon beta-1a 125 µg given every 2 or 4 weeks in patients with multiple sclerosis (MS). Objectives: To understand and characterize peginterferon beta-1a treatment-related flu-like symptoms (FLS) and injection-site reactions (ISR) in patients with MS based on experiences in the ADVANCE study. Methods: ADVANCE investiga-tors with ≥2 enrolled patients in the United States and ≥10 elsewhere were offered the opportunity to participate in a consensus-generating process based on the Delphi methodology. The development of two questionnaires was overseen by an independent steering committee (N = 4). Questionnaire 1 (150 questions) was designed to better understand frequency, impact, and management of FLS and ISR in MS patients treated with peginterferon beta-1a. After completion of the first questionnaire, questionnaire 2 (15 questions) was designed to clarify best practices and generate consensus recommendations for the management of these side effects. Results: Of the 84 investiga-tors who met inclusion criteria, 50 agreed to participate; 30 com-pleted questionnaire 1 and 29 completed questionnaire 2. The 30 participating investigators represented 374 patients from ADVANCE. 93% (28/30) of responders reported FLS and 97% (29/30) reported ISR in ≥1 of their patients. FLS were reported in a typical patient after every dose or most doses by 71% (20/28) of responders during 0–3 months of therapy versus 39% (11/28) of responders after >3 months of therapy. 90% (26/29) of responders agreed that flu-like symptoms generally last ≤24 hours following peginterferon beta-1a administration. ISR were reported in a typical patient after every

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CO; 4Psychiatry, University of Colorado, Aurora, CO; 53:1 Neuropsychology Consultants, PLLC, Minneapolis, MN

Background: Pediatric multiple sclerosis (MS) is an immune-mediat-ed disease of the central nervous system (CNS) that has been increas-ingly recognized. Clinical disease factors including clinical and radiologic results vary substantially from those in adult MS. Pediatric MS patients present unique care management challenges due to the effect of a neurodegenerative disease on a developing brain. Previ-ous literature highlighting the suboptimal correlation between clinical symptomology and magnetic resonance imaging (MRI) results has led to the recognition of a “clinical-radiographic paradox.” Collabora-tive care through interdisciplinary teams is vital to the management of pediatric MS. Objectives: We present an update on a longitudinal case study of a pediatric patient with MS including neuroimaging and neuropsychological findings. Methods: Results from surveil-lance MRI scans and neuropsychological assessments completed for a patient with a pediatric diagnosis of MS over the span of 5 years are presented. These results are considered within the context of highly effective disease-modifying therapy. Results: Surveillance MRI results revealed stable lesions, without evidence of disease progression. Despite stable neuroimaging results, data from repeat neuropsychological evaluations revealed declines on measures of working memory, processing speed, verbal fluency, and vocabulary knowledge between the first two neuropsychological evaluations. Weaknesses in aspects of academic fluency and executive function-ing were also noted. These declines were seen within the context of stable intellectual abilities, visual-motor integration, verbal learning and memory, and attention skills. Conclusions: This case highlights the complex neurodegenerative aspects of MS and the value of interdisciplinary monitoring for disease progression in pediatric MS. Commonly used T2-weighted sequences are insensitive to cortical demyelination and damage to gray-matter structures, which may affect cognitive functioning in MS. Cognitive dysfunction has specific implications in the care management of pediatric patients with MS. For these reasons, routine neuropsychological assessments should be conducted to monitor functioning and assist with medical, educa-tional, and psychosocial interventions.

Disclosure: Christa Hutaff-Lee, Angela Canas, Jennifer Lindwall, Kendra Bjoraker: Nothing to disclose. Teri Schreiner: National Multiple Sclerosis Society (grant/research support).Keywords: Comprehensive care and MS, Neuropsychology and MS, Psychological issues and MS

(DX39) INFUSION-ASSOCIATED REACTIONS IN PATIENTS RECEIVING ALEMTUZUMAB AFTER SWITCHING FROM SUBCUTANEOUS INTERFERON BETA-1ACarolina Ionete,1 Jeffrey A. Cohen,2 Edward J. Fox,3 Hans-Peter Hartung,4 Eva Havrdova,5 Krzysztof W. Selmaj,6 David H. Margolin,7 Linda Kasten,8 D. Alastair S. Compston9

1University of Massachusetts Memorial Medical Center, Worcester, MA; 2Cleveland Clinic, Cleveland, OH; 3Central Texas Neurology Consultants, Round Rock, TX; 4Heinrich-Heine University, Düsseldorf, Germany; 5First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; 6Medical University of Lodz, Lodz, Poland; 7Genzyme, a Sanofi company, Cambridge, MA; 8PROMETRIKA, LLC, Cambridge, MA; 9University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom

Background: Alemtuzumab is a humanized anti-CD52 anti-body approved for the treatment of relapsing forms of multiple sclerosis (MS). In the CARE-MS I (NCT00530348) and CARE-MS II (NCT00548405) studies, infusion-associated reactions (IARs) occurred in most patients but were predominantly nonserious and effectively managed. Objectives: To assess the incidence of IARs in patients who received alemtuzumab in an extension study (NCT00930553) after receiving subcutaneous interferon beta-1a (SC IFNβ-1a) in either of the CARE-MS core studies.Methods: The phase 3 CARE-MS I and II studies compared SC IFNβ-1a (44 µg 3 times per week) with alemtuzumab (12 mg/day on 5 consecutive days at baseline and on 3 consecutive days at month 12) in patients with active relapsing MS. In the extension study, patients previously receiving SC IFNβ-1a were switched to alemtu-

the SA, and reported improvement in QOL despite some degree of neurologic or cognitive impairment.

Supported by: EMD Serono, Inc, a subsidiary of Merck KGaA; Pfizer IncDisclosure: Bruce L. Hughes: EMD Serono, Pfizer, Biogen Idec, Bayer, Gen-zyme, Novartis, Teva, Acorda (consulting fees, grant/research support, speakers’ bureau). Jonathan Calkwood: Acorda, Bayer HealthCare, Biogen Idec, EMD Serono, Genzyme, Novartis, Questcor, Teva (speakers’ bureau and/or advisory board); Biogen Idec, Novartis, Roche (grant/research support). Brooke Hayward, Fernando Dangond: EMD Serono, Inc, a subsidiary of Merck KGaA (salary).Keywords: Disease-modifying treatments in MS, Equipment in MS, Psychologi-cal issues and MS

(DX37) SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF ALKS 8700, A NOVEL ORAL THERAPY FOR RELAPSING-REMITTING MULTIPLE SCLEROSIS, IN HEALTHY SUBJECTSThomas L. Hunt,1 Chandra Durairaj,2 Richard Leigh-Pemberton,2 Ying Jiang,2 Joan Manthis,2 Marjie Hard2

1PPD Development, Austin, TX; 2Alkermes, Inc, Waltham, MA

Background: ALKS 8700 is an aminoethyl ester of monomethyl fumarate (MMF) that undergoes hydrolysis through esterases to produce MMF that is being developed for the treatment of relapsing-remitting multiple sclerosis (RRMS). Objectives: To evaluate the safety, tolerability, and pharmacokinetics following single oral administration of ALKS 8700 and its comparison to an approved drug product, dimethyl fumarate (DMF). Methods: This phase 1, randomized, double-blind, placebo-controlled study was conducted in two parts. Part 1 was a sequential, single-ascending dose design in healthy subjects with 7 cohorts. In each cohort, 6 subjects received a single oral dose of ALKS 8700 and 2 subjects received placebo (8 subjects/cohort). Part 2 was a two-treatment, two-period, cross-over design with a washout period of 7 days and two active treatment sequences. In each period, 6 subjects received a single dose of either ALKS 8700 or 240 mg DMF and 4 subjects received placebo. Results: All randomized subjects completed the study. In Part 1, doses of ALKS 8700 ranging from 49 mg to 980 mg were evalu-ated. ALKS 8700 was not detected in plasma as a result of being rapidly converted to MMF. MMF exposure increased with increasing ALKS 8700 dose levels. The ALKS 8700 dose selected for Part 2 was 420 mg. The Cmax of MMF after treatment with ALKS 8700 was 34% lower than after treatment with DMF, while AUC was comparable between both treatments. The median lag time for absorption was longer in subjects treated with ALKS 8700 compared to DMF (1.5 hour vs. 0.5 hour, respectively). ALKS 8700 treatment resulted in less variability in MMF exposure than DMF. Throughout the study, all dose levels of ALKS 8700 were generally well tolerated. The most common adverse events (AEs) were flushing and gastrointestinal (GI)-related (for both ALKS 8700 and DMF); all AEs were mild or moderate in severity. In Part 2, the percentage of subjects with GI-related AEs was notably lower for ALKS 8700 (8.3%) compared to DMF (41.7%). No serious AEs or discontinuations due to AEs were observed. Conclu-sions: ALKS 8700 treatment was well tolerated and provided MMF exposure comparable to DMF. Less variability in Cmax and AUC and lower rates of GI-related AEs were observed following treatment with ALKS 8700 compared to DMF. The results of this study support further clinical investigation of ALKS 8700 for the treatment of RRMS.

Supported by: Alkermes, IncDisclosure: Thomas L. Hunt: Nothing to disclose. Chandra Durairaj, Richard Leigh-Pemberton, Ying Jiang, Joan Manthis, Marjie Hard: Alkermes, Inc (salary).Keywords: Disease-modifying treatments in MS, Monomethyl fumarate

(DX38) THE IMPORTANCE OF INTERDISCIPLINARY MONITORING FOR DISEASE PROGRESSION IN PEDIATRIC MULTIPLE SCLEROSISChrista Hutaff-Lee,1,2 Angela Canas,1,2 Jennifer Lindwall,3,4 Kendra Bjoraker,5 Teri Schreiner1,2

1Pediatrics, University of Colorado, Aurora, CO; 2Neurology, Children’s Hospital Colorado, Aurora, CO; 3Psychiatry and Behavioral Sciences, Children’s Hospital Colorado, Aurora,

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(decreased: 17.7% vs. 5.8%; stable: 67.5% vs. 50.3%; increased: 14.8% vs. 40.3%). In the overall population, increased LV was associated with worsening disability at month 24 (LV decreased; stable; increased: changes in EDSS score [−0.01; −0.01; 0.14] and MSFC score [0.08; 0.01; −0.08]; and proportions with 3-month CDP [16.4%; 17.4%; 21.7%] and 6-month CDP [11.3%; 14.0%; 19.0%]). The results within the fingolimod and placebo groups were consistent with this overall pattern, and LV in the first 2 years was similarly associated with disability at month 48. Conclusions: Categorical change in T2 LV in the first 2 years was associated with disability at months 24 and 48 in patients with RRMS. Patients with increased T2 LV exhibited higher mean changes in EDSS and MSFC scores and a shorter time to CDP. Fewer patients receiving fingolimod had increased T2 LV, and higher proportions demonstrated stable or decreased LV, compared with those receiving placebo.

Supported by: Novartis Pharmaceuticals CorporationDisclosure: Douglas Jeffery: Bayer, Biogen Idec, Teva Pharmaceuticals, Serono, Pfizer, Glaxo, Novartis Pharmaceuticals Corporation, Acorda Therapeutics, Genzyme, XenoPort, Alkermes, QuestCor (consulting fees). Elisabetta Verdun, Daniela Piani Meier, Michael Meinel: Novartis Pharma AG (salary). Peter Chin: Novartis Pharmaceuticals Corporation (salary). William Camu: Merck Serono, Teva Pharmaceuticals, Sanofi-Aventis, Bayer Schering Pharma, Biogen Idec (consulting fees).Keywords: Confirmed disability progression, Expanded Disability Status Scale, T2 lesion volume

(DX41) BRAIN VOLUME CHANGE BY QUARTILE AND DISABILITY PROGRESSION IN MULTIPLE SCLEROSIS: A 4-YEAR ANALYSIS OF THE PHASE 3 FREEDOMS TRIAL AND ITS EXTENSIONDouglas Jeffery,1 Elisabetta Verdun,2 Daniela Piani Meier,3 Shannon Ritter,3 Ernst W. Radue,4 William Camu5

1Cornerstone Health Care, High Point, NC; 2Novartis Pharma AG, Basel, Switzerland; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ; 4Medical Image Analysis Centre, University Hospital Basel, Basel, Switzerland; 5MS Clinic, Department of Neurology, Hôpital Guide Chauliac, Montpellier, France

Background: Brain volume loss (BVL) is a feature of multiple scle-rosis (MS), reflecting diffuse and focal neurologic damage. Studies have shown significant correlations between BVL and disability progression in MS. Objectives: To investigate whether the extent of BVL at month 24 associates with, and is prognostic of, disability progression over 48 months in the phase 3 FREEDOMS trial and its extension. Methods: Patients (n = 1029) were categorized post hoc from baseline (BL) to month 24 (M24) by quartile of total percentage BV change (PBVC), assessed using “Structural Image Evaluation, using Normalization, of Atrophy” (SIENA), and mean annualized PBVC from BL to M24 was determined in each quartile. Patient characteristics at BL were also determined in each quartile, as were the proportions of patients at M24 and at M48, with Expanded Disability Status Scale (EDSS) score ≥4.0 or ≥6.0 at any time and disability progression (an increase in EDSS score of ≥1.0 if BL EDSS ≤5.0, or of 0.5 if BL EDSS ≥5.5) confirmed over 3 months (CDP3) or over 6 months (CDP6). Mean change in EDSS score was also calculated from BL to either M24 or M48. Results: Quartile ranges of PBVC at M24 were Q1 (n = 256), −13.5% to −1.7%; Q2 (n = 254), −1.7% to −0.8%; Q3 (n = 257), −0.8% to −0.2%; and Q4 (n = 262), −0.2% to 3.0%. Respective mean (SD) annualized PBVC (BL-M24) was −1.5% (0.7%), −0.6% (0.1%), −0.2% (0.1%), and 0.2% (0.3%). Comparing Q1 and Q4 at BL, there were proportionately more women (74.6% vs. 68.7%); mean (SD) EDSS was greater (2.7 [1.3] vs. 2.1 [1.2]), as were T2 lesion volume (11.3 [10.2] cm3 vs. 3.3 [4.4] cm3), T1-hypointense lesion volume (3.6 [4.2] cm3 vs. 1.0 [1.9] cm3), and number of Gd+ lesions (3.1 [5.6] vs. 0.6 [1.3]). The respective proportions of patients in Q1 and Q4 with EDSS ≥4.0 were (M24) 30.3% and 11.4%, and (M48) 35.8% and 13.8%; with EDSS ≥6.0 were (M24) 14.8% and 1.1%, and (M48) 19.2% and 3.1%; with CDP3 were (M24) 22.7% and 13.4%, and (M48) 28.8% and 17.9%; and with CDP6 were (M24) 19.1% and 10.7%,

zumab 12 mg/day on 5 consecutive days at start of the extension and on 3 days 12 months later. All patients received prophylactic intravenous methylprednisolone 1 g prior to infusion on the first 3 infusion days of each treatment course. IARs were defined as any adverse event with onset during infusion or up to 24 hours after the end of an infusion. Data were pooled from patients entering the extension from both CARE-MS core studies. Results: A total of 282 patients were treated with alemtuzumab in the extension study after receiving SC IFNβ-1a in the core studies; 93.3% of patients received 2 alemtuzumab courses. The incidence of IARs declined from year 1 (83.3%) to year 2 (43.9%) of the extension study in patients who switched from SC IFNβ-1a to alemtuzumab, as was observed during the first 2 years of alemtuzumab treatment in the core studies. IARs were most frequent on the first infusion day of each treatment course. The most frequently reported IARs were rash, headache, pyrexia, nausea, urticaria, and insomnia. Serious IARs were infrequent (year 1: 0.7%; year 2: 0.4%). Conclusions: Patients who switched from SC IFNβ-1a to alemtuzumab in the CARE-MS extension study had similar incidence and severity of IARs as patients who received alem-tuzumab in the core studies. These findings support the consistent profile of IARs associated with alemtuzumab infusion across clinical trials.

Supported by: Genzyme, a Sanofi company; Bayer HealthCare PharmaceuticalsDisclosure: Carolina Ionete: Biogen Idec, Genzyme Corporation, Teva Phar-maceuticals, Acorda Therapeutics Inc, Bayer HealthCare Pharmaceuticals, EMD Serono (consulting fees, grant/research support). Jeffrey A. Cohen: EMD Serono, Genentech, Innate Immunotherapeutics, Vaccinex (consulting fees). Edward J. Fox: Bayer HealthCare, Biogen Idec, Eli Lilly, EMD Serono, Genzyme, Novartis, Ono, Opexa Therapeutics, Pfizer, Sanofi, Teva (consulting fees, grant/research support, honoraria, travel support). Hans-Peter Hartung: Bayer HealthCare, Bio-gen Idec, CSL Behring, Genzyme, Hoffmann-LaRoche, Novartis, Octapharma, Sanofi, Teva (consulting fees). Eva Havrdova: Biogen Idec, Genzyme, Merck, Novartis, Receptos (consulting fees); Biogen Idec (grant/research support). Krzysztof W. Selmaj: Biogen Idec, Roche, Merck, Synthon, Genetech, Genzyme (consulting fees). David H. Margolin: Genzyme, a Sanofi company (salary). Linda Kasten: Genzyme, a Sanofi company (consulting fees). D. Alastair S. Compston: Genzyme, Lundbeck Foundation (consulting fees).Keywords: Alemtuzumab, Disease-modifying treatments in MS

(DX40) EFFECTS OF FINGOLIMOD ON CATEGORICAL CHANGE IN T2 LESION VOLUME AND CLINICAL OUTCOMES IN PATIENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSISDouglas Jeffery,1 Elisabetta Verdun,2 Daniela Piani Meier,2 Michael Meinel,2 Peter Chin,3 William Camu4

1Cornerstone Health Care, High Point, NC; 2Novartis Pharma AG, Basel, Switzerland; 3Novartis Pharmaceutical Corporation, East Hanover, NJ; 4MS Clinic, Department of Neurology, Hôpital Guide Chauliac, Montpellier, France

Background: Clinical evidence from patients with relapsing-remitting multiple sclerosis (RRMS) suggests an association between change in T2 lesion volume (LV) and confirmed disability progression (CDP). Objectives: To investigate the association between categori-cal change in T2 LV and clinical outcomes in the FREEDOMS study and extension. Methods: This study performed post hoc analyses of T2 LV at baseline and month 24 in patients who received fingolimod 0.5 mg or placebo. Categorical subgroups were defined according to change in T2 LV from baseline to month 24: decreased (< –500 mm3); stable (≥ –500 mm3 and ≤ 500 mm3); and increased (>500 mm3). Clinical outcomes included 3- and 6-month CDP measured by mean change in Expanded Disability Status Scale (EDSS) score and Multiple Sclerosis Functional Composite (MSFC) z scores. Additional analyses assessed the relationship between LV change in the first 2 years and disability through month 48. Results: A total of 1057 of 1272 patients had T2 LV assessments at baseline and month 24. At month 24, the proportions with decreased, stable, and increased T2 LV were 15.5% (n = 164), 59.9% (n = 633), and 24.6% (n = 260), respectively. A greater proportion of patients treated with fingolimod 0.5 mg had decreased or stable LV than those receiving placebo

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(DX43) TREATMENT DISCONTINUATION AFTER INITIATION OF ORAL DISEASE-MODIFYING THERAPIES IN PATIENTS WITH MULTIPLE SCLEROSISJohn J. Ko,1 Huanxue Zhou,2 Tara A. Nazareth,3 Vivian Herrera,3 Yunfeng Li,3 Kathleen Hawker,3 Rahul Sasane3

1The University of Texas at Austin, Austin, TX; 2KMK Consulting, Inc, Florham Park, NJ; 3US Health Economics and Outcomes Research, Novartis Pharmaceuticals Corporation, East Hanover, NJ

Background: Disease-modifying therapies (DMTs) have been shown to delay progression of multiple sclerosis and reduce relapses. Little is known about treatment patterns after discontinuation of oral DMTs (ODMTs). Objectives: To describe all DMT treatment patterns after discontinuation of ODMTs (dimethyl fumarate [DMF], teriflu-nomide [TFN], or fingolimod [FTY]) in patients newly initiating these agents. Methods: A retrospective study was conducted using Truven Health MarketScan Commercial Claims and Encounters and Medi-care Supplemental and Coordination of Benefits databases. Patients newly initiating an ODMT between 4/1/13 and 6/30/13 (first ODMT claim = index date for index DMT) who were continuously enrolled for 12 months pre- (baseline) and 12 months post-index date (follow-up) were included. Patients who experienced >30 days with no supply of the index ODMT were assumed to have a gap in ther-apy (Rx gap). The last Rx gap during the follow-up was examined to gain insights into all DMT treatment patterns (switch, discontinuation, etc.). Results: The study included 1533 DMF, 146 TFN, and 196 FTY patients meeting study inclusion criteria. At the end of follow-up, 473 (30.9%) of DMF, 57 (39.0%) of TFN, and 41 (20.9%) of FTY patients had an Rx gap of >30 days. In patients with a >30 day Rx gap at the end of follow-up, more than half of those on DMF (55.8%) and TFN (52.6%) discontinued DMT treatment completely (ie, did not resume their current treatment or switch to another DMT), compared with 19.5% of those on FTY. The proportions of patients who discon-tinued DMTs completely by duration of discontinuation days were as follows: ≤180 days (8.0% DMF, 5.5% TFN, 2.6% FTY); 181–210 days (0.9% DMF, 2.7% TFN, 0.5% FTY); 211–365 days (8.3% DMF, 12.3% TFN, 1.0% FTY). Conclusions: Among patients newly initiat-ing ODMTs, those on TFN and DMF had more frequent and lengthy Rx gaps at the end of follow-up, when compared with those on FTY. Over 50% of DMF and TFN users did not restart any DMT after dis-continuing their individual oral therapy during follow-up, versus 20% of FTY users. Further exploration is needed into contributing factors, both physician- and patient-reported, such as tolerability, in order to understand differential discontinuation by ODMT and to formulate appropriate mitigation strategies.

Supported by: Novartis PharmaceuticalsDisclosure: John J. Ko, Huanxue Zhou: Nothing to disclose. Tara A. Nazareth, Vivian Herrera, Yunfeng Li, Kathleen Hawker, Rahul Sasane: Novartis Pharma-ceuticals (salary, ownership interest).Keywords: Disease-modifying treatments in MS

(DX44) MEDICATION PRESCRIBING PATTERNS ASSOCIATED WITH MULTIPLE SCLEROSIS PATIENTS TREATED WITH ORAL DISEASE-MODIFYING THERAPIESJohn J. Ko,1 Tara A. Nazareth,2 Howard Friedman,3 Prakash Navaratnam,3 Denise A. Herriott,4 Rahul Sasane2

1The University of Texas at Austin, Austin, TX; 2US Health Economics and Outcomes Research, Novartis Pharmaceuticals Corporation, East Hanover, NJ; 3DataMed Solutions LLC, Hilliard, OH; 4Outcomes Research, Indegene TTM, Kennesaw, GA

Background: There are three approved multiple sclerosis (MS) oral disease-modifying therapies (ODMTs) in-market: dimethyl fumarate (DMF), fingolimod (FTY), and teriflunomide (TFN). Per their US pack-age inserts, all three ODMTs are indicated for first-line treatment of relapsing-remitting MS (RRMS); dose escalation (DE) is recommended only for DMF in the first month of use as 120 mg twice daily (bid) for 7 days and then 240 mg bid thereafter, whereas FTY and TFN have no DE. Objectives: To provide real-world insight into ODMT prescribing patterns based on a retrospective review of the medi-

and (M48) 24.2% and 15.4%. Respective mean (SD) changes in EDSS scores in Q1 and Q4 were 0.1 (1.1) and −0.1 (0.8) for BL-M24, and 0.2 (1.2) and 0.0 (0.9) for BL-M48. Conclusions: The quartile of patients with greatest BVL at 24 months (Q1) had the greatest disease activity and severity at BL, and the most disability progression at both 24 and 48 months. This suggests that 24-month BVL is associated with long-term disability evolution.

Supported by: Novartis Pharmaceuticals CorporationDisclosure: Douglas Jeffery: Bayer, Biogen Idec, Teva Pharmaceuticals, Serono, Pfizer, Glaxo, Novartis Pharmaceuticals Corporation, Acorda Therapeutics, Genzyme, XenoPort, Alkermes, QuestCor (consulting fees). Elisabetta Verdun, Daniela Piani Meier: Novartis Pharma AG (salary). Shannon Ritter: Novartis Pharmaceuticals Corporation (salary). Ernst W. Radue: Novartis, Biogen Idec, Merck Serono, Bayer Schering (speaker fees, consulting fees); Actelion, Basilea Pharmaceutica Ltd (consulting fees). William Camu: Merck Serono, Teva Phar-ma, Sanofi-Aventis (consulting fees); Bayer Schering, Biogen Idec, Merck Serono, Teva Pharma, Sanofi-Aventis (research/grant support).Keywords: Fingolimod, Brain volume loss, Disability

(DX42) UTILIZATION AND SWITCH PATTERNS WITH DIMETHYL FUMARATE IN A PUBLICLY FUNDED DRUG PLAN: THE FIRST 8 MONTHSCharity Evans,1 Darren Nickel,2 Karlene Britton,2 Katherine Knox2

1Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada; 2Physical Medicine and Rehabilitation, University of Saskatchewan, Saskatoon, SK, Canada

Background: Dimethyl fumarate was the first oral disease-modify-ing therapy (DMT) approved for formulary coverage under the pub-licly funded drug plan in Saskatchewan, Canada, for first-line treat-ment of relapsing-remitting multiple sclerosis (MS). Tracking requests for drug coverage in a publicly funded system provides unique information related to utilization patterns and insight into rationale for treatment decisions concerning drug initiations and switches. Objec-tives: Describe the utilization patterns (initiations and switches) of dimethyl fumarate, and explore the reasons for switches provided by the prescribing physician for people covered by the publicly funded drug plan in Saskatchewan. Methods: Utilization data came from the Saskatchewan MS Drugs Research Program starting from the formulary approval date for dimethyl fumarate (1 May 2014). All publicly funded DMT requests are processed through the Saskatch-ewan MS Drug Program, ensuring a high rate of capture. Preliminary descriptive statistics are reported. Results: As of 6 January 2015, 857 people were receiving coverage for an approved DMT through the Saskatchewan MS Drugs Program, including 239 (27.9%) for dimethyl fumarate. From May to December 2014, 285 applica-tions were approved for dimethyl fumarate: 68 new starts and 217 switching from another DMT. Among the 217 applications switching to dimethyl fumarate, 45.6% and 76.0% switched within the first 3 and 6 months, respectively, from the time the drug received formulary approval. Preliminary analysis suggests the main reasons for switch-ing to dimethyl fumarate were injection fatigue, relapses/progres-sion, injection-site reactions, and intolerable side effects. Switching from dimethyl fumarate to other DMTs was first observed 6 months after formulary approval (n = 21). Further analyses and updates of switches will be reported in the final poster. Conclusions: Uti-lization of dimethyl fumarate in a publicly funded system began immediately after formulary approval. Switches in the first 6 months were from other DMTs to dimethyl fumarate; however, switching from dimethyl fumarate to other DMTs has subsequently increased. Further examination of reasons for switching, and other utilization patterns including adherence, may help identify previously unrecognized adverse effects, as well as guide MS management and future health policy.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Disease-modifying treatments in MS

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values > 0.05). A greater percentage of SC IFNβ-1a patients report-ed high adherence compared with SC IFNβ-1b patients (58.8% vs. 33.3%, P = .0025). After adjusting for covariates, SC IFNβ-1a patients had greater odds of high adherence (odds ratio [OR] 2.92; P = .0101). Male sex (OR 4.37; P = .0297), time since last relapse (years; OR 1.04; P = .0483), frequent exercise (OR 1.06; P = .0094), and Patient-Determined Disease Steps score (OR 1.34; P = .0110) were predictive of high adherence. Conclusions: In this exploratory analysis, treatment with SC IFNβ-1a tiw was strongly associated with high adherence relative to SC IFNβ-1b eod.

Supported by: EMD Serono, Inc, a subsidiary of Merck KGaA; Pfizer IncDisclosure: Chris M. Kozma: EMD Serono, Inc (grant/research support). Amy L. Phillips, Julie C. Locklear: EMD Serono, Inc, a subsidiary of Merck KGaA (salary).Keywords: Disease-modifying treatments in MS, DMD adherence

(DX46) BEST PRACTICE RECOMMENDATIONS OF ADVANCED PRACTICE CLINICIANS FOR THE CARE OF THE CHALLENGING MULTIPLE SCLEROSIS PATIENTJohn Kramer,1 Christina Caon,2 Gregory Bjorklund,3 Mary Filipi,4 Jennifer Ravenscroft,5 Amy Perrin Ross,6 Colleen E. Miller7

1Center for Neurological Disorders, Wheaton Franciscan Healthcare, Milwaukee, WI; 2Wayne State University School of Medicine, Detroit, MI; 3Sanford Health, Moorhead, MN; 4MS Center of Nebraska, Lincoln, NE; 5Kansas City MS Center, Olathe, KS; 6Loyola University Medical Center, Maywood, IL; 7Genzyme, a Sanofi company, Cambridge, MA

Background: The heterogeneity of multiple sclerosis (MS) and treatment response make individualized therapy a logical approach, but health-care providers often face the challenge of balancing dis-ease- and patient-related considerations to determine optimal disease management. The role of advanced practice clinicians (APCs) in MS patient care is becoming increasingly complex with the evolving therapeutic landscape and heightened patient expectations. Objec-tives: To examine best practices for the management of the chal-lenging MS patient and identify knowledge gaps and educational needs of health-care providers specializing in MS care based on recommendations from an expert panel of APCs. Methods: The expert panel of 25 APCs, which included nurse practitioners and physician assistants from diverse clinical practice types in the United States and Canada, specializing in the treatment and management of MS patients, discussed and delineated the characteristic profile of the challenging MS patient. Approaches to treatment, use of disease-modifying therapies (DMTs), and patient management, including indi-vidualized patient therapy, were considered. Results: Three areas were identified as potential barriers to optimizing treatment outcomes in MS: disease activity, patient characteristics, and practical consider-ations. Disease-related considerations included magnetic resonance imaging (MRI) activity while on DMT, presence of brainstem or spinal cord lesions, progressive disease, and abnormal laboratory results. Patient-specific characteristics were JC virus–positive status, exposure to previous immunosuppressants, and treatment-naive status. Practi-cal considerations such as poor treatment adherence due to either administration mode or adverse events, poor socioeconomic status, and limited health-care access could also negatively affect outcomes. Some best practices toward addressing these risk factors for poor out-comes were highlighted, including effective communication between MS specialists and primary-care providers, routine MRI assessment to monitor disease progression, and early treatment initiation to enable early switching to alternative treatment if needed. Conclusions: A gap in the organized presentation of basic scientific information and practical aspects of MS care was identified. Efforts to address this gap will engender greater awareness of the considerations involved in the management of challenging MS patients.

Supported by: EMD Serono, Inc, a subsidiary of Merck KGaA; Pfizer Inc; Gen-zyme, a Sanofi companyDisclosure: John Kramer: Biogen, Genzyme, Teva, Novartis (consulting fees); Biogen, Novartis, Genzyme (grant/research support). Christina Caon: Genzyme, MS Atrium (consulting fees). Gregory Bjorklund, Mary Filipi: Genzyme (consult-ing fees). Jennifer Ravenscroft: Genzyme, Biogen Idec, Acorda, Questcor (consult-

cal records (MRs) of US patients with MS. Methods: In our study, 259 distinct medical records (MRs) of MS-diagnosed patients using ODMTs were abstracted from 19 United States–based neurology clin-ics between 12/31/10 and 06/30/14 (DMF: 133; FTY: 67; TFN: 59). Eligible patients had three or more visits—one visit related to ODMT initiation (defined as index visit), two or more MS-related visits (one within the 12 months prior to and one within the 12 months fol-lowing ODMT initiation)—and documented age and gender. ODMT prescribing patterns (ie, medication switching, discontinuation, restarts, and add-ons) were tracked in the pre- and post-index win-dows; DE was evaluated at 1–3, 4–6, 7–9, and 10–12 month (mo) intervals, as well as cumulatively, in patients with complete follow-up. Results: MS-related medication switching, reduction, restarting, and add-ons were observed infrequently (each outcome identified in ≤3% within 9 months; ≤4% within 12 months) and similarly across ODMT cohorts in our study. Assessment of DE with DMF over 9 months (167 of 259 MRs) and 12 months (132 of 259 MRs) was as follows: at 9 months (9.4% at 1–3 mo, 15.3% at 4–6 mo, 21.2% at 7–9 mo) and at 12 months (9.2% at 1–3 mo, 13.9% at 4–6 mo, 23.1% at 7–9 mo, 0% at 10–12 mo). Over 1–9 months, 45.9% of patients on DMF had DE; a similar proportion was seen over 1–12 months (46.2%). Conclusions: MRs provide valuable insight into important aspects of provider and patient behavior, but are subject to documentation practices. There were no observed differences in the medication prescribing patterns for ODMTs, with the exception of DE. With regard to DE, delays were observed in titration to the therapeutic dose of DMF at every interval, as well as up to 9 months after initiation. Adverse implications of a delay in DE on key disease outcomes such as prevention of relapses and slowing of disease pro-gression, as well as associated cost, should be explored. Additional insights to support tailored prescribing of ODMT agents are needed.

Supported by: Novartis Pharmaceuticals CorporationDisclosure: John J. Ko: Nothing to disclose. Tara A. Nazareth, Rahul Sasane: Novartis Pharmaceuticals (salary, ownership interest). Howard Friedman: Merck & Company, Novartis, BMS (grant/research support). Prakash Navaratnam: Merck & Company, Novartis, BMS, Gilead (grant/research support). Denise A. Herriott: DataMed Solutions (grant/research support).Keywords: Disease-modifying treatments in MS, Treatment patterns

(DX45) PREDICTORS OF ADHERENCE USING PANEL SURVEY DATA FROM MULTIPLE SCLEROSIS PATIENTS CURRENTLY TREATED WITH HIGH-DOSE, HIGH-FREQUENCY INTERFERONSChris M. Kozma,1 Amy L. Phillips,2 Julie C. Locklear2

1Independent Research Consultant, Saint Helena Island, SC; 2EMD Serono, Inc, Rockland, MA

Background: Treatment adherence is important for optimizing patient care in multiple sclerosis (MS). Objectives: To evaluate the relationship between treatment with high-dose, high-frequency inter-ferons and adherence among MS patients. Methods: A random sample of relapsing-remitting MS patients (age ≥18 years, clinical trial–naïve) from the US National Health and Wellness Survey or Lightspeed Research panel completed an Internet survey in Novem-ber/December 2012. Adherence was evaluated among those indicating current treatment (≥4 months) with subcutaneous inter-feron beta-1a (SC IFNβ-1a) three times weekly (tiw) or subcutaneous interferon beta-1b (SC IFNβ-1b) every other day (eod). Adherence was measured using the four-item Morisky Medication Adherence Scale (forget to take medication, careless at times about taking, stop if better, stop if worse; high adherence = all negative responses). Baseline characteristics were compared using chi-square and t tests. Logistic regression evaluated the relationship between SC IFNβ-1a or SC IFNβ-1b treatment and the odds of having high adherence. Covariates included age, sex, exercise, and therapy-related variables (months on therapy, satisfaction, perception of effectiveness, cost). Results: Of 969 surveyed, 80 SC IFNβ-1a and 63 SC IFNβ-1b patients met inclusion criteria (mean [SD] age: 49.0 [10.4] years, 88.8% female vs. 51.3 [8.7] years, 87.3% female, respectively; P

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(MRI) benefits versus placebo in patients with relapsing-remitting multiple sclerosis (RRMS). In the 2-year extension, outcomes were consistently better for patients who continued on Rx44 versus patients who switched from placebo to IFNβ-1a SC after 2 years (delayed treatment; DTx). Objectives: To examine the predictive value of early MRI results for future clinical outcomes of patients receiving DTx or continuous IFNβ-1a SC tiw treatment. Methods: In PRISMS-2, all patients had T2-weighted scans twice yearly; a frequent-MRI cohort (n = 205) had monthly T2 and T1 gadolinium-enhancing (Gd+) scans before and during the first 9 months. Post hoc analysis examined cumulative mean numbers of Gd+ and active (new/enlarging) T2 lesions/patient/scan; analysis of the entire cohort by presence or absence of T2 lesions at 6 months assessed the predic-tive value of early MRI response for EDSS worsening (increase ≥1 point if baseline ≤5.5, or increase of 0.5 point if baseline ≥6), EDSS progression (worsening confirmed 3 months later), and relapses over 2 or 4 years. Results: IFNβ-1a SC tiw was associated with significantly (P < .05) fewer Gd+ (from 2 months) and active T2 (from 3 months) lesions/patient/scan versus placebo in analysis of frequent-MRI cohort data. In the overall PRISMS cohort, 147/187 (78.6%) patients in the DTx group had ≥1 active T2 lesion at 6 months versus 100/189 (52.9%) and 87/184 (47.3%) patients in the Rx22 and Rx44 groups. In the DTx group, 42.9% with 6-month T2 lesions versus 25.6% without had confirmed EDSS progression, 74.1% versus 53.8% had any EDSS worsening, and 89.1% versus 66.7% had relapses over 2 years; presence of 6-month T2 lesions had positive predictive values of 74.1% and 89.1% for EDSS wors-ening and relapse over 2 years. In the Rx22 group, 37.0% versus 25.9% of patients with or without 6-month T2 lesions had confirmed EDSS progression, 59.0% versus 51.8% had any EDSS worsening, and 79.0% versus 68.2% had relapses over 2 years. In the Rx44 group, 23.0% versus 31.6% of patients with or without 6-month T2 lesions had confirmed EDSS progression, 50.6% versus 53.7% had any EDSS worsening, and 65.5% versus 70.5% had relapses over 2 years. 4-year results were similar. Conclusions: Presence of T2 lesions after 6 months of placebo administration was predictive of poorer long-term clinical outcomes; T2 lesions at 6 months in patients receiving IFNβ-1a 44 µg SC tiw were not associated with poorer clinical outcomes.

Supported by: EMD Serono, Inc, a subsidiary of Merck KGaA; Pfizer IncDisclosure: Mark Cascione: Acorda, Bayer HealthCare, Biogen Idec, EMD Serono, Genentech, Genzyme/Sanofi, Novartis, Pfizer, Roche, Teva (grant/research support, consulting fees, speakers’ bureau). David Li: Genzyme, Hoff-mann-LaRoche, Merck Serono, Nuron, Perceptives, Sanofi-Aventis (grant/research support); Genzyme (consulting fees); Novartis, Nuron, Opexa, Roche (advisory boards). Fernando Dangond, Juanzhi Fang: EMD Serono, Inc, a subsidiary of Merck KGaA (salary). Anthony Traboulsee: Biogen, Chugai, Genzyme, MedIm-mune, Novartis, Roche, Serono, Teva Innovation (consulting fees); Genzyme, Roche (grant/research support). Guojun Zhao, Yan Cheng: Nothing to disclose. Aaron Miller: Acorda Therapeutics Inc, Biogen Idec, CVS Caremark, EMD Sero-no Inc, Genzyme/Sanofi-Aventis, GlaxoSmithKline, Novartis, Nuron Biotech Inc, Ono, Questcor (advisory board, consulting fees); Acorda, Biogen Idec, Genentech, Genzyme/Sanofi-Aventis, Questcor, Roche (grant/research support).Keywords: Disease-modifying treatments in MS, Imaging and MS, Interferon beta

(DX49) DIMETHYL FUMARATE EFFECTS ON LYMPHOCYTE PHENOTYPEErin E. Longbrake, Michael J. Ramsbottom, Laura Piccio, Anne H. Cross

Neurology, Washington University, St. Louis, MO

Background: Lymphopenia developed in ~5% of patients treated with dimethyl fumarate (DMF) in phase 3 clinical trials; subsequent data suggest that lymphopenia may be even more common in clini-cal practice. A case of progressive multifocal leukoencephalopathy (PML) was recently identified in a lymphopenic DMF-treated patient. Several additional cases of PML had previously been reported in lym-phopenic patients treated with older fumarate compounds. Lympho-penia was the clearest risk factor for PML in all these patients. Surpris-

ing fees). Amy Perrin Ross: Biogen, EMD Serono, Pfizer, Bayer HealthCare, Teva, Genzyme, Novartis, Questcor, Acorda (speakers’ bureau); EMD Serono, Pfizer, Bayer HealthCare, Teva, Genzyme, Novartis, Questcor, Acorda (consult-ing fees). Colleen E. Miller: Genzyme (salary).Keywords: Comprehensive care and MS, Disease-modifying treatments in MS, Nursing management in MS

(DX47) THE TOPOGRAPHICAL MODEL OF MULTIPLE SCLEROSIS: A NEW VISUALIZATION OF DISEASE COURSEStephen Krieger

Neurology, Icahn School of Medicine at Mount Sinai, New York, NY

Background: Both inflammatory (relapsing) and neurodegen-erative (progressive) processes contribute to multiple sclerosis (MS) disease course, but neither the relationship between them nor the spectrum of clinical heterogeneity is fully characterized in current clinical course categories. We have previously shown both diagnos-tic and prognostic uncertainty inherent in applying these categories to individual patients. A conceptually lucid, biologically informed model could build on these categories to encompass the admixture of factors underlying MS disease course. Objectives: To develop a new unified MS clinical course model. Methods: The model design encapsulates five factors: topographical distribution of lesions and relapses they cause; relapse frequency, severity, and recovery; and progression rate. The model visually depicts the interplay of factors utilizing 3D animated renderings. The CNS is represented as a pool, with a shallow end and a deep end. Spinal cord and optic nerves occupy the shallow end, the posterior fossa comprises the middle, and the cerebral hemispheres constitute the deep end, each with increasing amounts of functional reserve. MS lesions rise up as topographical peaks from the pool floor. The water’s surface depicts the clinical threshold: lesions below the surface are clinically silent; those that cross it cause clinical relapses. Progression is depicted as the slowly dropping water level, representing depletion of functional capacity. Thus, like symptom recrudescence in Uhthoff’s phenomenon and pseudoexacerbations, progression clinically recapitulates the form of prior relapses/lesions, incrementally revealing above the sur-face the underlying lesion topography. Results: A dynamic, 3D-ren-dered visualization of the topographical model will be shown. Clini-cal and magnetic resonance imaging (MRI) correlates of the depicted factors will be elucidated. Conclusions: This model depicts MS disease course in a clinically nuanced way that complements the clinical course categories. It illuminates several well-described but poorly reconciled phenomena, including the clinical/MRI paradox, impact of MRI lesion burden on late (but not early) disease outcomes, and prognostic importance of brainstem and cord lesions. The model is congruent with emerging data on brain atrophy, and the protective effect of large baseline brain volume. The topographical model can be used as an educational tool for patients and professionals, and predictive implications can be empirically tested by application to clinical trial datasets.

Supported by: NoneDisclosure: Acorda, Bayer, Biogen Idec, Genentech, Genzyme, Questcor, Teva (consulting fees)Keywords: Education about MS, Imaging and MS, Natural history of MS

(DX48) PREDICTIVE VALUE OF EARLY MRI MEASURES IN PATIENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSIS RECEIVING INTERFERON BETA-1A SC TIW OR PLACEBO: POST HOC ANALYSES OF PRISMS DATAMark Cascione,1 David Li,2 Fernando Dangond,3 Juanzhi Fang,3 Anthony Traboulsee,2 Guojun Zhao,2 Yan Cheng,2 Aaron Miller4

1Tampa Neurology Associates, South Tampa Multiple Sclerosis Center, South Tampa, FL; 2University of British Columbia, Vancouver, BC, Canada; 3EMD Serono, Inc, Rockland, MA; 4Mount Sinai Hospital, New York, NY

Background: In the PRISMS-2 study, interferon beta-1a (IFNβ-1a) subcutaneous (SC) three times weekly (tiw), 22 and 44 µg (Rx22 and Rx44), demonstrated clinical and magnetic resonance imaging

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AEs considered related to treatment occurred in two subjects: one subject experienced headache on teriflunomide and on colesevelam hydrochloride; one subject experienced flatulence, nausea, and abdominal pain on cholestyramine. All subjects recovered from AEs. Conclusions: Administration of colesevelam hydrochloride for 11 days was sufficient to reduce plasma teriflunomide concentrations by >96%. Where an AEP to eliminate teriflunomide is indicated, in some patients colesevelam hydrochloride may offer an alternative method of elimination of teriflunomide with improved gastrointestinal tolerability.

Supported by: Genzyme, a Sanofi companyDisclosure: Catherine Lunven, Zuyu Guo, Sandrine Turpault, Astrid Delfolie: Sanofi (salary). Nicolas Fauchoux: Biotrial (salary). Timothy Turner, Francesca Baldinetti: Genzyme, a Sanofi company (salary).Keywords: Disease-modifying treatments in MS, Management of activities of daily living in MS, teriflunomide accelerated elimination procedure

(DX51) TRANSVERSE MYELITIS PRESENTING IN A PATIENT WITH HUGHES-STOVIN SYNDROMEJason H. Margolesky, Leticia Tornes

Neurology, University of Miami, Miami, FL

Background: Hughes-Stovin syndrome (HSS) is a lymphocytic vasculitis defined by the constellation of venous thrombosis and pulmonary artery aneurysms. HSS is thought of as a forme fruste of Behcet’s syndrome (BS), with similar histology, but without associ-ated manifestations that characterize BS. HSS does not present with oral and genital ulcers, inflammatory eye disease, skin pathergy, or the neurologic manifestations that can arise with BS. We report the first case of transverse myelitis (TM) in a patient with HSS. Case Report: A 38-year-old woman developed a deep vein thrombosis in 2009 and 3 years later presented with recurrent hemoptysis. Chest CT-angiogram showed multiple pulmonary artery aneurysms. Lung biopsy revealed a lymphocytic vasculitis, leading to the diagnosis of HSS. Treatment included intravenous (IV) methylprednisolone fol-lowed by oral immunosuppressant medications. She remained stable until June 2014, when she developed bilateral leg paresthesias and trouble with her gait. She then developed bilateral hand and leg weakness, diffuse hyperreflexia, and a thoracic sensory level to pinprick on the right with reduced vibration sense in the left leg. She admitted to medication nonadherence. Magnetic resonance imag-ing (MRI) of her thoracic spine showed nonenhancing hyperintense lesions on T2 from level T1 to T8. Her symptoms improved with a 5-day course of IV methylprednisolone, and then she was prescribed azathioprine. Repeat MRI showed resolution of the thoracic lesions. At follow-up she had persistent leg paresthesias and reduced vibra-tory sense, with full strength. Discussion: HSS is a rare disease with no formal diagnostic criteria, characterized by venous thrombosis and multiple pulmonary artery aneurysms. With similar histopathol-ogy, it can be thought of as a forme fruste of BS. BS is an autoinflam-matory disorder with diagnostic findings in addition to aneurysm formation and thromboses. BS can have neurologic manifestations including TM. With nonadherence to immunosuppressants our patient developed a steroid-responsive TM. In HSS, the development of any neurologic manifestation is atypical. To our knowledge this association has not been previously reported. This case supports the concept of HSS and BS as a spectrum of a unified disorder. A similar pathophysiology seems to underlie the two syndromes, and BS may represent a more full phenotype of this pathophysiology with multisystem involvement. Conclusion: HSS may be a forme fruste of BS. The truncated classic form of HSS can blossom into a disease that involves the central nervous system. Acute management with IV corticosteroids was effective in our case. Adherence to immunosup-pressant therapy may prevent such progression. Future case reports of patients with HSS developing unexpected complications will help further define the full spectrum of the disease.

Disclosure: Nothing to discloseKeywords: Behcet’s syndrome

ingly, little is known about DMF-induced lymphopenia, and with the growing concern about opportunistic infections in patients chronically treated with this medication, it will be important to characterize the cellular populations most affected by this drug. Objectives: To phenotypically characterize circulating lymphocytes in DMF-treated patients. Methods: Cross-sectional analysis of patient samples. Patients who had been stably treated with DMF for >6 months were classified as lymphopenic based on absolute lymphocyte counts <800 (grade 2 lymphopenia or worse). Samples were collected from lymphopenic and nonlymphopenic DMF-treated patients, untreated multiple sclerosis (MS) patients, and healthy controls and then phe-notypically characterized using flow cytometry. Results: Multiple lymphocyte populations were reduced in lymphopenic patients. These included CD4+ T cells and T-regulatory cells. However, the strongest effect was on CD8+ lymphocytes, which were almost entirely lost. In nonlymphopenic DMF-treated patients, CD4+ cells were not notice-ably affected, although CD8+ lymphocytes remained decreased com-pared to controls. Conclusions: DMF can affect many lymphocyte populations, but the drug’s strongest effect appears to be on CD8+ lymphocytes. As CD8+ cells are important for cell-mediated immu-nity and viral clearance, it will be important to determine whether the function of CD8+ lymphocytes is also impaired in DMF-treated patients.

Supported by: National Center for Advancing Translational Sciences, National Institutes of Health (grant UL1 TR000448)Disclosure: Erin E. Longbrake: Genzyme (consulting fees). Michael J. Ramsbot-tom, Laura Piccio: Nothing to disclose. Anne H. Cross: Biogen Idec, Genentech, Novartis, Sanofi-Aventis/Genzyme, Teva Neurosciences (consulting fees); EMD-Serono (clinical trial); National Multiple Sclerosis Society, National Institutes of Health (advisory board); Roche (clinical trial, consulting fees).Keywords: Disease-modifying treatments in MS, Immunology and MS

(DX50) INVESTIGATION OF THE EFFECTIVENESS AND TOLERABILITY OF COLESEVELAM HYDROCHLORIDE FOR ACCELERATED ELIMINATION OF TERIFLUNOMIDE IN HEALTHY SUBJECTSCatherine Lunven,1 Zuyu Guo,2 Sandrine Turpault,2 Astrid Delfolie,1 Nicolas Fauchoux,3 Timothy Turner,4 Francesca Baldinetti4

1Sanofi R&D, Chilly-Mazarin, France; 2Sanofi US, Bridgewater, NJ; 3Biotrial, Rennes, France; 4Genzyme, a Sanofi company, Cambridge, MA

Background: Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing-remitting multiple sclerosis (MS). Teriflunomide has a half-life of 19 days, and it takes an aver-age of 8 months for plasma concentrations to reach 0.02 µg/mL, the lower limit of detection. In cases of emerging toxicity, overdose, or pregnancy, elimination of teriflunomide can be accelerated by oral administration of cholestyramine. Colesevelam hydrochloride may offer an alternative method of elimination if well tolerated by patients. Objectives: To investigate the efficacy of oral colesevelam hydrochloride for the accelerated elimination of teriflunomide and capture information on tolerability and safety of colesevelam hydro-chloride. Methods: This was an open-label single-center study. Healthy men and women aged 18–45 years received teriflunomide 70 mg once daily for 5 days, immediately followed by an 11-day accelerated elimination procedure (AEP) of colesevelam hydrochlo-ride (4.375-g total daily dose, [4 + 3] 625-mg tablets). Blood was sampled throughout the study for determination of plasma terifluno-mide concentration via validated liquid chromatography with tandem mass spectrometry methodology. If plasma teriflunomide concentra-tion was >0.02 µg/mL at day 17 (end of AEP), subjects received precautionary cholestyramine 4 g three times daily (12-g total daily dose) until teriflunomide concentration was ≤0.02 µg/mL. Safety and tolerability were evaluated. Results: A total of 18 subjects were treated. Mean (SD) plasma teriflunomide concentration was 36.3 (6.42) µg/mL at day 6 (start of AEP) and 1.33 (0.833) µg/mL at day 17 (end of 11-day AEP), a mean 96.1% decrease (coef-ficient of variation 3.51%). After the AEP, all subjects received cho-lestyramine for 11 days to attain teriflunomide ≤0.02 µg/mL. There were no serious adverse events (AEs). Moderate treatment-emergent

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was to determine whether T25FW performance can reflect disease state, and ultimately predict if a patient will develop SPMS. Meth-ods: The Multiple Sclerosis Center at the University of Massachusetts Medical School maintains a Microsoft Access database containing over 26,000 patient encounters from over 4000 patients. We used built-in SQL coding to conduct a retrospective statistical analysis of the patient visit information database. Results: We determined that patients who ultimately progressed to SPMS had significantly slower performance on the T25FW during the RRMS phase than patients who did not progress. Moreover, we discerned that RRMS patients who had T25FW scores of longer than 8 seconds at any point during their disease were more likely to progress to SPMS. Conclusions: These results suggest that the T25FW can reflect differences in RRMS patients at risk for disease progress, and might predict a patient’s general risk for disease progression.

Disclosure: Nothing to discloseKeywords: Comprehensive care and MS, Epidemiology of MS, Natural history of MS

(DX54) AN ASSESSMENT OF ADHERENCE AMONG MULTIPLE SCLEROSIS PATIENTS NEWLY INITIATING TREATMENT WITH A SELF-INJECTABLE VERSUS ORAL DISEASE-MODIFYING DRUGMichael Munsell,1 Julie C. Locklear,2 Amy L. Phillips,2 Molly Frean,1 Joseph Menzin1

1Boston Health Economics, Inc, Waltham, MA; 2EMD Serono, Inc, Rockland, MA

Background: As the multiple sclerosis (MS) disease-modifying drug (DMD) class expands with oral entrants, it is important to understand how oral therapy may affect adherence. Objectives: To evaluate adherence among MS patients newly initiating a self-injectable versus oral DMD. Methods: MS patients (age 18–63 years; ≥1 medical claim with MS diagnosis: ICD-9-CM:340.xx) with ≥1 DMD claim (first claim = index date), with continuous eligibility 12 months pre- and post-index, and with no DMD use during the pre-index period, were identified from a random sample of 5 million lives in the IMS LifeLink Plus database from 7/1/2010 to 6/30/2013. Patients were stratified by index DMD type: self-injectable versus oral. Fisher and Wilcoxon tests were used in unadjusted statistical comparisons. Logis-tic regression was used to evaluate the likelihood of nonadherence (12-month post-index categorical medication possession ratio <0.8 vs. ≥0.8) to index DMD group. Covariates included age, sex, and baseline comorbidities. Results: The analysis included 5238 self-injectable and 444 oral DMD patients (mean age: 43.0 vs. 44.0, respectively; P = .0418). In unadjusted analyses, the percentage of patients who were nonadherent in the self-injectable (45.2%) and oral (41.8%) DMD groups did not differ statistically (P = .1791). After controlling for covariates, index DMD type was not a significant predictor of nonadherence (P = .1858). Male sex and older age groups (vs. 18–34) were associated with significantly lower likeli-hood of nonadherence (odds ratio [OR]: 0.811 and ORs: 0.697–0.813, respectively; P < .05). Depression was associated with higher likelihood of nonadherence (OR: 1.732, P < .0001). Conclusions: In this analysis, there was no difference in nonadherence attributable to self-injectable versus oral DMDs. Male sex and older age were associated with a lower risk of nonadherence, and depression was associated with a higher risk of nonadherence.

Supported by: EMD Serono, Inc, a subsidiary of Merck KGaA; Pfizer IncDisclosure: Michael Munsell, Molly Frean, Joseph Menzin: EMD Serono (fund-ing); Boston Health Economics, Inc (salary). Julie C. Locklear, Amy L. Phillips: EMD Serono, Inc, a subsidiary of Merck KGaA (salary).Keywords: Disease-modifying treatments in MS, DMD adherence

(DX55) OLIGOCLONAL BANDING PATTERNS IN PATIENTS WITH MULTIPLE SCLEROSISKayleigh Da, Jill R. Nelson, George Medvedev, Galina Vorobeychik


(DX52) EFFECT OF ORAL FINGOLIMOD TREATMENT ON ANNUALIZED RELAPSE RATES IN PATIENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSIS USING BAYESIAN METHODOLOGYGuosheng Yin,1 Xiangyi Meng,2 Zahur Islam,2 Ralph Kern2

1Department of Statistics and Actuarial Science, The University of Hong Kong, Pokfulam Road, Hong Kong; 2Novartis Pharmaceuticals Corporation, East Hanover, NJ

Background: FREEDOMS and FREEDOMS II, both 24-month, randomized, double-blind, placebo-controlled phase 3 studies, have demonstrated the superior efficacy of fingolimod over pla-cebo in patients with relapsing-remitting multiple sclerosis (RRMS), as assessed by relapse rates and magnetic resonance imaging outcomes. Primary analyses in each study estimated annualized relapse rates (ARRs) by means of a negative binomial model (NBM) after adjusting for covariates. The quality of current analysis of FREE-DOMS II data may be enhanced by use of historical information from the prior study (FREEDOMS). Objectives: To estimate ARRs in patients with RRMS treated with fingolimod 0.5 mg once daily in the FREEDOMS II study using a Bayesian power prior approach. Methods: Bayesian power prior methodology with historical data from FREEDOMS as the informative prior was used to estimate ARRs for fingolimod 0.5 mg versus placebo in FREEDOMS II. Results: Analysis of FREEDOMS II data using NBM estimated a 47.8% reduc-tion in ARR in patients treated with fingolimod relative to placebo (ARR: 0.21; 95% confidence interval [CI]: 0.17-0.25 vs. 0.39; 95% CI: 0.34-0.46, respectively). The Bayesian analysis with noninforma-tive prior (zero weight given to prior study data) estimated a 48.0% reduction in ARR in patients treated with fingolimod relative to pla-cebo (ARR: 0.21; 95% Bayesian credible interval [BCI]: 0.15-0.28 vs. ARR: 0.39; 95% BCI: 0.33-0.47, respectively). Applying equal weight to the likelihoods of prior and current study data resulted in an estimated reduction in ARR of 52.4% (ARR: 0.21; 95% BCI: 0.18-0.25 vs. ARR: 0.44; 95% BCI: 0.40-0.48, respectively). Power priors with weights from 0.1 to 0.9 in increments of 0.1 have been explored, and the deviance information criterion will be applied to determine the best fitting of power prior. Conclusions: Bayesian power prior methodology applied to FREEDOMS II data provided estimates of ARRs similar to those obtained with NBM, which were consistent with results previously reported in phase 3 fingolimod studies.

Supported by: Novartis Pharmaceuticals CorporationDisclosure: Guosheng Yin: Nothing to disclose. Xiangyi Meng, Zahur Islam, Ralph Kern: Novartis Pharmaceuticals Corporation (salary).Keywords: Annualized relapse rate, Bayesian analysis, Fingolimod

(DX53) ANALYSIS OF THE 25-FOOT TIMED WALK TEST AS A PREDICTIVE FACTOR IN MULTIPLE SCLEROSIS DISEASE PROGRESSIONJyotsna Mullur

University of Massachusetts Medical School, Worcester, MA

Background: Patients with multiple sclerosis (MS) often are diag-nosed with relapsing-remitting MS (RRMS), characterized by stable disease punctuated with intermittent flares of symptoms. Eventu-ally, some patients progress to secondary progressive MS (SPMS), in which the disease steadily worsens over time. Currently, a patient’s disease status is determined on a holistic basis by considering the neurologic examination, radiologic findings, and tests of physical function, including the Timed 25-Foot Walk (T25FW). Determination of a patient’s disease status heavily informs intervention and treat-ment. Nonetheless, despite such extensive clinical assessment, there remains no definitive objective measure to define a patient’s disease status or predict progression risk over time. Identification of specific prognostic factors in MS disease progression would be highly appli-cable to more precise anticipation of disease outcomes, and accord-ingly, improving therapeutic approaches. Objectives: Our goal

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equal comparison of options across all agents, decisions had to be made in terms of the chosen clinical studies (such as time frame, quality of study, and clinical outcomes) and content of options. To comply with the one-page format and sixth-grade reading level that OGs use, editing decisions were made in terms of the presentation of data. The evidence document accompanying each OG transparently describes the criteria used to generate the information about each option. Results: Development of the OGs was initiated in Summer 2012, with anticipated publication by Spring 2014 on the Option Grid Collaborative website, where they will be freely available in the public domain at http://www.optiongrid.org/optiongrids.php. Challenges during the development and editing process regarding selection of studies, content, and presentation of data were met and resolved. Specific challenges encountered included tradeoffs between specificity and usability, brevity and exhaustiveness, and detail and compliance with the bounded rationality approach. Peer review and patient focus group feedback suggest that the OGs will be practical, feasible to use, and helpful to patients and caregivers. Conclu-sions: Evidence-based, peer-reviewed, and patient-advised OGs for DMTs in relapsing-remitting MS (RRMS) can be incorporated in the clinical setting in a shared decision-making approach, and have the potential to increase patient empowerment and decision quality in DMT treatment decisions. Clinical testing will follow to explore the effects of OGs on DMT decision quality and treatment adherence.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Disease-modifying treatments in MS, Shared decision-making

(DX57) PEGINTERFERON BETA-1A AND MANAGEMENT STRATEGIES FOR FLU-LIKE SYMPTOMS AND INJECTION-SITE REACTIONS: OBTAINING RECOMMENDATIONS USING THE DELPHI TECHNIQUEScott D. Newsome,1 Diego Centonze,2 DeRen Huang,3 June Halper,4 Christopher Robertson,5 Xiaojun You,5 Guido Sabatella,5 Vladimir Evilevitch,5 Leslie Leahy5

1Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD; 2Multiple Sclerosis Clinical Center, Policlinico Universitario Tor Vergata, Rome, Italy; 3Neurology and Neuroscience Associates, Akron, OH; 4Consortium of Multiple Sclerosis Centers, Hackensack, NJ; 5Biogen Idec Inc, Cambridge, MA

Background: Side effects, including flu-like symptoms (FLS) and injection-site reactions (ISR), have been reported with interferon treat-ment. These side effects can affect patient adherence and thus treat-ment outcome in patients with multiple sclerosis (MS). Objectives: To obtain consensus on the characteristics and management of FLS and ISR associated with peginterferon beta-1a treatment using Delphi methodology. Methods: ADVANCE was a double-blind, random-ized, placebo-controlled study of subcutaneous peginterferon beta-1a 125 µg given every 2 or 4 weeks in MS patients. Investigators of the ADVANCE study with a predefined number of enrolled patients (≥2 in United States and ≥10 elsewhere) were offered the opportunity to participate in the Delphi process. An independent steering committee (n = 4) oversaw the development of two questionnaires designed to better understand frequency, duration, and impact of FLS and ISR and to generate consensus recommendations for management of these side effects. An average rating (AR) of ≥2.7 based on Likert scale (1 = strongly disagree, 2 = disagree, 3 = agree, 4 = strongly agree) was defined as the response level for consensus. Results: 29 investigators who had completed questionnaire 1 also completed questionnaire 2. Responders agreed that, for most patients, FLS typically last ≤24 hours (AR: 3.17) and have only mild to moderate impact on activities of daily living (AR: 3.34). Responders recom-mended that patients who begin treatment should be advised to take acetaminophen/NSAID (AR: 3.31) on a scheduled basis and change the timing of peginterferon beta-1a injection (AR: 3.28) to manage FLS. When asked about ISR associated with peginterferon beta-1a administration, responders agreed that, for most patients, ISR have only minimal impact on activities of daily living (AR: 3.48). Respond-ers recommended that patients should be advised to rotate injection

Background: Oligoclonal banding (OCB) detection in the cerebro-spinal fluid (CSF) is used as an indicator of multiple sclerosis (MS), as a majority of patients with clinically definite MS show oligoclonal IgG antibodies in their CSF. Lin et al. (2012) recently analyzed a sample population in Australia. The banding patterns of patients with positive OCB were found to have two novel distinct patterns named theta and delta. The theta pattern had no association with MS, and omission of the theta banding pattern improved the positive predic-tive value (PPV) of OCB testing for MS. It is uncertain if the theta and delta patterns have a similar correlation to MS in other populations, which highlights the need for further research in this area. Objec-tives: To confirm findings of theta and delta banding patterns and their association with a clinically definite diagnosis of MS through a retrospective study. To investigate if there are other subgroups of oli-goclonal banding patterns among patients with positive oligoclonal banding tests within the same population. Methods: Oligoclonal banding tests from patients of the Fraser Health MS Clinic in 2014 were observed with 15 positive CSF samples identified. Tests with comments of “weak positive OCB” were not included in the study. Correlating clinical information was collected. Additional tests from 2013 and 2012 will be studied. Band intensity and migration distance will be measured in all samples. Results: Of the 15 posi-tive CSF samples, 3 delta pattern and 1 theta pattern sample were omitted for pending diagnosis, leaving 11 positive CSF samples. 11 out of 11 (100%) samples positive for OCB were delta pattern, and 0 out of 11 (0%) were theta pattern. Of the 11 samples with delta pattern, 8 (73%) patients had clinically diagnosed MS, while there were no patients with the theta pattern. Full statistical analysis with additional results from 2012 and 2013 is in process. Conclusions: Frequency of the delta pattern to a diagnosis of MS was similar to that found by Lin et al. (2012), but since the samples analyzed were already narrowed to patients with a high suspicion of MS, this proportion may be lower, and therefore different from the frequency found by Lin et al. (2012). There were no samples with theta pattern, which questions the clinical use of determining theta and delta pat-terning in patients with a high suspicion of MS. A larger sample size and further study are needed to confirm these findings.

Supported by: Western-Pacific endMS Summer Studentship Award from the Multiple Sclerosis Society of Canada and the Multiple Sclerosis Scientific Research FoundationDisclosure: Kayleigh Da: Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Research Foundation (grant/research support). Jill R. Nelson, George Medvedev, Galina Vorobeychik: Nothing to disclose.Keywords: CSF oligoclonal banding

(DX56) SHARED DECISION MAKING IN MULTIPLE SCLEROSIS: LESSONS LEARNED FROM CREATING NEW DISEASE-MODIFYING THERAPY OPTION GRID DECISION SUPPORT TOOLSKaren Winn,1 Brant J. Oliver,1 Pamela Newland2

1School of Nursing, MGH Institute of Health Professions, Boston, MA; 2Nursing, Goldfarb School of Nursing, St. Louis, MA

Background: Option grids (OGs) are a type of online, concise decision support presented in a one-page grid format. They are developed using a bounded-rationality approach and are evidence-based, peer-reviewed, and patient-advised. OGs are used for prefer-ence-sensitive decisions in a shared decision-making approach in the clinical setting. No single disease-modifying therapy (DMT) has yet been identified as the optimal effective care treatment for all multiple sclerosis (MS) patients, making DMT decisions highly preference-sen-sitive. We recently created two OGs for DMTs in MS. Objectives: To describe the lessons learned during development of the OGs for DMT treatment in MS. Methods: The OGs were developed using a four-part process that included evidence synthesis of DMTs, review of OGs by an expert panel of MS clinicians and scientists, feedback from patient focus groups, and commentary by shared decision-making and decision science experts. In order to present a fair and

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Disclosure: Scott D. Newsome: Biogen Idec, Novartis (grant/research support); Biogen Idec, Genzyme, Novartis (consulting fees). Bernd C. Kieseier: Biogen, UCB, Novartis, Teva, Genzyme, Roche (consulting fees). Douglas L. Arnold: Acorda Therapeutics, Biogen Idec, Genzyme, Roche, Innate, Immunotherapeu-tics, MedImmune, Mitsubishi Pharma, Europe & Quintiles, Novartis, Receptos, Sanofi-Aventis, Teva, XenoPort (consulting fees); NeuroRx Research (ownership interest). Shulian Shang: Nothing to disclose. Serena Hung, Bjorn Sperling: Bio-gen Idec (salary).Keywords: Disease-modifying treatments in MS

(DX59) EFFECTS OF PEGINTERFERON BETA-1A ON VISUAL DYSFUNCTION IN MULTIPLE SCLEROSISScott D. Newsome,1 Laura J. Balcer,2 Shulian Shang,3 Shifang Liu,3 Serena Hung,3 Bjorn Sperling3

1Department of Neurology, Johns Hopkins University, Baltimore, MD; 2Department of Neurology, New York University, New York, NY; 3Biogen Idec Inc, Cambridge, MA

Background: Visual dysfunction is common in patients with relapsing-remitting multiple sclerosis (RRMS) and often accompa-nied by reduced quality of life. Although patients with RRMS often show similar scores to healthy volunteers on high-contrast (100% contrast) visual acuity tests, visual dysfunction is consistently seen when using low-contrast (eg, 2.5% contrast) visual acuity charts. Moreover, scores on low-contrast visual acuity correlate with physical and mental impairment. Here, Visual Function Test (VFT) scores were evaluated in the ADVANCE study. Objectives: To evaluate visual function changes in patients with RRMS treated with subcutaneous peginterferon beta-1a in the phase 3 ADVANCE study. Methods: ADVANCE was a 2-year, double-blind, placebo-controlled, phase 3 study in patients aged 18 to 65 years with RRMS. During year 1, patients were treated with peginterferon beta-1a 125 µg either every 2 weeks or every 4 weeks or placebo. At the end of year 1, patients on placebo were re-randomized to peginterferon beta-1a every 2 weeks or every 4 weeks (delayed treatment). At baseline and every 12 weeks during the study, patients were assessed for number of cor-rectly identified letters on the Low-contrast Sloan Letter Chart (out of 60 total) using the 1.25%, 2.5%, and 100% charts of the VFT. VFT changes at week 48 were compared between treated and placebo groups using an analysis of covariance model, adjusted for baseline VFT scores. Correlation analysis utilized the Spearman rank cor-relation. Results: In the subgroup of visually impaired patients with baseline 2.5% VFT scores below median, vision was significantly improved with peginterferon beta-1a every 2 weeks versus placebo at 48 weeks (2.4 vs. 1.1; P = .048 [2.5% VFT]). Overall popula-tion changes in 2.5% VFT scores from baseline to 48 weeks trended toward improvement in peginterferon beta-1a every 2 weeks versus placebo patients (0.2 vs. −0.5, P = .194). Across all patient groups at week 48, 2.5% VFT scores were significantly correlated with the Expanded Disability Status Scale (rho = −0.29), Multiple Sclerosis Impact Scale Physical Impact Scores (rho = −0.27) and Psychologi-cal Impact Scores (rho = −0.21), and the 12-Item Short Form Health Survey Physical Component Summary (rho = 0.26) and Mental Com-ponent Summary (rho = 0.19). Conclusions: In patients with RRMS with lower 2.5% VFT scores at baseline (below median), acuity was significantly improved following treatment with subcutaneous pegin-terferon beta-1a versus placebo.

Supported by: Biogen Idec IncDisclosure: Scott D. Newsome: Biogen Idec, Novartis (grant/research support); Biogen Idec, Genzyme, Novartis (consulting fees). Laura J. Balcer: Biogen Idec, Vaccinex, Genzyme (consulting fees). Shulian Shang, Shifang Liu, Serena Hung, Bjorn Sperling: Biogen Idec (salary).Keywords: Disease-modifying treatments in MS

(DX60) RELAPSE OUTCOMES IN PATIENTS WITH MULTIPLE SCLEROSIS TREATED WITH FINGOLIMOD AFTER PREVIOUS TREATMENT WITH INJECTABLE DISEASE-MODIFYING THERAPIESJacqueline Nicholas,1 Tobias Derfuss,2 Daniel Ontaneda,3 Xiangyi Meng,4 Kathleen Hawker4

site (AR: 3.83), cool the injection site after injection (AR: 3.10), and administer peginterferon beta-1a at room temperature (AR: 3.41) to manage ISR. All responders agreed that patients beginning treat-ment should be educated on the characteristics and management of FLS and ISR. Conclusions: The two-part Delphi questionnaire was successful in obtaining consensus on the characteristics and man-agement of FLS and ISR that can be associated with peginterferon beta-1a administration. Education should be provided to all patients before they begin treatment.

Supported by: Biogen IdecDisclosure: Scott D. Newsome: Biogen Idec, Novartis (grant/research support); Biogen Idec, Genzyme, Novartis (consulting fees). Diego Centonze: Almirall, Bayer Schering, Biogen Idec, Genzyme, GW Pharmaceuticals, Merck Serono, Novartis, Sanofi-Aventis, Teva (consulting fees); Bayer Schering, Biogen Idec, Novartis, Merck Serono, Sanofi-Aventis, Teva (grant/research support). DeRen Huang: Teva, Biogen Idec (consulting fees). June Halper: Biogen Idec (fees for non-CME services from commercial interests or their agents). Christopher Robert-son, Vladimir Evilevitch: Biogen Idec (ownership interest, salary). Xiaojun You, Guido Sabatella, Leslie Leahy: Biogen Idec (salary).Keywords: Disease-modifying treatments in MS, Management of activities of daily living in MS, Peginterferon

(DX58) PEGINTERFERON BETA-1A ADVANCE STUDY: SUBGROUP ANALYSIS OVER 2 YEARSScott D. Newsome,1 Bernd C. Kieseier,2 Douglas L. Arnold,3 Shulian Shang,4 Serena Hung,4 Bjorn Sperling4

1Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD; 2Department of Neurology, Heinrich-Heine University, Düsseldorf, Germany; 3Montreal Neurological Institute, McGill University, Montreal, QC, Canada; 4Biogen Idec Inc, Cambridge, MA

Background: ADVANCE was a 2-year, double-blind, placebo-con-trolled, phase 3 study in patients aged 18 to 65 years with relapsing-remitting multiple sclerosis (RRMS) that demonstrated that peginterfer-on beta-1a 125 µg administered subcutaneously every 2 or 4 weeks led to significant reductions in ARR compared with placebo. Objec-tives: To describe subgroup analyses of annualized relapse rate (ARR) over 2 years in the ADVANCE study. Methods: 1512 patients were treated with peginterferon beta-1a 125 µg every 2 weeks or every 4 weeks, or placebo during year 1. Thereafter, patients on pla-cebo were re-randomized to peginterferon beta-1a every 2 weeks or every 4 weeks (delayed treatment). Subgroup analyses (prespecified for year 1, repeated at year 2) were conducted by demographics (age, gender, weight, BMI, and geographic region) and baseline disease characteristics (number of prior relapses, time since most recent relapse, McDonald criteria, prior MS treatment, Expanded Disability Status Scale [EDSS], volume of T2 hyperintense lesions, and presence of gadolinium-enhancing [Gd+] lesions). The following results compared ARR in these subgroups for patients in continuous 2-week treatment with continuous 4-week treatment. Results: ARR was similar in most demographic and baseline disease character-istic subgroups evaluated within the peginterferon beta-1a every 2 weeks arm or every 4 weeks arm over 2 years. Although for both doses some differences in the point estimates for the ARR were noted among the subgroups, considerable overlap in the confidence inter-vals suggested that the efficacy of peginterferon beta-1a is similar in all patients irrespective of gender, age, body weight, geographic region, and disease activity at initiation of treatment. In some sub-groups analyzed (number of relapses in prior 3 years = 3, time since most recent relapse ≤ median, McDonald criteria of 1, EDSS < 4, no prior MS treatment, Gd+ lesions absent, T2 lesion volume < median, female, age < 40 years), ARR reduction reached signifi-cance in subjects treated with peginterferon beta-1a every 2 weeks compared with peginterferon beta-1a every 4 weeks. Conclusions: Within each peginterferon beta-1a dosing group, ARR was generally similar across most subgroups. Further, peginterferon beta-1a every 2 weeks demonstrated significant reductions in ARR versus peginter-feron beta-1a every 4 weeks in some subgroups tested.

Supported by: Biogen Idec Inc

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from the immune system. 3) They have a pronounced effect in recep-tor signaling (eg, arachidonate is used by the glutamate receptor to transfer signals inside the cell). 4) They play fundamental roles in the inflammatory response (eg, the lipid PGE2 is generated under stress and hypoxia). Objectives: Not applicable. Methods: Not appli-cable. Results: We have shown that the CPT1 agonist etomoxir has a dual mode of action. First, it blocks lipid metabolism, and second, it downregulates the immune response. Treatment with etomoxir of experimental autoimmune encephalomyelitis (EAE) in a therapeutic relevant setting, with treatment starting 10 days after disease induc-tion, reveals reversal of the disease outcome and repair of the myelin sheath pathology. In total, over 50% of the animals were disease-free after 2 weeks of treatment. In major support of the in vitro and in vivo experiments in rodents, it has recently been shown that individuals who have mutations in CPT1a (the target of etomoxir) are protected from developing MS among other CNS diseases. The mutation in CPT1a makes the efficacy of the CPT1a protein only 25% of the wild-type CPT1a. Where people in the same communities have an MS frequency of 1 in 350, no MS case was seen in the people carrying the mutation. Current studies are focused to elucidate in more detail the mode of action of etomoxir, and based on this new dual mode of action try to identify biomarkers for the different types of MS. Phase 2 clinical trials are under way using etomoxir in clinical studies in acute optic neuritis (as a pre-stage of MS) as well as in SPMS. Conclu-sions: This new dual mode of action approach is highly effective following a new way of thinking for MS development, progression, and treatment.

Supported by: NoneDisclosure: John D. Nieland, Jette G.K. Nieland: Meta-IQ (ownership interest). Soeren Nielsen: Nothing to disclose.Keywords: CNS repair, Complementary/alternative therapies in MS, Immunol-ogy and MS

(DX62) RELAPSE OUTCOMES IN PATIENTS TREATED WITH FINGOLIMOD ACCORDING TO DISEASE DURATIONDaniel Ontaneda,1 Tobias Derfuss,2 Jacqueline Nicholas,3 Xiangyi Meng,4 Kathleen Hawker4

1Neurological Institute–Mellen Center, Cleveland Clinic, Cleveland, OH; 2Department of Neurology, University Hospital Basel, Basel, Switzerland; 3The Ohio State University Multiple Sclerosis Center, Columbus, OH; 4Novartis Pharmaceuticals Corporation, East Hanover, NJ

Background: In phase 3 clinical trials, fingolimod significantly reduced annualized relapse rates (ARRs) in patients with relapsing-remitting multiple sclerosis (RRMS) in comparison with placebo and intramuscular interferon beta-1a (IFNβ-1a). This post hoc subgroup analysis of pooled data from the FREEDOMS, FREEDOMS II, and TRANSFORMS patient populations investigated the efficacy of fingoli-mod in subgroups with varying duration either of disease or of previ-ous exposure to disease-modifying therapies (DMTs). Objectives: To report the effects of oral fingolimod treatment on ARRs in patients with RRMS according to disease duration and duration of treatment with previous DMTs. Methods: Patient subgroups were defined by time since first symptom (≥3 vs. <3 years before randomization) and number of years of previous treatment (0, ≤1, >1–3, and >3 years before randomization). Results: In patients with less than 3 years since first symptom, fingolimod 0.5 mg significantly reduced ARR by 69% (ARR ratio: 0.31, n = 163, P < .001) versus placebo and by 50% (ARR ratio: 0.50, n = 140, P = .002) versus IFNβ-1a. In patients with 3 or more years since first symptom, reductions in ARR were 49% (ARR ratio: 0.51, n = 610, P < .001) versus placebo and 46% (ARR ratio: 0.54, n = 291, P < .001) versus IFNβ-1a. Fingo-limod 0.5 mg significantly reduced ARR in patients with 0, >1–3, and more than 3 years of treatment before randomization compared with placebo and IFNβ-1a, but not in patients in the IFNβ-1a group previously treated for 1 year or less (relative reduction: 35% [ARR ratio: 0.65, n = 64, P = .108]). Conclusions: Fingolimod 0.5 mg demonstrated consistent efficacy benefits over placebo and IFNβ-1a

1The Ohio State University Multiple Sclerosis Center, Columbus, OH; 2Department of Neurology, University Hospital Basel, Basel, Switzerland; 3Neurological Institute–Mellen Center, Cleveland Clinic, Cleveland, OH; 4Novartis Pharmaceuticals Corporation, East Hanover, NJ

Background: In phase 3 clinical trials, fingolimod significantly reduced annualized relapse rates (ARRs) in patients with relapsing-remitting multiple sclerosis (RRMS) in comparison with placebo and intramuscular interferon beta-1a (IFNβ-1a). This post hoc subgroup analysis of pooled data from the FREEDOMS, FREEDOMS II, and TRANSFORMS patient populations investigated the efficacy of fin-golimod in individuals with suboptimal response to previous disease-modifying therapies (DMTs). Objectives: To assess the effects of oral fingolimod treatment on ARRs in patients with RRMS who were naïve to previous treatment with IFNβ-1a or glatiramer acetate (GA) or had discontinued previous treatment with these agents. Methods: Subgroups included patients who had received injectable treatment for MS before study entry (IFN vs. IFN-naïve, GA vs. GA-naïve). Further subgroups were defined by reasons for discontinuation of previous treatment (unsatisfactory therapeutic effect vs. other reasons, and adverse event [AE] vs. other reasons). Results: Compared with placebo and IFNβ-1a, fingolimod 0.5 mg significantly reduced ARRs in patients who were IFN-naïve (relative reductions: 59%, n = 449; and 42%, n = 225, respectively; both P < .001), had previously received IFN (49%, n = 324; and 49%, n = 206, respectively; both P < .001), were GA-naïve (58%, n = 583; and 46%, n = 365, respectively; both P < .001), had previously received GA (42%, n = 190, P < 0.001; and 44%, n = 66, P = .015, respectively), had previously discontinued DMT owing to unsatisfactory therapeu-tic effect (54%, n = 112, P < 0.001; and 53%, n = 45, P = .009, respectively), and had previously discontinued DMT owing to an AE (37%, n = 222, P = .002; and 36%, n = 50, P = .090, respectively). Conclusions: Fingolimod 0.5 mg demonstrated consistent efficacy benefits over placebo and IFNβ-1a in patients with RRMS, regardless of previous therapy or reasons for discontinuing previous therapy.

Supported by: Novartis Pharmaceuticals CorporationDisclosure: Jacqueline Nicholas: National Multiple Sclerosis Society, Biogen Idec, National Institutes of Health, Actelion Pharmaceuticals, Mallinckrodt Phar-maceuticals, Roche, Novartis Pharmaceuticals Corporation, Genzyme, Vindico Medical (consulting fees). Tobias Derfuss: Novartis Pharmaceuticals Corporation, Merck Serono, Biogen Idec, GeNeuro, Genzyme, Mitsubishi Pharma, Teva Phar-maceuticals, Bayer Schering Pharma, European Union, Swiss National Founda-tion, Swiss MS Society (consulting fees). Daniel Ontaneda: National Institutes of Health, National Multiple Sclerosis Society, Acorda Therapeutics, Biogen Idec, Novartis Pharmaceuticals Corporation, Genzyme, QuestCor (consulting fees). Xiangyi Meng, Kathleen Hawker: Novartis Pharmaceuticals Corporation (salary).Keywords: Annualized relapse rate, Fingolimod, Patient subgroups

(DX61) CPT1 INHIBITOR SIGNIFICANTLY INDUCES REMYELINATION AND NEUROPROTECTION IN MULTIPLE SCLEROSIS BY A DUAL MODE OF ACTIONJohn D. Nieland,1 Jette G.K. Nieland,2 Soeren Nielsen1

1Health Science and Technology, Aalborg University, Aalborg, Denmark; 2Meta-IQ ApS, Aarhus, Denmark

Background: Multiple sclerosis (MS) is a complex disease that has been regarded as an inflammatory disease. However, all treatments based solely on the inflammatory response have not been effective in treating MS. In relapsing-remitting MS (RRMS) blockers of the inflammatory response can at best extend the time between relapses. In secondary progressive MS (SPMS) and primary progressive MS (PPMS) blockers of the inflammatory response have no effects. Recently new therapies targeted to block the downregulation of myelin protein production have not shown clinical efficacy. It is well established that the lipid levels and composition in MS patients are changed compared to healthy individuals. In addition, lipid metabo-lism has been shown to be upregulated. Lipids have quite a number of functions in the brain: 1) They are essential in functionally active myelin sheets (composed of myelin protein with lipids like palmitate coupled to it). 2) They shield the very immunogenic myelin protein

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nificant improvement in HRQOL was also found in the study group. However, these findings need to be corroborated in larger cohorts and for longer durations.

Disclosure: Nothing to discloseKeywords: Disease-modifying treatments in MS

(DX64) TOLERABILITY RESULTS FROM YEAR 1 OF THE PRISMS-2 2-YEAR RANDOMIZED CONTROLLED TRIAL OF INTERFERON BETA-1A SC TIW COMPARED WITH PLACEBOAmy Perrin Ross,1 Juanzhi Fang,2 Fernando Dangond2

1Loyola University Medical Center, Maywood, IL; 2EMD Serono, Inc, Rockland, MA

Background: In the PRISMS-2 study, interferon beta-1a (IFNβ-1a) 44 and 22 µg subcutaneously (SC) three times weekly (tiw) dem-onstrated significant efficacy compared with placebo in patients with relapsing-remitting multiple sclerosis (RRMS). Tolerability results indicated that flu-like symptoms (FLS) were common in all groups, and injection-site reactions (ISRs) during the first 3 months of therapy were common for IFNβ-1a SC, with no apparent difference between doses. Objectives: To evaluate tolerability data over 1 year from PRISMS-2 at incremental time periods and by severity, in order to further characterize the safety profile of IFNβ-1a SC tiw. Methods: In the PRISMS-2 study, 560 patients with ≥2 relapses over 2 years and Expanded Disability Status Scale score of 0–5.0 were randomly assigned to IFNβ-1a 44 or 22 µg SC tiw or placebo for 2 years. These post hoc analyses evaluated the frequency and severity of adverse events (AEs; eg, ISRs and FLS) at incremental time periods over 1 year (0–3, 3–6, and 6–12 months) and the rate of AEs leading to discontinuation. Results: Over 12 months, treatment-emergent AEs leading to discontinuation were rare and exceeded 1% incidence only for ISRs in the IFNβ-1a 44 µg SC tiw group. More patients receiving IFNβ-1a 44 or 22 µg SC versus placebo experi-enced ISRs over 12 months; no significant differences were observed for FLS. ISRs predominantly occurred over 0–3 months for IFNβ-1a 44 (31.5% [58/184]) or 22 (30.2% [57/189]) µg SC versus pla-cebo (5.9% [11/187]) and decreased thereafter from 3–6 months (IFNβ-1a 44 [3.8%] or 22 [1.6%] µg SC vs. placebo [1.1%]) and 6–12 months (IFNβ-1a 44 [3.8%] or 22 [1.1%] µg SC vs. placebo [0.5%]). FLS also predominantly occurred over 0–3 months (IFNβ-1a 44 [29.3%] or 22 [23.8%] µg SC vs. placebo [18.7%]) and decreased from 3–6 months (IFNβ-1a 44 [8.7%] or 22 [4.8%] µg SC vs. placebo [6.4%]) and 6–12 months (IFNβ-1a 44 [9.2%] or 22 [7.9%] µg SC vs. placebo [8.0%]). These AEs were predominantly mild or moderate: over 12 months, 1.6% of IFNβ-1a 22 µg SC patients had severe FLS, and 1.6% and 1.1% of IFNβ-1a 44 and 22 µg SC patients, respectively, had severe ISRs. Conclusions: There was a steep decline in the incidence of AEs after the first 3 months of IFNβ-1a SC tiw therapy. Over 1 year, most ISRs and FLS were mild.

Supported by: EMD Serono, Inc, a subsidiary of Merck KGaA; Pfizer IncDisclosure: Amy Perrin Ross: Biogen, EMD Serono, Pfizer, Bayer HealthCare, Teva, Genzyme, Novartis, Questcor, Acorda (speakers’ bureau); EMD Serono, Pfizer, Bayer HealthCare, Teva, Genzyme, Novartis, Questcor, Acorda (consult-ing fees). Juanzhi Fang, Fernando Dangond: EMD Serono, Inc, a subsidiary of Merck KGaA (salary).Keywords: Disease-modifying treatments in MS, Interferon beta

(DX65) PATIENT SATISFACTION WITH THE BETACONNECT AUTOINJECTOR FOR INTERFERON BETA-1BTjalf Ziemssen,1 Lauren Sylvester,2 Mark Rametta,2 Ivonne Weller,3 Julika Vogelreuter,3 Anna Saake,3 Thomas Schreiner,3 Nicolas Petroff,4 Amy Perrin Ross5

1Center for Clinical Neurosciences, Department of Neurology, University Hospital Carl Gustav Carus at the Technical University of Dresden, Dresden, Germany; 2Bayer HealthCare Pharmaceuticals, Whippany, NJ; 3Bayer Vital GmbH, Leverkusen, Germany; 4Vitartis Medizin-Service GmbH, Göttingen, Germany; 5Loyola University Medical Center, Maywood, IL

Background: Treatment of multiple sclerosis (MS) requires long-term use of disease-modifying therapies, which usually require regu-lar injections. Use of an autoinjector may reduce the discomfort of

in patients with RRMS, irrespective of time since first symptom or num-ber of years of previous treatment, with the exception of patients in the IFNβ-1a subgroup previously treated for 1 year or less.

Supported by: Novartis Pharmaceuticals CorporationDisclosure: Daniel Ontaneda: National Institutes of Health, National Multiple Sclerosis Society, Acorda Therapeutics, Biogen Idec, Novartis Pharmaceuticals Corporation, Genzyme, QuestCor (consulting fees). Tobias Derfuss: Novartis Pharmaceuticals Corporation, Merck Serono, Biogen Idec, GeNeuro, Genzyme, Mitsubishi Pharma, Teva Pharmaceuticals, Bayer Schering Pharma, European Union, Swiss National Foundation, Swiss MS Society (consulting fees). Jacqueline Nicholas: National Multiple Sclerosis Society, Biogen Idec, National Institutes of Health, Actelion Pharmaceuticals, Mallinckrodt Pharmaceuticals, Roche, Novar-tis Pharmaceuticals Corporation, Genzyme, Vindico Medical (consulting fees). Xiangyi Meng, Kathleen Hawker: Novartis Pharmaceuticals Corporation (salary).Keywords: Annualized relapse rate, Fingolimod, Patient subgroups

(DX63) EFFECTS OF MONTHLY PULSE METHYLPREDNISOLONE THERAPY ON SUSTAINED DISEASE PROGRESSION IN SECONDARY PROGRESSIVE MULTIPLE SCLEROSISSerkan Ozakbas,1 Bilge Piri Cinar,2 Gorkem Kosehasanogullari,3 Turhan Kahraman4

1Department of Neurology, Dokuz Eylul University, Izmir, Turkey; 2Giresun State Hospital, Giresun, Turkey; 3Usak State Hospital, Usak, Turkey; 4School of Physical Therapy and Rehabilitation, Dokuz Eylul University, Izmir, Turkey

Background: Most patients with multiple sclerosis (MS) initially experience a relapsing-remitting clinical course. Over years, patients who initially experience exacerbations may experience gradual progression of disability that occurs between or in the absence of exacerbations. This is known as the secondary progressive phase of MS (SPMS). Although there is agreement that corticosteroids often shorten the duration of acute exacerbations, a convincing therapeutic effect on sustained progression of disability has never been dem-onstrated in SPMS. Objectives: In the present study, we aimed to evaluate the efficacy of monthly pulse methylprednisolone treatment, especially on sustained progression of disability in SPMS patients. Methods: SPMS patients receiving no ongoing treatment or any treatment such as immunosuppressants (eg, azathiopirin), interferons, or glatiramer acetate (GA) were eligible if they had Expanded Dis-ability Status Scale (EDSS) scores of 3.0 or higher, and if they had at least 0.5-point sustained EDSS progression within the previous year. Patients with at least one relapse and new T2 or gadolinium-enhancing lesion within the previous year were also included in the study. Patients received 1 g pulse intravenous methylpredniso-lone (IVMP) once a month for at least 1 year. Outcomes included sustained EDSS progression (primary), relapse rate, and Multiple Sclerosis International Quality of Life (MUSIQoL) scores. Results: A total of 94 SPMS patients were included in the study. 91 patients (62 female) finished the 1-year study period. The mean age was 46.06 years, and the mean disease duration was 15.7 years. 60 patients were receiving azathiopirin, 3 patients were treated with interferon beta-1a (three times weekly), 2 patients with interferon beta-1b, and 2 patients with GA. 24 patients had no treatment at the beginning of the study. Mean EDSS score was decreased significantly from 5.75 ± 1.02 (3.0–8.0) to 5.41 ± 1.12 (3.0–7.5) (P = .000). 70 out of 91 (76.9%) patients had the same EDSS at the end of the study. 15 (16.5%) patients were less disabled. Only 6 patients had sustained EDSS (disease) progression at the end of the study year. Relapse rate was decreased from 0.5/year to 0.2/year (P = .011). As part of the inclusion criteria, there were no relapse-free plus progression-free patients before the study. However, at the end of the study, 83 (91.2%) patients had become relapse- and progression-free. There was no gender difference in terms of disability or relapse. There was no significant difference between patients with ongoing treatment and those with no ongoing treatment. Health-related quality of life (HRQOL) measured by MUSIQoL was significantly improved in the study population (P = .007). Conclusions: Our data suggested that methylprednisolone given in pulses every 4 weeks in SPMS leads to a significant reduction in disease progression and relapse rate. Sig-

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were re-randomized 1:1 to DMF 240 mg BID or TID. Adverse events (AEs) were analyzed according to treatment received in the parent/extension study: BID/BID (n = 501), TID/TID (n = 501), PBO/BID (n = 249), PBO/TID (n = 248), GA/BID (n = 118), and GA/TID (n = 119). Results: As of May 14, 2014, total follow-up in ENDORSE for all groups was 4981 patient-years. Overall incidence of AEs was as follows: BID/BID, 91%; TID/TID, 92%; PBO/BID, 95%; PBO/TID, 93%; GA/BID, 88%; and GA/TID, 85%. MS relapse and nasophar-yngitis were the most common AEs in patients continuing DMF; MS relapse and flushing were most common in those new to DMF. Flush-ing and gastrointestinal-related events were more common among patients new to DMF. Incidence of serious AEs (SAEs) was as follows: BID/BID, 22%; TID/TID, 25%; PBO/BID, 24%; PBO/TID, 16%; GA/BID, 16%; and GA/TID, 19%. The most common SAE was MS relapse; other individual SAEs occurred in no more than five patients in any treatment arm. Incidence of AEs leading to discontinuation was 6% to 7% and 14% to 26% in patients continuing and new to DMF, respectively. Incidence of serious infections was ≤4% in all groups, with no confirmed opportunistic infections.* There were no new findings in hematologic outcomes compared with DEFINE and CONFIRM. Hepatic AEs occurred in ≤3% of patients in any group; there was no evidence of increased risk of renal or urinary events. There were 27 malignancies in 26 patients (18 continuing treatment and 8 new to DMF). There were five deaths, none of which was considered related to study drug. Conclusions: Sustained treatment with DMF continues to demonstrate a favorable benefit:risk profile.*Note: After the May 2014 data cut, a case of progressive multifo-cal leukoencephalopathy was reported in the setting of severe, prolonged lymphopenia (approximately <0.5 × 109/L of 3.5 years’ duration).

Supported by: Biogen Idec, IncDisclosure: J. Theodore Phillips: Acorda, Biogen Idec, Genzyme, Merck Serono, Sanofi (consulting fees); Roche (grant/research support). Robert J. Fox: Actelion, Biogen Idec, Novartis (advisory committees, fees for non-CME services from com-mercial interests or their agents); Actelion, Biogen Idec, MedDay, Novartis, Quest-cor, Teva, XenoPort (consulting fees); Novartis (grant/research support). Krzysztof W. Selmaj: Biogen Idec, Inc (fees for non-CME services from commercial interests or their agents); Genzyme, Novartis, Ono, Roche, Synthon, Teva (consulting fees). Carlo Pozzilli: Actelion, Biogen Idec, Genzyme, Merck Serono, Novartis, Teva Neuroscience (consulting fees); Biogen Idec, Merck Serono, Novartis, Teva Neuro-science (grant/research support). Ray Zhang, Mark Novas, Marianne T. Sweetser: Biogen Idec, Inc (salary). Ralf Gold: Bayer HealthCare, Biogen Idec, Genzyme, Merck Serono, Novartis, Teva Neuroscience (grant/research support); Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, Teva Neuroscience, Genzyme (consulting fees); Sage, as editor of Therapeutic Advances in Neurological Disor-ders (editor compensation).Keywords: Disease-modifying treatments in MS

(DX67) USE OF A DELPHI PROCESS TO GAIN CONSENSUS ON EFFECTIVE MANAGEMENT OF GASTROINTESTINAL SIDE EFFECTS ASSOCIATED WITH DELAYED-RELEASE DIMETHYL FUMARATEJ. Theodore Phillips,1 April Erwin,2 Stephanie Agrella,3 Marcelo Kremenchutzky,4 John Kramer,5 Jonathan Kendter,6 Heather Abourjaily,7 Jitesh Rana,7 Robert J. Fox8

1Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, TX; 2The NeuroMedical Center Clinic, Baton Rouge, LA; 3Clinical Services, Multiple Sclerosis Clinic of Central Texas, Round Rock, TX; 4Western University and London Health Sciences Centre, London, ON, Canada; 5Center for Neurological Disorders, Milwaukee, WI; 6Biogen Idec, Weston, MA; 7Biogen Idec, Cambridge, MA; 8Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH

Background: Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) 240 mg twice daily is approved for patients with relapsing-remitting multiple sclerosis (RRMS). Gas-trointestinal (GI) side effects, especially in the first month of therapy, are an acknowledged accompaniment in some patients treated with DMF. Objectives: To use a Delphi consensus-building method to reach consensus on effective real-world management of GI events in patients receiving DMF. Methods: Clinicians in the United States and Canada treating MS patients with DMF were asked to complete

injections, increase patient satisfaction with treatment, and potentially increase adherence. BETACONNECT is an electronic autoinjector for interferon beta-1b (IFNβ-1b), developed to allow patients to custom-ize their injections with an ergonomic design that helps them access difficult-to-reach sites. Objectives: To assess patient satisfaction with BETACONNECT. Methods: A survey was conducted in Germany to evaluate satisfaction among patients on IFNβ-1b using BETACON-NECT. The importance of its features was also evaluated. A second survey is currently under way to further evaluate the impact of BETA-CONNECT on the patient’s injection experience. Final results of the second survey will be presented. Results: Invitations for the first survey were sent to 2299 users, and 1365 responded. Most (62%) were 40 to 59 years old. 50% had been treated with IFNβ-1b for >5 years. 69% were women and 21% were men, with 10% leaving this question unanswered. 48% had been using BETACONNECT for >2 months, 38% for 1–2 months, and 11% for <1 month, while 3% did not answer this question. 92% of patients reported the autoinjector to be “very helpful” or “helpful,” with little difference due to sex or the length of time on IFNβ-1b therapy. 88% rated the autoinjector as “excellent/good,” while 89% would likely recommend BETA-CONNECT to another patient. Of the 11 specific features that were addressed, all were rated as either “very important” or “important.” Features that were rated as “very important” included the electronic injection process, adjustable injection depth/speed, skin sensor, LED display, optical and acoustic signals, and rechargeable battery. The ergonomic design, invisible needle, and reminder function were rated “important.” Results of the second survey will also be present-ed. Conclusions: Overall patient satisfaction with BETACONNECT in the initial quantitative survey was high, with the majority rating the autoinjector as excellent and most features as very important. These findings suggest the use of BETACONNECT may help to increase sat-isfaction with treatment among patients on IFNβ-1b therapy.

Disclosure: Tjalf Ziemssen: Bayer HealthCare, Biogen Idec, Genzyme, MSD, GSK, Novartis, Teva, Sanofi, Almirall (fees for non-CME services from commer-cial interests or their agents); Bayer HealthCare, Biogen Idec, Genzyme, Novartis, Teva, Sanofi (grant/research support); Bayer HealthCare, Biogen Idec, Novartis, Merck Serono, Teva, Genzyme, Synthon (consulting fees). Lauren Sylvester, Mark Rametta: Bayer HealthCare Pharmaceuticals (salary). Ivonne Weller, Julika Vogelreuter: Bayer Vital GmbH (salary). Anna Saake: Bayer Vital GmbH (student apprentice). Thomas Schreiner: Bayer Vital GmbH (ownership interest, salary). Nicolas Petroff: Vitartis Medizin-Service GmbH (salary). Amy Perrin Ross: Acorda Therapeutics, Biogen Idec, EMD Serono, Inc, Novartis, Pfizer, Inc, Teva (fees for non-CME services from commercial interests or their agents); Acorda Therapeutics, EMD Serono, Inc, Genzyme Corporation, Novartis, Teva (consult-ing fees).Keywords: Disease-modifying treatments in MS, Equipment in MS, MS and the caregiver/family

(DX66) LONG-TERM FOLLOW-UP OF THE SAFETY OF DELAYED-RELEASE DIMETHYL FUMARATE IN RELAPSING-REMITTING MULTIPLE SCLEROSIS: INTERIM RESULTS FROM THE ENDORSE EXTENSION STUDYJ. Theodore Phillips,1 Robert J. Fox,2 Krzysztof W. Selmaj,3 Carlo Pozzilli,4 Ray Zhang,5 Mark Novas,5 Marianne T. Sweetser,5 Ralf Gold6

1Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, TX; 2Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH; 3Medical University of Lodz, Lodz, Poland; 4Faculty of Medicine, Sapienza University of Rome, Rome, Italy; 5Biogen Idec, Inc, Cambridge, MA; 6St. Josef Hospital, Ruhr University, Bochum, Germany

Background: Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) demonstrated broad efficacy and an accept-able safety profile in the phase 3 DEFINE and CONFIRM studies. ENDORSE is an 8-year extension of DEFINE and CONFIRM. Objec-tives: To report safety outcomes from ENDORSE, investigating long-term effects of DMF in patients with relapsing-remitting multiple scle-rosis (RRMS). Methods: Patients randomized to DMF 240 mg twice (BID) or three times daily (TID) in DEFINE or CONFIRM continued on the same dosage in ENDORSE. Patients randomized to placebo (PBO; DEFINE/CONFIRM) or glatiramer acetate (GA; CONFIRM)

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fied in both datasets. Logistic regression was used to study TXM-MS patient demographic and clinical characteristics associated with DMT utilization. Results: A total of 894 TXM-MS patients met the study criteria. The mean age of patients was 45 years (SD 11.9), 80% were female, and 38% were white. Less than half of MS patients (TXM: 49%, MM5: 43% of 3476) had Medicaid claims for DMTs during 2013. Compared to the MM5 sample, TXM-MS patients were older (45 vs. 42 years) and sicker (Charlson Comorbidity Index: 1.6 vs. 1), and a greater proportion was Hispanic (21% vs. 1%). Among TXM-MS patients, compared to those aged 50 to 59 years: those >60 years had lower odds of having DMT claims (OR: 0.544; 95% confidence interval [CI]: 0.359-0.823), those <40 years had greater odds (<30, OR: 2.572, 95% CI: 1.705-3.878) (30–39, OR: 1.424, 95% CI: 1.035-1.959), and those 40 to 49 years showed no differ-ence. Among TXM-MS patients, the odds of having DMT claims were lower for fee-for-service compared to managed-care patients (OR: 0.184, 95% CI: 0.140-0.240), and for sicker patients compared to their healthier counterparts (OR: 0.893; 95% CI: 0.838-0.951). Conclusions: Similar to the results using the MM5 database, less than half of the non-dual-eligible, nonelderly TXM-MS patients had Medicaid claims for DMTs. Follow-up studies are warranted to inves-tigate the reasons for the absence of DMT claims among a large proportion of Medicaid patients.

Supported by: Novartis PharmaceuticalsDisclosure: Kristin M. Richards: Novartis (grant/research support). Kenneth A. Lawson: Nothing to disclose. Tara A. Nazareth, Tzy-Chyi Yu, Rahul Sasane: Novartis Pharmaceuticals (salary, ownership interest). Huanxue Zhou: KMK Consulting Inc (salary). Erik Burton: Novartis (salary).Keywords: Disease-modifying treatments in MS

(DX70) A COMPREHENSIVE ANALYSIS OF RELAPSE IN MULTIPLE SCLEROSISEmily S. Riser,1 Jian Han,2 Thomas Denney,3 Miranda B. Steele2

1Tanner Center for MS, Birmingham, AL; 2HudsonAlpha Institute for Biotechnology, Huntsvillle, AL; 3Auburn University, Auburn, AL

Background: The neurosciences have ushered in an era of astounding discovery. Yet there is still much to learn about the com-plexities of neurologic diseases, especially multiple sclerosis (MS). Therefore, the Tanner Center for MS formed an alliance with the HudsonAlpha Institute of Biotechnology and Auburn University utiliz-ing 7T imaging. Our specific purpose was to apply immunogenomic analysis and advanced imaging of documented clinical MS relapses treated with 14 days of Acthar gel. Objectives: The purpose of the study is to better understand the immunology, imaging metrics, and clinical outcomes of subjects treated with Acthar Gel administered for 14 days rather than the current 5-day treatment. Methods: This is an observational cohort study involving 20 subjects with relaps-ing forms of MS, seen within 72 hours of relapse onset. Baseline laboratory tests for immunogenomic analysis and 7T imaging are performed, followed by 14 days of Acthar gel. Additional labora-tory results are drawn at days 5,14, and 30. For immune repertoire analysis, peripheral blood mononuclear cells are purified using a Ficoll density gradient, and are then sorted into panB, panT, monocytes, T helper, regulatory T, and T cytotoxic cell populations. Cell-specific TCR beta and IgH variable region genes are amplified from extracted cellular RNA using amplicon-rescued-multiplex-PCR (arm-PCR) and are sequenced using Illumina next-generation sequenc-ing platforms. 7T imaging is performed at baseline and at day 30 utilizing T2 FLAIR, T1 MPRAGE, SWI, and T1 post contrast at 8,14, and 20 minutes. Results: Immunogenomic analysis has been com-pleted with VDJ rearrangements for six cell subsets covering four timepoints of five subjects (120 libraries) having been generated. The distribution of CDR3 sequences, corresponding to the T-cell and B-cell receptors, were examined for changes in overall diversity levels (D50 measurements), CDR3 length distribution, V- and J- usage frequen-cies, and N-addition and trimming to assess the effect of treatment on different cell subsets for the first five subjects. The qualitative magnetic

two rounds of questionnaires developed by the steering committee. Information from the first questionnaire was used to develop the sec-ond, which sought further clarification to achieve consensus (≥70% agreement) on management strategies for each type of GI event. Questions focused on the incidence and management of nausea, vomiting, abdominal pain, and diarrhea. Values reported represent the percentage of respondents who agreed with the specified man-agement strategy. Results: The first questionnaire was completed by 64 respondents and 57 completed the second; the majority (63/64 and 56/57, respectively) stated that ≥1 of their patients had expe-rienced a GI side effect with DMF. Consensus was reached on tak-ing DMF with food as a useful management strategy to reduce the incidence and/or severity of nausea (98%), vomiting (89%), and abdominal pain (93%). Respondents also agreed that slower DMF dose titration (>7 days to reach the approved maintenance dose) can be effective for reducing the incidence and/or severity of nausea (98%), vomiting (96%), abdominal pain (94%), and diarrhea (92%). Temporary DMF dose reduction was confirmed as a useful manage-ment strategy for reducing the impact of nausea (100%), vomiting (90%), abdominal pain (90%), and diarrhea (86%). Regarding spe-cific medications, consensus was reached on using antacids (73%), bismuth subsalicylate (71%), ondansetron (93%), or promethazine (71%) for nausea; bismuth subsalicylate (71%), ondansetron (93%) or promethazine (71%) for vomiting; antacids (75%), bismuth sub-salicylate (77%), H2 blockers (73%), or proton pump inhibitors (80%) for abdominal pain; and diphenoxylate/atropine (91%) or loper-amide (95%) for diarrhea. Conclusions: Clinicians with experience using DMF reached consensus on several potentially useful strategies to manage GI side effects, including administering DMF with food, slower titration, and use of symptomatic therapies.

Supported by: Biogen IdecDisclosure: J. Theodore Phillips: Acorda, Biogen Idec, Genzyme, Merck Serono, Sanofi (consulting fees); Roche (grant/research support). April Erwin: Novartis, Biogen Idec (consulting fees). Stephanie Agrella: Acorda, Biogen, Teva, Genzyme, Serono, Pfizer (consulting fees). Marcelo Kremenchutzky: Biogen, Sanofi, Gen-zyme, Novartis, Bayer, Teva, Serono (consulting fees, grant/research support). John Kramer: Biogen, Genzyme, Teva, Novartis (consulting fees); Biogen, Novartis, Genzyme (grant/research support). Jonathan Kendter, Heather Abourjaily, Jitesh Rana: Biogen Idec (salary, ownership interest). Robert J. Fox: Actelion, Biogen Idec, MedDay, Novartis, Questcor, Teva, XenoPort (consulting fees); Novartis (grant/research support).Keywords: Delphi technique; Health-care surveys; Dimethyl fumarate

(DX68) SEE PAGE 87

(DX69) MULTIPLE SCLEROSIS MEDICATION UTILIZATION IN TEXAS MEDICAIDKristin M. Richards,1 Kenneth A. Lawson,1 Tara A. Nazareth,2 Huanxue Zhou,3 Erik Burton,2 Tzy-Chyi Yu,2 Rahul Sasane2

1Center for Pharmacoeconomic Studies, The University of Texas at Austin, Austin, TX; 2US Health Economics and Outcomes Research, Novartis Pharmaceuticals Corporation, East Hanover, NJ; 3KMK Consulting, Inc, Florham Park, NJ

Background: Disease-modifying therapies (DMTs) provide relief to patients with multiple sclerosis (MS) through prevention and mitiga-tion of relapses and disease progression. Despite the availability of several DMTs, some patients do not use these medications. Research indicates that patients covered by Medicaid may be less likely to receive DMTs than those with Medicare or private insurance. As such, Medicaid patients with MS are an important group for study. Objectives: 1) Identify the demographic and clinical characteris-tics of Texas Medicaid (TXM) patients with MS (TXM-MS patients). 2) Compare these characteristics with those of MS patients from a combined five-state MarketScan Medicaid (MM5) claims database. 3) Determine the relationships between patient characteristics and the receipt of DMTs in TXM-MS patients. Methods: Medical and pre-scription data from the TXM and MM5 databases were used in this study. Non-dual eligible adults (18–64 years) with an MS diagnosis (ICD-9-CM = 340) and continuous eligibility in 2013 were identi-

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affecting the central nervous system through interaction between genetic predisposition and environmental factors. Objectives: Pres-ent a case in which aspartame exposure is temporally associated with MS relapse with significant inflammation on brain magnetic resonance imaging (MRI). Methods: Clinical and radiographic correlation of a patient presenting with an MS relapse. Results: A 35-year-old female with a 13-year history of relapsing-remitting MS presented with a relapse, including symptoms of right-sided numbness, falls/imbalance, poor spatial awareness, and anxiety/rage. She abstained from sugar for 2 weeks, heavily substituting aspartame as a sweetener before discontinuing aspartame due to neurologic symptom onset. She previously had six relapses over the first 11 years of MS, with resolution of symptoms after each episode. Examination revealed mild right interosseous and right iliopsoas weakness. The remainder of the neurologic exam was normal. Brain MRI demonstrated four active lesions. Brain MRI studies 6 months before, 2 months after, and 20 months after the relapse were stable in lesion burden and were inactive. She was on weekly interferon beta-1a; neutralizing antibodies were negative after the relapse. Her neurologic symptoms resolved after approximately 1 month. Conclu-sions: This case may represent aspartame influencing inflammation in a human with MS. The literature on aspartame studies in animal models and humans is discussed. The literature has conflicting points of view.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Environment and MS, Imaging and MS

(DX73) IMPROVEMENTS IN QUALITY OF LIFE ARE MAINTAINED IN ALEMTUZUMAB-TREATED RELAPSING-REMITTING MULTIPLE SCLEROSIS PATIENTS WHO DEVELOP AUTOIMMUNE ADVERSE EVENTS: CARE-MS IIBarry Singer,1 Gavin Giovannoni,2 Hans-Peter Hartung,3 David H. Margolin,4 Linda Kasten,5 Jeffrey A. Cohen6

1The MS Center for Innovations in Care, Missouri Baptist Medical Center, St. Louis, MO; 2Queen Mary University of London, Barts and The London School of Medicine, London, United Kingdom; 3Heinrich-Heine University, Düsseldorf, Germany; 4Genzyme, a Sanofi company, Cambridge, MA; 5PROMETRIKA, LLC, Cambridge, MA; 6Cleveland Clinic, Cleveland, OH

Background: In the phase 3 CARE-MS II trial (NCT00548405), alemtuzumab demonstrated superior efficacy and quality of life (QOL) improvements over subcutaneous interferon beta-1a (SC IFNβ-1a) in patients with relapsing-remitting multiple sclerosis (RRMS) and an inadequate efficacy response to prior therapy. Alemtuzumab’s consistent and manageable safety profile includes a risk of autoim-mune disorders, predominantly thyroid disorders, less frequently immune thrombocytopenia (ITP), and rarely nephropathies, includ-ing anti-glomerular basement membrane disease. Objectives: To evaluate whether the occurrence of autoimmune adverse events (AEs) reduces QOL improvements seen in RRMS patients who received alemtuzumab 12 mg over 2 years in CARE-MS II. Methods: In CARE-MS II, patients with ≥1 relapse after ≥6 months of prior therapy were randomized to either 2 annual courses of alemtuzumab 12 mg/day or SC IFNβ-1a 44 µg three times weekly. Stratified by the presence/absence of autoimmune AEs, QOL was assessed within the alemtuzumab group using the Short Form Health Survey (SF-36) Physical Component Summary (PCS; scale 1–100), the Functional Assessment of Multiple Sclerosis (FAMS; scale 0–176), and the EuroQol 5-dimension scale (EQ-5D) Visual Analog Scale (VAS; scale 0–100). The SF-36 Mental Component Summary was excluded from the analysis because there was no difference between alemtuzumab and SC IFNβ-1a at year 2. Monitoring for autoimmune AEs was performed at baseline and monthly (ITP; nephropathies) or quarterly (thyroid) through a comprehensive monitoring program. Results: Among alemtuzumab-treated patients, 17% (74 of 435) had auto-immune AEs during the 2-year controlled portion of CARE-MS II. At year 2, mean changes in QOL scores were similar in alemtuzumab

resonance imaging (MRI) analysis confirms that 7T imaging utilizing T2 FLAIR, T1 MPRAGE, and delayed contrast is robust in confirming both inflammation and axonal degeneration. Conclusions: Initial immunogenomic analysis and 7T MRI data of subjects who received Acthar gel for up to 14 days are presented. Notably, the regulatory T-cell subset shows a statistically significant decrease in D50 values after initial treatment and persisting through D14, indicating a clonal expansion in this important cellular subset. In addition, the initial MRI analysis indicates improved metrics in confirming an inflammatory response as well as secondary axonal degeneration. Identified trends will be reevaluated as more subject data become available.

Supported by: MallinckrodtDisclosure: Emily S. Riser: Biogen Idec, Teva (consulting fees). Jian Han, Thomas Denney, Miranda B. Steele: Nothing to disclose.Keywords: Imaging and MS, Immunology and MS

(DX71) PATIENT-REPORTED TREATMENT EXPERIENCE OF MULTIPLE SCLEROSIS PATIENTS RECEIVING DELAYED-RELEASE DIMETHYL FUMARATE FROM SPECIALTY PHARMACY: INTERIM RESULTSAlysha M. Robinson, Stephanie S. Holliday

Clinical Services, AcariaHealth, Orlando, FL

Background: While the clinical profile of delayed-release dimethyl fumarate (DMF) was established in the phase 3 clinical trials, few data exist to understand patient treatment experience in the real world. In December 2013, a national specialty pharmacy began a 12-month study of multiple sclerosis (MS) patients starting DMF. Objectives: To assess treatment experience of MS patients treated with DMF in the areas of patient-reported medication tolerability, medication adherence, and disease-related outcomes. Methods: This observational study collects patient-reported endpoints includ-ing the incidence of adverse events and proportion of unresolved adverse events, as well as adherence at predefined intervals (weeks 0, 1, 4, 8, 12, 24, 48, 72, 96) via clinician-administered telephonic surveys. As of 11/1/2014, 165 of 750 enrolled patients had completed endpoint collection at week 24. Results: Interim results as of 11/1/2014. Tolerability: At the week 1, 4, 8, 12, and 24 assessments, 24%, 27%, 17%, 19%, and 13% of patients reported unresolved adverse events, respectively. The most commonly reported adverse events include flushing, stomach/GI upset, diarrhea, and nausea. While most patients remained on therapy without modifica-tion, the rate of therapy modification (change in regimen) or discon-tinuation ranged from 1% to 7%. With the exception of the week 4 assessment, the combined therapy modification and discontinuation rate did not exceed 2% of patients. The most common management strategies by adverse event: 28% tried aspirin to control flushing, 25% tried antacid to control GI upset; 49% tried other remedy to control diarrhea, 30% tried an anti-emetic for nausea. Adherence: Although 31% of patients reported missing at least one dose in the first 4 weeks of therapy, only 7% reported missing more than 2 doses. Disease-Related Outcomes: As of 11/1/2014, there were five patient-reported hospitalizations related to relapse. Regarding ambu-lation, 25%, 26%, 25%, and 31% of patients reported requiring aid or assistance to walk or being unable to walk at weeks 4, 8, 12, and 24, respectively. Conclusions: To be determined.

Supported by: Biogen IdecDisclosure: Alysha M. Robinson: Biogen (consulting fees, grant/research support). Stephanie S. Holliday: Biogen (grant/research support).Keywords: Disease-modifying treatments in MS

(DX72) POTENTIAL ASSOCIATION OF ASPARTAME WITH MULTIPLE SCLEROSIS RELAPSELindsay A. Ross,1 Boyd M. Koffman2

1Neurology, University of Toledo College of Medicine, Toledo, OH; 2Neurology, University of Toledo Health Sciences Campus, Toledo, OH

Background: While the cause of multiple sclerosis (MS) is unknown, the consensus is that it is an immune-mediated disease

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(DX75) DEVELOPMENT OF CHRONIC BLACK HOLES PREDICTS LONG-TERM DISABILITY: POST HOC ANALYSIS OF MAGNETIC RESONANCE IMAGING DATA IN THE PRISMS STUDYAnthony Traboulsee,1 David K. Li,1 Juanzhi Fang,2 Fernando Dangond2

1University of British Columbia, Vancouver, BC, Canada; 2EMD Serono, Inc, Rockland, MA

Background: Chronic black holes (CBH) indicate axonal loss in multiple sclerosis (MS), and may be associated with long-term disabil-ity progression. Objectives: Assess the effect of subcutaneous (SC) interferon beta-1a (IFNβ-1a) on evolution of gadolinium-enhancing (Gd+) lesions into CBH in patients with relapsing-remitting MS (RRMS) and the predictive value of CBH for long-term disability. Methods: Retrospective analysis of magnetic resonance imaging (MRI) scans of patients in the PRISMS study (RRMS; baseline Expanded Disability Status Scale [EDSS] score 0–5.0) who were randomized to IFNβ-1a, 44 or 22 µg three times weekly or placebo; after 2 years, placebo patients were re-randomized to IFNβ-1a 44 or 22 µg (delayed treat-ment [DT]). Patients with monthly scans from months −1 to 9 and ≥1 new enhancing lesions (NEL) from months −1 to 3 were included; CBH evolving from NEL were assessed at month 8/9. Association between CBH and disability outcome at 4 years’ follow-up was analyzed according to treatment group. Results: 196 patients were included (IFNβ-1a combined, n = 129; DT, n = 67). In the IFNβ-1a group, 73/129 (57%) had NEL from months −1 to 3 versus 49/67 (73%) in the DT group; ≥1 CBH at month 8/9 developed in 25/73 (34%) and 27/49 (55%) patients with ≥1 NEL, respectively. For patients who developed CBH (CBH+) a higher proportion (55.8%) experienced disability progression (confirmed 3-month Expanded Disability Status Scale [EDSS] progression rate at 4 years) than those who did not (CBH−, 43.1%). For CBH+ patients, proportions with confirmed EDSS progression at 1, 2, 3, and 4 years were DT 37.0%, 48.1%, 55.6%, and 59.3%, respectively; IFNβ-1a 12.0%, 32.0%, 52.0%, and 52.0%, respectively. Fewer CBH− patients showed confirmed EDSS progression at 1, 2, 3, and 4 years: DT 35.0%, 37.5%, 37.5%, and 45.0%, respectively; IFNβ-1a 21.2%, 29.8%, 39.4%, and 42.3%, respectively. For CBH+ patients, median EDSS score in the DT group increased from 2.0 at month 8/9 to 3.5 at 4 years; in the IFNβ-1a group, the score increased from 2.5 to 3.0. For CBH− patients, median EDSS scores at month 8/9 and 4 years were DT from 2.0 to 2.5 and IFNβ-1a from 2.0 to 2.0, respectively. Conclusions: CBH development in the first 9 months was associated with greater disability progression at 4 years, regardless of whether patients received treatment. However, treatment with SC IFNβ-1a was associated with a decreased proportion of NEL evolving into CBH, and slower progression of disability at 4 years.

Acknowledgments: Guojun Zhao, Yan Cheng, Andrew Riddehough (Univer-sity of British Columbia, Vancouver, BC, Canada) for their contributions to the analysisSupported by: Merck Serono SA, an affiliate of Merck KGaADisclosure: Anthony Traboulsee: Chugai Pharmaceuticals, EMD Serono, Merck Serono, Roche, Sanofi-Genzyme, Teva Canada Innovation (travel grants); Roche, Sanofi-Genzyme (grant/research support). David K. Li: EMD Serono, Genzyme, Roche (grant/research support); Genzyme, Novartis (consulting fees); Opeca, Nuron (advisory board member). Juanzhi Fang, Fernando Dangond: EMD Serono (employee).Keywords: Chronic black hole development

(DX76) PATIENT PERSPECTIVES ON INSURANCE CHANGES AND THERAPY DECISIONS IN NARCOMSStacey S. Cofield,1 Tuula Tyry,2 Amber R. Salter,1 Sandre McNeal,1 Robert J. Fox,3 Ruth Ann Marrie,4 Gary Cutter,1 Guoqiao Wang1

1Biostatistics, University of Alabama at Birmingham, Birmingham, AL; 2Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ; 3Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH; 4University of Manitoba, Winnipeg, MB, Canada

Background: Making treatment decisions for multiple sclerosis (MS) involves several factors, including insurance coverage and

patients with or without autoimmune AEs: FAMS (with autoimmune AEs, 8.9 [SE 3.3]; no autoimmune AEs, 5.9 [1.2]), PCS (with autoim-mune AEs, 2.7 [1.0]; no autoimmune AEs, 2.4 [0.4]), and EQ-5D VAS (with autoimmune AEs, 4.1 [2.0]; no autoimmune AEs, 3.7 [0.9]). In addition, mean (SE) changes in QOL scores from baseline in both subgroups were similar to the overall alemtuzumab cohort (FAMS, 6.7 [1.2]; PCS, 2.4 [0.4]; EQ-5D VAS, 3.6 [0.9]) and great-er than the SC IFNβ-a–treated group (FAMS, 1.8 [1.6]; PCS, 0.6 [0.6]; EQ-5D VAS, –0.9 [1.3]). Conclusions: QOL improvements were similar in alemtuzumab patients with or without autoimmune AEs; both subgroups had greater QOL improvements than patients treated with SC IFNβ-1a.

Supported by: Genzyme, a Sanofi company; Bayer HealthCare PharmaceuticalsDisclosure: Barry Singer: Acorda, Bayer, Biogen Idec, EMD Serono, Genzyme, Novartis, Pfizer, Teva (consulting fees). Gavin Giovannoni: AbbVie, Biogen Idec, Genzyme, GlaxoSmithKline, Merck, Merck-Serono, Novartis, Roche, Sanofi, Synthon BV, Teva (consulting fees). Hans-Peter Hartung: Bayer HealthCare, Bio-gen Idec, CSL Behring, Genzyme, Hoffmann-LaRoche, Novartis, Octapharma, Sanofi, Teva (consulting fees). David H. Margolin: Genzyme, a Sanofi company (salary). Linda Kasten: Genzyme, a Sanofi company (consulting fees). Jeffrey A. Cohen: EMD Serono, Genentech, Innate Immunotherapeutics, Vaccinex (consult-ing fees).Keywords: Alemtuzumab, Disease-modifying treatments in MS

(DX74) FINGOLIMOD FIRST-DOSE EFFECTS IN THE PREFERMS REAL-WORLD STUDY OF PATIENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSISNadia Tenenbaum, Xiangyi Meng, Lesley Schofield, Kathleen Hawker

Novartis Pharmaceuticals Corporation, East Hanover, NJ

Background: Fingolimod treatment initiation is associated with transient, typically asymptomatic bradycardia. Phase 3 study data have demonstrated that symptomatic bradycardia and atrioventricu-lar block (AVB) are uncommon and do not require intervention. Real-world evidence supports these findings. Objectives: To compare the first-dose effects of fingolimod in a real-world cohort of US patients with findings from pivotal phase 3 clinical studies. Methods: In the PREFERMS (Prospective, Randomized, active-controlled, open-label study to Evaluate patient retention of Fingolimod versus approved first-line disease modifying thErapies in adults with Relapsing-remitting Multiple Sclerosis) 12-month study, patients were either treatment-naïve or previously treated with interferon, glatiramer acetate, or dimethyl fumarate (<2-month exposure). Patients randomized to fingolimod 0.5 mg underwent electrocardiogram monitoring at baseline and 6 hours after first dose, with vital signs recorded hourly. This study provides descriptive comparisons with pooled data from FREEDOMS, FREEDOMS II, and TRANSFORMS patient popula-tions. Results: Baseline demographics in PREFERMS (n = 637) were generally consistent with those in pooled phase 3 studies (n = 1212), although a higher proportion of patients in PREFERMS had existing hypertension (15.7% and 7.8%, respectively). Consistent with phase 3 study findings, the lowest mean heart rate in PREFERMS was reached at 5 hours post-dose (mean change from baseline, –7.3 bpm) and began to recover by 6 hours. A similar proportion of patients experienced first-degree AVB in PREFERMS and phase 3 studies (5.6% and 4.7%, respectively), and the incidence of Mobitz I AVB was low in both analyses (0.5% and 0.2%, respectively). A higher proportion of patients in PREFERMS was discharged at 6 hours than in phase 3 studies (90.3% and 83.0%, respectively), fewer patients required extended monitoring after 6 hours (8.3% and 12.9%, respectively), and no patients discontinued on day 1. Patient subgroup analyses will be provided. Conclusions: The results of this real-world study were consistent with those of previous controlled fingolimod trials and confirmed the benign nature of fingolimod first-dose effects.

Supported by: Novartis Pharmaceuticals CorporationDisclosure: Novartis Pharmaceuticals Corporation (salary)Keywords: Fingolimod, First-dose effect, Multiple sclerosis

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Posters: Quality of Life Outcomes

QUALITY OF LIFE OUTCOMES

(QL01) PHYSICAL ACTIVITY, DIETARY SODIUM, AND SMOKING AS CORRELATES OF WALKING PERFORMANCE IN PEOPLE WITH MULTIPLE SCLEROSISJulia M. Balto, Jennifer L. Barnes, Ipek Ensari, Elizabeth A. Hubbard, Robert W. Motl


Background: There is increasing interest in studying the asso-ciation between modifiable health behaviors and clinical outcomes in people with multiple sclerosis (MS). Physical activity, dietary sodium intake, and smoking may be associated with walking performance as a clinical manifestation of MS. We are unaware of research analyzing the joint association of these three health behaviors with walking performance in MS. Objectives: This study examined the relationships of physical activity, dietary sodium intake, and smoking with walking performance after accounting for disability status as a covariate. Methods: Thirty-one community-dwelling participants with MS underwent neurologic examinations for generation of Expanded Disability Status Scale (EDSS) scores, followed by breath carbon monoxide (BCO) evaluation using the Bedfont Micro+ Smokerlyzer for assessment of smoking status (ppm). Participants completed the Timed 25-Foot Walk (T25FW) recorded in speed (feet/second) and 6-Minute Walk (6MW) recorded in distance (feet), and wore an accelerometer during the waking hours of a 7-day period to objectively measure physical activity as minutes/day of moderate-to-vigorous physical activity (MVPA). Participants completed a 24-hour urine collection following the protocol devel-oped by the National Center for Health Statistics for the National Health and Nutrition Examination Survey (NHANES) for a marker of dietary sodium intake (ppm). The data were analyzed using bivariate correlations and multiple linear regression (MLR) in SPSS Statistics 22.0. Results: MVPA was moderately correlated with 6MW (r = 0.50), T25FW (r = 0.47), and EDSS (r = −0.35). Dietary sodium intake was weakly correlated with 6MW (r = 0.16), T25FW (r = 0.17), and EDSS (r = −0.13). There was a moderate correlation between smoking and 6MW (r = −0.40), and a weak correlation with T25FW (r = −0.29) and EDSS (r = 0.32). MLR indicated that only MVPA explained a significant portion of variance in 6MW (ΔR² = 0.20, β = 0.48) and T25FW (ΔR² = 0.18, β = 0.45), after controlling for EDSS scores; dietary sodium intake and smoking did not explain variance in 6MW or T25FW. Conclusions: Physical activity was independently associated with walking performance. This suggests that increasing MVPA levels might be of greater value than decreasing salt consumption or smoking for improving clinical outcomes such as walking in MS.

Supported by: NoneDisclosure: Julia M. Balto, Jennifer L. Barnes, Ipek Ensari, Elizabeth A. Hub-bard: Nothing to disclose. Robert W. Motl: Biogen, Acorda (consulting fees, grant/research support); EMD Serono (fees for non-CME services from commercial interests or their agents).Keywords: Management of activities of daily living in MS, Physical activity

(QL02) BASELINE CHARACTERISTICS OF PATIENTS ENROLLED IN THE TERI-PRO PHASE 4 STUDY IN THE UNITED STATES VERSUS CANADA, EUROPE, AND LATIN AMERICAPatricia K. Coyle,1 Christopher LaGanke,2 Bhupendra Khatri,3 Ralf Gold,4 Steven Cavalier,5 Sandrine Brette,6 Francesca Baldinetti,5 Keith R. Edwards7

1Department of Neurology, Stony Brook University Medical Center, Stony Brook, NY; 2North Central Neurology Associates, Cullman, AL; 3The Regional MS Center, Center for Neurological Disorders at Wheaton Franciscan Healthcare, Milwaukee, WI; 4St. Josef-Hospital/Ruhr-University Bochum, Bochum, Germany; 5Genzyme, a Sanofi company, Cambridge, MA; 6Lincoln, Boulogne-Billancourt, France; 7Multiple Sclerosis Center of Northeastern New York, Latham, NY

Background: Teriflunomide is a once-daily oral immunomodula-tor that has shown consistent efficacy in phase 3 studies in patients

financial situation. Important changes to insurance coverage in the last few years may have required some patients to change their disease-modifying therapies (DMTs) for financial rather than clinical reasons. Objectives: To describe the insurance status of NARCOMS participants and how insurance and financial situation affects DMT choices. Methods: The NARCOMS Fall 2014 Update survey included questions about health insurance and DMT choices related to insurance: current health insurance (Yes/No), health insur-ance for the prior 6 months (Yes/No), comparison of current health insurance to 12 months prior (better, worse, unchanged), and how insurance/financial situation has influenced treatment of MS. Results shown represent only those registry participants who completed the survey online (data entry for paper forms is still ongoing). Results: Of the 5106 participants who completed the update online, 4507 (96.9%) completed the health insurance questions, 78.8% were female, with mean (SD) age of 56.7 (9.6) years, and 62.1% had relapsing-remitting MS (RRMS). Nearly all (99.5%) participants had health insurance. 98.6% had insurance for the prior 6 months, with 68.6% reporting insurance coverage had not changed in the prior year, while 23.0% reported worse coverage compared to 12 months ago. Coverage did not differ by gender or MS type, but more females reported their insurance coverage to be worse compared to 12 months ago (23.9% vs. 19.7%, P = .013). More respondents with progressive MS reported no change in coverage compared to RRMS (73.3% vs. 66.8%, P = .0003). When asked about influence of insurance or financial situation on DMT choice, 30.0% reported not taking DMT by choice or physician recommendation; 15.9% reported taking their DMT of choice with full coverage; 46.6% report-ed taking their DMT of choice with a copay; 19.1% reported taking their DMT of choice with a free/discounted drug program; 3.6% reported being able to switch DMTs with insurance approval; 1.3% reported wanting to switch but not being able to due to lack of insur-ance approval/coverage; 2.4% reported having to stop/change/skip DMTs due to higher copays; and 1.6% reported not taking DMTs because they did not have insurance or insurance denied the DMT. Conclusions: Most participants did not perceive major impacts on their insurance or financial situation with regard to DMT choice. However, many rely on assistance for DMT coverage or are not able to take a DMT as directed or at all due to their current insurance or financial situation.

Supported by: CMSC and the Foundation of the CSMC, NARCOMS

Disclosure: Stacey S. Cofield: MedImmune, American Shoulder Elbow Society (consulting fees). Tuula Tyry, Sandre McNeal, Guoqiao Wang: Nothing to dis-close. Amber R. Salter: GlaxoSmithKline (DSMB service). Robert J. Fox: Actelion, Biogen Idec, Novartis (advisory committees, fees for non-CME services from com-mercial interests or their agents); Actelion, Biogen Idec, MedDay, Novartis, Quest-cor, Teva, XenoPort (consulting fees); Novartis (grant/research support). Ruth Ann Marrie: CIHR, PHAC, MHRC, HSC Foundation, MS Society of Canada, MS Scientific Foundation, CMSC Foundation, Rx & D Health Research Foundation, Bayer Inc, Sanofi-Aventis, EMD Serono (grant/research support). Gary Cutter: Antisense Therapeutics Limited, Sanofi-Aventis, Bayhill Pharmaceuticals, Bayer Pharmaceuticals, BioMS Pharmaceuticals, Daichi-Sankyo, GlaxoSmithKline Pharmaceuticals, Genmab Biopharmaceuticals, Medivation, Peptimmune, PTC Therapeutics, Teva, Vivus, National Heart, Lung, and Blood Institute, National Institute of Neurological Disorders and Stroke, National Multiple Sclerosis Society (DSMB service); EMD Serono, EDJ Associates, Aegis Creative Marketing, Eli Lilly, UT Southwestern University, Klein Buendel, University of Illinois Health Policy Center, Somnus Therapeutics, Klein-Buendel Incorporated, Enzo Pharma-ceuticals, Somnus Pharmaceuticals, Teva, Biogen Idec, Advanced Health Media, PTC Therapeutics, Vivus, National Heart, Lung, and Blood Institute, National Institute of Neurological Disorders and Stroke, National Multiple Sclerosis Soci-ety, Alexion, Accentia, Barofold, CibaVision, Novartis, Consortium of Multiple Sclerosis Centers (consulting fees).

Keywords: Disease-modifying treatments in MS, Economic issues and MS, Health insurance

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Individuals with MS need access to resources to function safely and independently with a relatively high quality of life (Osborne et al., 2013). Many such resources are available; however, individuals and families may not know how to find them. The Society addresses these concerns through a nationwide MS Navigator program that starts at the Information Resource Center (IRC), a 5 day/week call cen-ter, connecting people affected by MS to the information, resources, and support needed to move their lives forward. Objectives: Not applicable. Methods: The current study evaluated the MS Naviga-tor program at immediate post call and 6-week follow-up. The base-line sample contains 294 participants (91% people with MS) with a mean age of 48.22 years and mean length of diagnosis of 13.01 years); the 6-week sample contains 193 participants (people with MS). All participants spoke with an MS Navigator who listened to them and addressed their particular needs. Data were collected via retrospective pre/post and 6-week follow-up surveys. Results: Paired-sample t tests found that people with MS with higher levels of MS symptoms reported a significant increase in Mental Health Quality of Life (SF-12) (t49 = 3.42, P < .01) from post (mean 40.10, SD 11.81) to 6 weeks (mean 42.60, SD 11.83); decreases in stress (MSQOL) (t100 = 1.28, P < .01) from post (mean 3.45, SD 1.14) to 6 weeks (mean 3.19, SD 1.12); increase in confidence in one’s ability to cope (Liverpool self-efficacy scale; P < .01); and increase in health-care satisfaction (P < .01). Immediate post outcomes include decreased anxiety and stress and increased knowledge and support (people with MS and SP). Conclusions: Through a nationwide team approach and technology, the IRC provides an evidence-based ser-vice to improve lives for people affected by MS. Having the proper resources to manage MS, both medically and psychosocially, can dramatically improve one’s quality of life (WHO, 2006). The MS Navigator program is a successful first step in connecting individuals affected by MS to the resources that they need to live their best lives.

Disclosure: Nothing to discloseKeywords: Economic issues and MS, MS and the caregiver/family, Resources and support for people living with MS

(QL04) PHYSICIAN RATING OF FITNESS-TO-DRIVE IN MULTIPLE SCLEROSISHannes Devos,1 Abiodun E. Akinwuntan,2 Maud Ranchet,1 Mark Tant3

1Physical Therapy, Georgia Regents University, Augusta, GA; 2Administration, Georgia Regents University, Augusta, GA; 3CARA, Belgian Road Safety Institute, Brussels, Belgium

Background: In Belgium, individuals with multiple sclerosis (MS) are typically referred by their physician for an official fitness-to-drive assessment. The referrals usually include the physician’s judgment of the patient’s fitness-to-drive. At the assessment center, a standardized on-road assessment is administered as part of a comprehensive fit-ness-to-drive evaluation. The on-road assessor also makes a judgment of the patient’s fitness-to-drive after the test. Objectives: To deter-mine the reliability between the physician’s judgment and that of the on-road assessor. Methods: Referring physicians and on-road asses-sors used the same three-class decision as outcome variable: 1) favor-able, ie, no substantial problems with on-road driving; 2) reserved, ie, some concerns with on-road driving; and 3) unfavorable, ie, serious concerns with on-road driving. The percentage agreement (po), weighted kappa (kw), and prevalence and bias adjusted kappa (PABAK) between the physician’s and assessor’s judgment were determined using the data of 95 random individuals (mean ± SD age = 53 ± 12 years; 50 [55%] females). The referring physician was either a neurologist or a general practitioner. Results: The on-road assessor found no concerns on the road test in the majority of MS drivers (n = 87 [92%]). Six (6%) exhibited difficulties on the road that were of concern, and two (2%) were advised to discontinue driving based on the findings of the road test. The po between referring physi-cians and on-road assessors was 83%, and the kw was 0.11 (P = .21). The low kw was likely the result of the uneven proportion in the three categories. The PABAK adjusted for the uneven distribution and showed a reliability coefficient of 0.76 (P < .0001). No differences

with relapsing forms of multiple sclerosis (RMS). It has a well-characterized safety profile. The ongoing, global phase 4 Teri-PRO study (NCT01895335) is examining efficacy and tolerability of, and satisfaction with, teriflunomide in routine clinical practice using patient-reported outcomes (PROs) in patients with RMS. Objectives: To describe demographics and baseline disease characteristics of patients enrolled in Teri-PRO in the United States and rest of the world (ROW). Methods: Teri-PRO is a prospective, single-arm, open-label study in 1001 patients with RMS receiving once-daily teriflunomide 14 mg or 7 mg for 48 weeks, with doses given according to local labeling in Europe, North America, and Latin America. Primary out-come is global satisfaction, measured by scores on the Treatment Sat-isfaction Questionnaire for Medication (version 1.4) assessed at 48 weeks (or end of treatment). Secondary outcomes include other PRO metrics over the study period, relapse and disability assessment, and safety. Results: Enrollment within the United States is complete: 609 patients were screened, and 545 included in the study; 472 (86.8%) and 72 (13.2%) received teriflunomide 14 mg and 7 mg, respec-tively. Mean (SD) age was 50.7 (10.5) years; 76.1% were female. Mean (SD) time since first symptom was 14.7 (9.7) years, baseline mean (SD) Expanded Disability Status Scale (EDSS) score was 3.74 (1.95), and 70.8% reported use of ≥1 disease-modifying therapy (DMT) in the last 2 years. As of November 14, 2014 (recruitment ongoing), 391 ROW patients (Canada, Europe, and Latin America) had been screened, 369 were included in the study, and 334 had begun receiving teriflunomide 14 mg. Mean (SD) age was 42.6 (10.0) years; 72.5% of patients were female. Mean (SD) time since first symptom was 11.2 (8.7) years, baseline mean (SD) EDSS score was 2.29 (1.57), and 70.7% reported use of ≥1 DMT in the last 2 years. Enrollment was completed on December 5, 2014. Data on all included patients (N = 1001) will be presented in the poster. Con-clusions: Teri-PRO will provide valuable information on the use of teriflunomide in routine clinical practice, including patient treatment satisfaction, safety, and efficacy. Comparison of baseline character-istics indicate some differences between US patients and those from other regions, which may reflect differences in prescribing practices and overall disease management.

Supported by: Genzyme, a Sanofi companyDisclosure: Patricia K. Coyle: AbbVie, Acorda, Accordant, Bayer, Biogen Idec, Genentech, Genzyme, Mylan, Novartis, Roche, Serono, Teva, Genzyme/Sanofi, Genentech/Roche (consulting fees); Actelion, Novartis, Opexa (grant/research sup-port). Christopher LaGanke: Acorda, Bayer, Biogen Idec, EMD Serono, Novartis, Pfizer, Questcor, Sanofi/Genzyme, Teva Neurosciences, UCB (fees for non-CME services from commercial interests or their agents); Acorda, Bayer, Biogen Idec, EMD Serono, Novartis, Pfizer, Questcor, Sanofi/Genzyme, Teva Neurosciences, UCB (speakers’ bureau); Acorda, Bayer, Biogen Idec, EMD Serono, Novartis, Pfizer, Questcor, Sanofi/Genzyme, Teva Neurosciences, UCB (consulting fees); Biogen Idec, Novartis, Sanofi/Genzyme, Teva Neurosciences, Vaccinex (grant/research support). Bhupendra Khatri: Bayer, Biogen Idec, Genzyme, Novartis, Pfizer, Questcor, Serono, Terumo, Teva (consulting fees, grant/research support). Ralf Gold: Biogen, Teva, Bayer Schering, Elan, Genzyme, Roche (consulting fees); Genzyme, Teva, Biogen, Bayer Schering, Merck Serono (grant/research support). Steven Cavalier: Genzyme, a Sanofi company (salary), Sanofi (ownership inter-est). Francesca Baldinetti: Genzyme, a Sanofi company (salary). Sandrine Brette: Lincoln, mandated by Sanofi (salary). Keith R. Edwards: Actelion, Biogen Idec, Eisai, Eli Lilly, Genentech, Genzyme, Novartis, TauRx Therapeutics, Vaccinex (grant/research support); Biogen Idec, Genzyme, Novartis Pharmaceutical (speak-ers’ bureau, consulting fees).Keywords: Disease-modifying treatments in MS

(QL03) IMPACTING LIVES AFFECTED BY MULTIPLE SCLEROSIS: EVALUATION OF THE NATIONAL MULTIPLE SCLEROSIS SOCIETY’S MS NAVIGATOR PROGRAMLisa Custy

Advocacy, Services and Research, National Multiple Sclerosis Society, Denver, CO

Background: Part of the fundamental mission of the National Mul-tiple Sclerosis Society is to help individuals affected by MS overcome the challenges associated with this chronic and debilitating disease.

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Background: A grant was awarded to the Tanner Foundation from Acorda Therapeutics for “Tanner Center Health Miles” in April 2013. The funds provided were used to cover purchase of pedometers from Virgin Health Miles, a monthly participation fee for web-based moni-toring, and bimonthly walking sessions to provide supervised exer-cise with an educational component. Objectives: The program was designed to meet two goals. One goal was to promote healthy life-style through exercise to gain cardiovascular benefits, increase endur-ance, decrease rate of depression, increase flexibilty, and manage weight. The second goal addressed by the program was to increase knowledge of multiple sclerosis (MS) in the areas of symptom man-agement, exercise protocols, community resources, and updates on medication and research. Methods: Participants enrolled in Tanner Center Health Miles were required to complete the following metrics: Tanner Center Health Miles Exercise Questionnaire, Multiple Sclerosis Quality of Life–54 (MSQOL-54), Fatigue Severity Scale (FSS), Timed Up and Go (TUG) test, and Timed 25-Foot Walk (T25FW) test. All metrics were completed at initiation of the program, at 6 months, and at program conclusion. 24 walking sessions were offered with vary-ing topics of discussion. Pedometers were issued to each participant through Virgin Health Miles, and walking steps/activity miles were monitored on a monthly basis. The levels were as follows: Level 1 represents less than 7000 steps per day; Level 2, 7000–11,999 steps/15–29 active minutes; Level 3, 12,000–19,999 steps/30–44 active minutes; Level 4, 20,000+ steps/45+ active minutes. Incen-tives were given at 3 months, 6 months, and at the close of the program. Results: Initial data on 39 participants were collected, 6-month follow-up data were obtained for 11 participants, and 11 completed the final metrics. The FSS score for 7 of the 11 partici-pants decreased from before to after the walking program. The score remained the same for 2 participants and increased only slightly (by 1 point) in 2 participants. The MSQOL-54 scores improved for all participants except one from program initiation to close. The Tanner Center Health Miles Exercise Questionnaire captured 3 participants reporting not exercising at initial evaluation but exercising at pro-gram close. The remaining 8 were exercising prior to the program and continued to exercise at program close. Of the two walking met-rics, the TUG scores for participants improved within the 12-month program for 7 of the 11 participants. One participant cut the TUG time by 7 seconds. Improvements on the T25FW occurred for 6 of the 11 participants. There were 2 participants who reached Level 2 in the pedometer program within 4 months and remained at this level for the duration of the program. One participant who achieved this level and remained at this level attended 19 of the 24 walking sessions. Conclusions: Results of this program suggest that exercise with accountability through bimonthly meetings and daily monitoring through a pedometer can lead to increased activity and improve-ments in the areas of mobility and quality of life in people with MS.

Supported by: Acorda TherapeuticsDisclosure: Tracy Flemming Tracy: Acorda Therapeutics (grant/research sup-port). Virgina R. Weinacker, Emily S. Riser: Nothing to disclose. Bess Martin: Acorda Therapeutics (speakers’ bureau).Keywords: Comprehensive care and MS, Management of activities of daily living in MS, MS and the caregiver/family

(QL07) ASSOCIATION BETWEEN MEASURES OF DISABILITY AND EMPLOYMENT IN SECONDARY PROGRESSIVE MULTIPLE SCLEROSIS: BASELINE DATA FROM THE ASCEND NATALIZUMAB TRIALMyla D. Goldman,1 Diego Cadavid,2 Carmen Castrillo,2 Yun Chen,2 Qunming Dong,2 Crystal Watson,2 Deb Steiner,2 Daniel Mikol,2 Aaron E. Miller3

1University of Virginia, Charlottesville, VA; 2Biogen Idec, Cambridge, MA; 3Icahn School of Medicine at Mount Sinai, The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, New York, NY

Background: Disability in multiple sclerosis (MS) has been shown to affect multiple aspects of patients’ lives, including employment status. ASCEND is an ongoing international, phase 3b, random-ized, double-blind, placebo-controlled study to evaluate whether

were found in po between neurologists (83%) and general practitio-ners (88%, Fisher exact = 0.56). Conclusions: In this sample of drivers with MS, physicians were usually accurate in their appraisal of their patients’ driving capabilities.

Supported by: National Multiple Sclerosis SocietyDisclosure: Nothing to discloseKeywords: Comprehensive care and MS, Management of activities of daily living in MS

(QL05) HAIR PHOTOGRAPHY PROJECT: EXPLORING THE CLINICAL COURSE OF HAIR THINNING ASSOCIATED WITH TERIFLUNOMIDEKeith R. Edwards,1 Lori Hendin Travis,2 Annette Okai,3 Scott Jackson,4 Lisa Farnett,5 Steven Cavalier,5 Darren Stam,5 Ken Liu5

1Multiple Sclerosis Center of Northeastern New York, Latham, NY; 2Phoenix Neurological Associates Ltd, Phoenix, AZ; 3Multiple Sclerosis Treatment Center of Dallas, Dallas, TX; 4Baton Rouge Clinic, Baton Rouge, LA; 5Genzyme, a Sanofi company, Cambridge, MA

Background: Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting multiple sclerosis (MS). In the phase 3 TEMSO (NCT00134563) and TOWER (NCT00751881) trials, ~13% of patients receiving teriflunomide 14 mg experienced hair thinning compared with ~4% receiving placebo. Hair thinning gen-erally occurred in the first 6 months and resolved without corrective treatment while on teriflunomide (median duration 135 days). Most cases were mild to moderate, and only 6% of teriflunomide patients who reported hair thinning discontinued treatment. Photographs of patients with self-reported hair thinning in a real-world setting could help health-care professionals (HCPs) and patients set expectations before starting teriflunomide. Objectives: To illustrate the clini-cal course of hair thinning in patients who experience this adverse event (AE) during treatment with teriflunomide. Methods: Patients who reported hair thinning to HCPs during teriflunomide treatment were eligible. At onset and resolution, HCPs completed hair thinning questionnaires, ranking patient-perceived severity from 0 to 10. With a standardized protocol and camera, patients were photographed from five standard views (anterior, posterior, left lateral, right lateral, anterior superior) and an optional manipulated view with hair pulled back. Results: Of the 31 patients who completed follow-up visits, most were female (30/31) and white (28/31), and had no prior history of hair loss (28/31). Average patient age was 51.0 years, and mean time to onset of hair thinning was 81 days. Most cases were classified as mild (19/31, 61%), and the rest were moderate (12/31, 39%), with a mean patient severity perception of 4.9/10. On average, follow-up visits took place 268 days (~9 months) after onset of hair thinning. Complete/near-complete resolution or marked improvement was reported in 26/31 patients at follow-up. Four patients discontinued teriflunomide: three for other reasons and one for AEs including hair thinning. Photographs of patients at onset and follow-up will be presented. Conclusions: Hair thinning in these patients was consistent with observations from the clinical trial pro-gram: cases were usually mild, and most patients recovered fully. As with any potential AE, it is important to ensure appropriate expecta-tions through patient education in advance of treatment.

Supported by: Genzyme, a Sanofi companyDisclosure: Keith R. Edwards: Actelion, Biogen Idec, Eisai, Eli Lilly, Genentech, Genzyme, Novartis, TauRx Therapeutics, Vaccinex (grant/research support); Biogen Idec, Genzyme, Novartis (consulting fees). Lori Hendin Travis: Acorda, Biogen Idec, EMD Serono, Genzyme, Novartis, Questor (consulting fees). Annette Okai: Bayer Pharmaceuticals, Biogen Idec, EMD Serono, Genzyme, Teva Neu-roscience, Questcor (consulting fees); Genzyme, Novartis, SunPharma (grant/research support). Scott Jackson: Nothing to disclose. Lisa Farnett, Steven Cava-lier, Darren Stam, Ken Liu: Genzyme, a Sanofi company (salary).Keywords: Disease-modifying treatments in MS

(QL06) TANNER HEALTH MILES: WALKING AND TALKING MULTIPLE SCLEROSISTracy Flemming Tracy, Virgina R. Weinacker, Emily S. Riser, Bess Martin

Rehabilitation, Tanner Center for MS, Birmingham, AL

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cant difference between the two groups on the overall score. Overall, individuals with MS reported more problems managing money than healthy controls. Participants with MS had more problems using ATM machines, and reported having more debts. However, healthy controls reported more problems paying their bills on time compared with individuals with MS. Prospective memory and executive func-tion were significantly correlated with money management. Finally, the results revealed that the self-report of functional status (Functional Behavior Profile) was significantly correlated with self-reported money management skills. Conclusions: To our knowledge, this is the first study to examine money management in MS. Money management is an important IADL that could present problems for individuals with MS. Future research should continue to explore this topic to better understand the nature of the problem.

Supported by: BiogenDisclosure: Nothing to discloseKeywords: Economic issues and MS, Employment in MS, Management of activi-ties of daily living in MS

(QL09) TO WHAT EXTENT DOES JC VIRUS STATUS INFLUENCE PATIENT DECISIONS REGARDING TREATMENT WITH NATALIZUMAB?William Lusher, Nina Jennings, Karen Vernon, David Rog, Paul Talbot

Neurosciences, Salford Royal NHS Trust, Salford, United Kingdom

Background: The stratify JC virus (JCV) test started to be used at Salford Royal NHS Trust, a major tertiary neurology center in the United Kingdom, for patients receiving or being considered for treat-ment with natalizumab. The JCV test is not mandatory at this time for patients before starting or being on treatment at this center, as it was felt that a positive test might deter patients from treatment, because of the risk of developing progressive multifocal leukoencephalopathy increasing from 1 in 10,000 if JCV negative, to 1 in 1429 if JCV positive in the first 2 years of treatment, to 1 in 189 at 2 to 4 years. It was decided to audit the results of these tests to see if a positive test affects how patients perceive the risk of treatment. Objectives: To determine to what extent JC virus status influences patients’ decisions regarding treatment with natalizumab. Methods: Retrospective case note analysis of these patients was undertaken to determine whether a decision to remain on or start treatment was affected by a positive test result. All patients who underwent JCV testing from the start of its use at the center in August 2011 to the end of June 2014 were included in the audit (n = 150). Demographics of the patient cohort were an average age of 37.9 years (range 18–63), 68.7% female (n = 105), and 54% (n = 82) being DMT-naïve. As of 9/25/14, 190 patients were being treated with natalizumab. Results: Of the patients tested, 55 were treated with natalizumab and 95 were tested before deciding whether or not to begin treatment. Of the 150 tests performed at this center, all patients treated with natalizumab (n = 55) remained on treatment regardless of JCV status (positive n = 21, negative n = 34); additionally, one patient who seroconverted from negative to positive elected to remain on treatment. In patients tested prior to treatment, JCV positivity (n = 45) resulted in 9 elect-ing not to start treatment, and JCV negativity (n = 50) resulted in 6 electing not to start natalizumab. Conclusions: JCV positivity before treatment reduced the likelihood that a patient would elect to be treated with natalizumab by 11% (12% JCV-negative vs. 23% JCV-positive).

Supported by: NoneDisclosure: William Lusher, Nina Jennings: Biogen Idec (fees for non-CME services from commercial interests or their agents). Karen Vernon: Biogen Idec, Genzyme, Teva, Bayer Schering, Novartis, Merck Serono (consulting fees); Biogen Idec, Novartis, Teva (fees for non-CME services from commercial interests or their agents). David Rog: Biogen Idec, Genzyme, Teva, Bayer Schering, Novartis, Merck Serono (consulting fees, fees for non-CME services from commercial interests or their agents). Paul Talbot: Novartis, Biogen Idec, Teva (fees for non-CME ser-vices from commercial interests or their agents).Keywords: Comprehensive care and MS, Disease-modifying treatments in MS, Natalizumab

natalizumab reduces disability progression unrelated to relapses in patients with secondary progressive MS (SPMS). Objectives: To investigate differences in clinical or patient-reported outcomes by employment status in SPMS patients randomized into the ASCEND trial. Methods: Subjects with SPMS were randomized 1:1 to treatment with natalizumab or placebo for 2 years. At enrollment, detailed information on employment was obtained from all subjects. Neurologic assessments include measures of walking ability (T25FW, MSWS-12, 6MWT), hand dexterity (ABILHAND, 9HPT), physical disability (EDSS), and cognitive impairment (SDMT for all subjects and a novel composite endpoint based on SDMT, SRT, BVMTR, and PASAT for a subgroup of participants). Associations between employment status (full-time/part-time or unemployed) and baseline disability outcome measures were evaluated using pooled blinded subject data and stratified by standard demographic variables (age, gender, level of education) and employment. Results: At baseline, 339 of the 889 (38%) SPMS patients enrolled in ASCEND were employed (29% outside the home, 3% at home, 6% homemakers, <0.5% students) while 550 (62%) were unemployed. At baseline, unemployed subjects had significantly longer T25FW times, worse MSWS-12 scores, and worse EDSS scores than employed subjects (all P < .0001). Employed subjects at baseline had better 6MWT distance, better ABILHAND, 9HPT, and SDMT scores, and, in the cognitive impairment composite endpoint subgroup, better composite cognition endpoint z score than unemployed subjects. There was no significant difference in age between unemployed (mean 47.5 years) and employed (mean 46.7 years) subjects. A significantly higher percentage of employed subjects were married (70.1% vs. 60.7% unemployed) and had more years of education (mean 13.8 vs. 12.9 years unemployed). Conclusions: Strong associations were found at baseline between unemployment and worse physical and cogni-tive disability outcomes in the ASCEND study.

Supported by: Biogen IdecDisclosure: Myla D. Goldman: Concert Pharmaceuticals (consulting fees); Novartis, Biogen (grant/research support). Diego Cadavid, Carmen Castrillo, Yun Chen, Qunming Dong, Crystal Watson, Deb Steiner, Daniel Mikol: Biogen Idec (salary). Aaron E. Miller: Acorda, Biogen Idec, EMD Serono, Genzyme/Sanofi, GlaxoSmithKline, Novartis, Nuron Biotech, Questcor, Roche, Teva (consulting fees); Acorda, Biogen Idec, Genentech, Genzyme, Genzyme/Sanofi, Novartis, Questcor, Roche (grant/research support).Keywords: Employment in MS, Natalizumab

(QL08) THE EFFECTS OF MULTIPLE SCLEROSIS ON DAILY MONEY MANAGEMENT ACTIVITIESShannon L. Haas,1 John DeLuca,1,2 Yael Goverover1,3

1Neuropsychology and Neuroscience, Kessler Foundation, West Orange, NJ; 2Department of Physical Medicine and Rehabilitation and of Neurology and Neurosciences, Rutgers New Jersey Medical School, Newark, NJ; 3Occupational Therapy, New York Univeristy, New York, NY

Background: Managing one’s own finances is an instrumental activity of daily living (IADL) crucial to independent functioning. Money management requires executive-attentional abilities such as planning, prioritizing, and monitoring, as well as retrospective and prospective memory. Multiple sclerosis (MS) may result in cognitive impairment including executive functioning, memory, and processing speed. Therefore, it is important to understand how people with MS manage their finances, and whether it should be addressed in reha-bilitation. Objectives: This study includes three research questions: 1) Do MS patients report more problems in managing finances than healthy controls? 2) Are executive functioning and memory impair-ments associated with money management? 3) Are money manage-ment skills associated with self-report of functional status? Methods: Participants included 30 individuals with MS and 18 healthy con-trols. Participants were administered a battery of neuropsychological tests as well as a money management survey. The money manage-ment survey required participants to provide basic responses (ie, “Never,” “Sometimes,” or “Often”) to 13 questions about their daily money management activities. Results: Results approached a signifi-

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to a dearth of proactive programs, the National Multiple Sclerosis Society developed “Everyday Matters: Living Your Best Life with MS.” Objectives: To empower people living with MS to live their lives through the use of positive psychology. Methods: Over the course of five sessions, the program aims to increase participants’ knowledge of positive psychology and how to apply these tenets to the everyday challenges of living with MS. Results: Current data are from pre (254), post (209), and 3-month follow-up surveys (164), with 12-month surveys being actively collected. The baseline sample shows a majority of people with MS (80%), 34% having a diagnosis duration of <5 years, 70% having a diagnosis of relapsing-remitting MS, and 41% reporting sometimes experiencing depression. Paired-sample t tests run on pre and 3-month responses showed significant increases in Satisfaction with Life Scale (SWLS; people with MS [t119 = 5.04, P < .05] and CP); confidence in MS symptom management (MSSE; t112 = 2.30, P < .05); positive/optimistic outlook (people with MS [t126 = 5.91, P < .05] and CP). Additional findings include use of positive psychology, MS-related resources, and an action plan. Conclusions: “Everyday Matters” is one of the few MS-specific programs being offered using the principles of positive psychology to assist in addressing life challenges. Results demonstrate evidence of program success in multiple outcomes. Specifically, improved satisfac-tion with life at 3 months is encouraging, as this construct has been correlated to mental health and may lead to improved quality of life (Pavot & Diener, 2008). Additional implications of increasing posi-tive constructs are better medication adherence, less morbidity, and increased longevity (Cuffee et al., 2012). The Society has created an effective positive psychological intervention for the MS population, improving both MS-specific and general positive constructs.

Supported by: Genzyme, a Sanofi CompanyDisclosure: Nothing to discloseKeywords: Management of activities of daily living in MS, MS and the care-giver/family, Positive psychology

(QL12) WITHDRAWN

(QL13) BALLROOM DANCE FOR PEOPLE WITH MULTIPLE SCLEROSIS: PRELIMINARY EFFICACYAlexander V. Ng,1 Sheri L. Bunyan,2 Jimin Suh,1 Tyler J. Gregory,1 Shannon Gambon,1 Lauren Kalita1

1Physical Therapy/Exercise Science, Marquette University, Milwaukee, WI; 2Physical Therapy, Concordia University, Mequon, WI

Background: Ballroom or social dance is a physical activity in which people move to music with a partner. Ballroom dance may be an effective exercise mode for people with multiple sclerosis (MS) who have mild to moderate impairments, in part because a dance partner can provide external support. There is also a cogni-tive demand in learning and remembering new movements. Until recently, ballroom dance had not been investigated in people with MS. We have shown previously that ballroom dance can provide a mild to moderate exercise intensity. Objectives: The purpose of this ongoing study was to investigate the efficacy of an 8-week recreational ballroom dance program in people with MS in terms of physical function and other quality of life (QOL)–related outcomes. Methods: To date, 12 people with MS (11 female, mean [SD] age 47 [10] years) participated who were ambulatory with minimal to moderate aid and able to physically take part in the program. A nondance control group consisted of 7 people with MS (7 female, mean [SD] age 46 [9] years). The intervention comprised 8 to 10 weeks of 1-hour sessions, twice a week, and included rumba, foxtrot, waltz, swing, American tango, push-pull, and salsa. Participants were paired with a partner without MS. Pre-post measures included QOL (PROMIS Global Short Form), Beck Depression Inventory (BDI), Fatigue Impact Scale (FIS), 6-Minute Walk (6MW), Berg Balance Scale, Timed Up and Go (TUG), Dynamic Gait Index (DGI), Timed 25-Foot Walk (T25FW), 3-second Paced Auditory Serial Addition

(QL10) THE IMPACT OF RELAPSE ON PRODUCTIVITY, COSTS, AND RESOURCE UTILIZATION IN MULTIPLE SCLEROSIS: A RETROSPECTIVE US DATABASE ANALYSISJohn J. Ko,1 Juzer Lotya,2 Caitriona O’Neill,2 Tara A. Nazareth,3 Rahul Sasane3

1The University of Texas at Austin, Austin, TX; 2Novartis Dublin Business Solution Centre, Global Business Services, Dublin, Ireland; 3US Health Economics and Outcomes Research, Novartis Pharmaceuticals Corporation, East Hanover, NJ

Background: Multiple sclerosis (MS) relapses are unpredictable, debilitating, and costly. Objectives: To assess the impact of relapse on productivity, health-care resource utilization (HCRU), and costs in MS patients over a 4-year period in the United States. Methods: A retrospective study of Truven Health MarketScan claims database and Health and Productivity Management database (HPM) during 2006–2012 was conducted. Adult MS patients (≥2 MS diagnoses ≤60 days, ICD-9-CM: 340.xx) with continuous medical and pharma-cy benefits in the 1-year baseline period and 4-year follow-up period were included (no single gap in enrollment >40 days). A published claims-based algorithm was employed to categorize patients into two groups based on care-seeking behavior: no relapse or relapse. Descriptive statistics were generated on baseline demographics and clinical characteristics. Annual MS-related HCRU (number of hospital-izations, ER visits, and physician office visits), productivity (number of days absent), and associated costs ($) were estimated during the follow-up period. Results: A total of 4119 MS patients had medical and pharmacy claims, of whom 411 also had HPM data; 77% were female, 65% were employed full time, and 67% were covered by a PPO. In the relapse and no relapse groups, the mean (SD) number of annual MS-related claims for hospital admissions, ER visits, and physician office visits were 1.5 (1.8) and 0 (0), 2.6 (4.4) and 1.7 (1.9), and 13.8 (9.2) and 7.8 (6.8), respectively. Mean annual MS-related costs were $23,347 ($103,303) and $0 ($0), $2714 ($30,817) and $714 ($1531), and $1661 ($1818) and $899 ($1024), respectively. In terms of productivity, for the relapse and no relapse groups, the mean number of days absent from work per year were 18.9 (25.6) and 13.6 (13.8), respectively. Over the follow-up period, the mean number of days absent per year increased from 17 to 50 days (per 1000 patients) in the relapse group and decreased from 30 to 21 days (per 1000 patients) in the no relapse group. Conclusions: Our study describes annual impacts on productivity, HCRU, and cost in MS patients with confirmed relapse versus those without. In this relatively healthy, commercially insured population, MS relapses are associated with increased economic and human burden. This study may underestimate the full burden of MS by not capturing outcomes such as non-clinically confirmed relapses, which are not reflected in claims data.

Supported by: Novartis PharmaceuticalsDisclosure: John J. Ko: Nothing to disclose. Juzer Lotya, Caitriona ONeill, Tara A. Nazareth, Rahul Sasane: Novartis Pharmaceuticals (salary, ownership interest).Keywords: Productivity, costs, and resource utilization in multiple sclerosis

(QL11) LIVING YOUR BEST LIFE WITH MS? EXAMINATION OF THE NATIONAL MULTIPLE SCLEROSIS SOCIETY’S EVERYDAY MATTERS PROGRAMKimberly Koch,1 Sara Anne Tompkins2

1Advocacy, Services and Research, National Multiple Sclerosis Society, Denver, CO; 2Program Planning and Evaluation Consulting, Madipen, LLC, Fort Collins, CO

Background: Everyone has their own idea of their “best life.” For people living with multiple sclerosis (MS), the idea of that “best life” can change owing to the challenges of having a chronic and unpredictable disease. As MS can have significant implications for mental and physical functioning, interventions teaching positive and empowering strategies are needed. Interventions aimed at cul-tivating positive feelings, behaviors, and emotions have resulted in significant enhancement in well-being and decreases in depressive symptoms. In the MS population, such interventions may lead to improved ability to face disease-specific life challenges. In response

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(QL15) MULTIPLE SCLEROSIS IN US MINORITIES: RESULTS OF A RESEARCH STUDY DESIGNED TO UNDERSTAND EDUCATIONAL NEEDS OF HISPANIC AND AFRICAN AMERICAN PATIENTS WITH MSGregory D. Salinas,1 Brandon Coleman,1 Eleana Hardy,2 Leslie Meltzer2

1CE Outcomes, LLC, Birmingham, AL; 2Biogen Idec, Cambridge, MA

Background: Identifying multiple sclerosis (MS) patient needs is a critical component to developing the appropriate tools for identifying barriers to treatment and designing successful education interven-tions. An abundance of literature assesses the impact of MS on quality of life, and a moderate range of material regarding patient needs exists, with increased attention paid to this area in the last few years. However, most literature in these areas focuses primarily on the general population, with limited attention to minorities, specifi-cally African Americans and Hispanics. Objectives: This study was conducted to understand needs specific to minority patients in order to develop targeted educational opportunities for this population. Methods: A survey was developed to understand varying com-ponents of patient educational need, including experience with MS diagnosis, satisfaction with quality of medical care, attitudes regard-ing clinical trials, barriers to medical care, preferred MS educational sources and topics, and unmet MS educational needs. Screening questions were designed to ensure that the survey would be directed to US minorities, specifically African American and Hispanic patients, and were available in both English and Spanish. Data are being collected using an online survey system and analyzed using descrip-tive and inferential statistics. Survey items, including socioeconomic demographics, years with MS, and current treatment regimen, will be used to stratify the responses and help understand specific needs of this community. Results: Data are expected to be collected from 250 patients, with a minimum of 50 in each minority group; the study is currently ongoing. Conclusions: Presented results will show MS-specific educational needs identified by minority patients, com-parisons with published needs of the MS community at large, and recommendations for educational and informational channels to best address these needs.

Supported by: Biogen IdecDisclosure: Gregory D. Salinas, Brandon Coleman: Nothing to disclose. Eleana Hardy, Leslie Meltzer: Biogen Idec (salary).Keywords: Economic issues and MS, Management of activities of daily living in MS

(QL16) ICONQUERMS: A PATIENT-POWERED RESEARCH NETWORK FOR MULTIPLE SCLEROSISHollie Schmidt,1 Robert N. McBurney,1 Sara Loud,1 Revere P. Kinkel2

1Accelerated Cure for MS, Waltham, MA; 2University of California San Diego, La Jolla, CA

Background: Accelerated Cure for MS (AC-MS) is an advo-cacy organization that creates resources that catalyze collaborative research. In partnership with Arizona State University and Feinstein Kean Healthcare, AC-MS has developed an MS Patient-Powered Research Network (MS-PPRN), called iConquerMS, to drive and enable research on topics important to people with multiple sclerosis (MS). iConquerMS is a member of PCORnet, a linked group of PCO-RI-funded research networks incorporating health data from millions of people across the United States. Objectives: 1) Facilitate patient enrollment in the network, with a goal of 20,000 members enrolled by September 2015. 2) Collect de-identified patient-reported data, biosamples, and electronic health records (EHRs) from participants to support research studies. 3) Provide mechanisms for investigators and patients alike to propose topics for research studies. 4) Facilitate the review, approval, and implementation of research studies using samples and data collected from network participants. 5) Dissemi-nate information such as network population data and research find-ings to network members. Methods: Participants enroll and provide informed consent via the web portal iConquerMS.org. Enrolled par-ticipants provide health data by completing surveys and uploading

Test (PASAT-3), and 9-Hole Peg Test (9HP). Heart rate variability (HRV) was analyzed from a 10-minute rest EKG. Analyses were by paired t tests and Wilcoxon signed rank tests. Values are mean (SD). Results: Results from the dance group are reported. Improvements in physical function were noted for 6MW (pre = 456 [124] m, post = 492 [126]; P = .002), TUG (pre = 10.4 [3.8] s, post = 8.9 [4.4]; P = .003). T25FW tended to improve (pre = 6.1 [2.5] s, post = 5.8 [2.6]; P = .08). DGI improved (pre =19 [7], post = 21 [5]; P = .04), though Berg Balance Scale did not (P = .26). The 9HP improved (pre = 23 [2] s, post = 21[2]; P = .04), as did PASAT-3 (pre = 43 [13], post = 48 [11]; P = .05). Improvements in 9HP were driven by changes in the nondominant hand. FIS tended to improve (pre = 42 [36], post = 26 [24]; P = .08). No other significant differences or trends were noted. Conclusions: Our preliminary results indicate that ballroom dance can be a fun social form of physical activity for people with MS that can result in improved motor performance, gait, endurance, and cognition. Fatigue may be lessened independent of changes in cardiac autonomic balance (ie, HRV).

Supported by: Greater Milwaukee FoundationDisclosure: Nothing to discloseKeywords: Complementary/alternative therapies in MS, Exercise

(QL14) A COMPREHENSIVE REVISION OF THE INCAPACITY STATUS SCALE: ISS-2Jeffrey G. Portnoy,1 Marnina B. Stimmel,1 Sara Flood,1 Gabriel Hoffnung,1 Mary Ann Picone,2 Lisa Glukhovsky,1 Jessica H. Sloan,1 Roseann Archetti,1 Eliana Pasternak,1 Jason Botvinick,1 Elana Mendelowitz,1 Frederick W. Foley1,2

1Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY; 2Holy Name Medical Center, Teaneck, NJ

Background: The Incapacity Status Scale (ISS), part of the Minimal Record of Disability (MRD) for Multiple Sclerosis (MS), was one of the first measures of disability designed for the MS population. While the scale is psychometrically sound, it has not seen as much use in recent research as Kurtzke’s Expanded Disability Status Scale (EDSS). As a patient-reported outcome (PRO) rather than a practitioner-evaluated scale of function, the ISS-2 has the potential to streamline evaluation in clinical settings; it can be completed by a patient or caregiver, either ahead of a patient’s visit or in the waiting room. The ISS-2 can also be used as a structured clinical interview tool that can provide a more precise description of patient functioning than a numerical rating on a systems-based scale. Objectives: Present research will adapt the original ISS to a PRO format and make it more user-friendly, decrease scoring ambiguity, and improve item content to more accurately reflect present-day standards of MS care. Changes will be made through alterations in the order and scoring of responses, updates to grammar, phrasing, and terminology, and adjustments in scale criteria for levels of dysfunction. Additionally, the supplemental questionnaire on sexual dysfunction has been replaced with the well-validated and highly efficient 15-item Multiple Sclerosis Intimacy and Sexuality Questionnaire (MSISQ-15). This study will attempt to validate the ISS-2 and evaluate a newly proposed second-ary scoring method designed to predict EDSS score by grading ISS-2 items in grouped functional systems modules. Methods: ISS-2 will be normalized against the Patient-Determined Disease Steps (PDDS), a patient-reported measure of disability shown to correlate strongly with EDSS. Additionally, ISS-2 secondary scores will be regressed against patients’ current EDSS scores. Patient data are to be collected from the Multiple Sclerosis Center at Holy Name Medical Center in Teaneck, NJ. Results: None. Conclusions: None.

Supported by: NoneDisclosure: Jeffrey G. Portnoy, Marnina B. Stimmel, Sara Flood, Gabriel Hoff-nung, Mary Ann Picone, Lisa Glukhovsky, Jessica H. Sloan, Roseann Archetti, Eliana Pasternak, Jason Botvinick, Elana Mendelowitz: Nothing to disclose. Fred-erick W. Foley: Bayer (consulting fees).Keywords: Management of activities of daily living in MS, Minimal Record of Disability, MS and the caregiver/family

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percentage of patients reporting no side effects (43.8%) was higher than that reported in the clinical literature.

Supported by: Biogen IdecDisclosure: Terrie Livingston, Brieana Bukley: Biogen Idec (salary). Francis Staskon, Mark Matusik, Janeen DuChane: Nothing to disclose.Keywords: Comprehensive care and MS, Disease-modifying treatments in MS, Epidemiology of MS

(QL18) CONNECTED CARE FOR MULTIPLE SCLEROSIS: IMPROVING ADHERENCE WITH MANAGED THERAPY FOR PATIENTS WITH INDICATIONS OF FATIGUE OR DEPRESSIONFrancis Staskon,1 Rick T. Miller,2 Janeen DuChane,1 Mark Matusik1

1Health Services and Outcomes Research, Walgreen Co, Deerfield, IL; 2Specialty Clinical Services, Walgreen Co, Carnegie, PA

Background: Walgreens Connected Care for MS (CCMS) pro-gram provides enhanced management for patients taking multiple sclerosis (MS) medications to improve adherence and was updated in 2013 to assist those taking delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF; TECFIDERA) for relapsing forms of MS. The program includes assessments of patient-reported side effects and standardized screenings for depression and fatigue. Objectives: Examine 9-month adherence levels in relation to the duration of a patient’s managed status and patient-reported depres-sion and fatigue, controlling for demographics, medication comor-bidities, reported drug side effects, and starter dosage. Methods: Adherence was measured using PDC (proportion of days covered) for a 9-month follow-up period from index date. Patient-reported side effects and screenings for depression or fatigue were col-lected through the CCMS assessments. The study population included Walgreens Central Specialty patients, 18 years or older, initiating therapy between April 2013 and December 2013, and followed through June 2014. Mixed model analysis controlled for patient age, gender, comorbidities, and prior use of MS medications, and exam-ined reported side effects, adjunctive medication use, starter dosage, and screening indications combined, and interaction of screenings with managed duration. There were 1153 patients with two or more DMF fills, not concurrently on antidepressants or amphetamines, and with CCMS assessment information. Results: Mean 9-month adherence improved by 42.4% when patients managed within 3 months in the program were compared to those managed over 9 months (P < .001). When patients had indications of depression or fatigue, adherence was significantly lower compared with those without positive screening results (P < .001). The interaction between managed duration and depression/fatigue indication was also sig-nificant (P < .04), in which patients managed within 3 months with a positive screen had a significantly lower PDC (−13.5%) compared with negative screen patients. However, patients managed over 9 months and with a positive screen no longer had a significantly lower PDC (−2.3%). Conclusions: The 9-month DMF adherence rate was significantly improved by the length of patients’ participation in CCMS, even for those with positive screening results of depression or fatigue. This study replicated and extended prior research indicating that medication therapy management for MS patients significantly increases adherence to biologic medications.

Supported by: Biogen IdecDisclosure: Nothing to discloseKeywords: Disease-modifying treatments in MS, Medication therapy manage-ment, Psychological issues and MS

(QL19) PERCEPTIONS ABOUT MULTIPLE SCLEROSIS AMONG HISPANIC AMERICANS: NEED FOR TARGETED MESSAGINGLilyana Amezcua,1 Ana Palomeque,1 Jose Aparicio,1 Leslie Tarlow,1 Annette M. Langer-Gould2

1Neurology, University of Southern California, Los Angeles, CA; 2Department of Research and Evaluation, Department of Neurology, Kaiser Permanente, Southern California, Pasadena, CA

their EHRs. Research topics and study proposals are solicited, devel-oped, and approved through processes that incorporate input from iConquerMS participants and ensure scientific rigor and feasibility. To ensure that iConquerMS remains “patient-powered,” people with MS constitute the majority of members of the governance structure of iConquerMS. Results: As of mid-January, after a “soft” launch, iConquerMS membership is 590 individuals. The governance struc-ture includes people with MS, researchers, and representatives from other MS advocacy organizations. Policies and processes supporting iConquerMS research activities are being developed, and outreach to the research community is under way. Conclusions: iConquerMS is an initiative by and for people with MS who understand the need to contribute their ideas and health data to fuel medical research. iConquerMS offers people living with MS an opportunity to drive research on topics that matter most to them and represents a bridge connecting people with MS to the research community. Data collect-ed via iConquerMS will enable insights into a wide variety of topics, such as symptoms, treatment outcomes, and quality of life, and could lead to improved diagnoses, better treatments and, ultimately, cures for MS.

Supported by: PCORIDisclosure: Nothing to discloseKeywords: Complementary/alternative therapies in MS, Disease-modifying treat-ments in MS, Epidemiology of MS

(QL17) MULTIPLE SCLEROSIS PATIENT ADHERENCE TO DELAYED-RELEASE DIMETHYL FUMARATE AND PATIENT-REPORTED SIDE EFFECTS FROM A SPECIALTY PHARMACY PROGRAMTerrie Livingston,1 Brieana Bukley,1 Francis Staskon,2 Mark Matusik,2 Janeen DuChane2

1Biogen Idec Inc, Weston, MA; 2Health Services and Outcomes Research, Walgreen Co, Deerfield, IL

Background: Biogen Idec’s delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF; TECFIDERA) oral medi-cation to treat multiple sclerosis (MS) became available in March 2013 for relapsing forms of MS. Walgreens Connected Care for MS (CCMS) program provides enhanced management and care for patients taking DMF, including assessments of patient-reported side effects and related information. Limited real-world evidence is cur-rently available for MS patients taking DMF. Objectives: The main objective was to describe 6- and 12-month adherence levels, after controlling for other factors. A secondary objective was to describe the prevalence of patient-reported side effects. Methods: Adher-ence was measured using PDC (proportion of days covered) for a 6- or 12-month follow-up period. Patient-reported side effects were collected through the CCMS telephonic assessments. 5279 patients were at least 18 years of age and initiated therapy from April 2013 to December 2013, and followed through June 2014. Results: The demographic profile of patients was similar to that of the national MS population. Median PDC for the 3319 patients with 6 full months of data was 92.9% (range 16.5–100). For these patients, adherence to other MS medications utilized prior to DMF was 90.1% (range 1.7–100). For the 1216 patients with 12 months of data, the median PDC was 82.2% (range 10.1–100). 214 (4.0%) patients switched from DMF to another DMT within 12 months; the proportion was significantly lower among patients reporting no side effects (P < .02). 4179 patients were asked at least one side effect question. The most common response was none (1830 or 43.8%), followed by reports of flushing (1790 or 42.9%) and abdominal pain (698 or 16.7%). For assessed patient relapse within the last 30 days, 107 reported a relapse (2.6%) after the first 62 days of therapy through end of study. Conclusions: In the first year after approval, the 6-month adherence rates for patients utilizing DMF were equivalent to those of other patients treated with a DMT prior to starting DMF. As observed with other chronic medication use, adherence was lower at 12 months. Adherence was influenced by patient charac-teristics and length of CCMS participation. Rates of patient-reported side effects were comparable to those seen in clinical trials, and the

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and the Pain Catastrophizing Scale (PCS). Results: Results showed a 39.70% reduction in the PCS. Participants also had improvements of 30.25% and 45.24% in their MSQOL-54 Physical Composite Score and Mental Health Composite Score, respectively. Conclu-sions: The mindfulness-based meditation group for clients with MS at SMH appears to be an effective adjunct to conventional treatment in reducing clients’ perceived pain and increasing their QOL.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Mindfulness meditation, Psychological issues and MS

(QL21) UNDERSTANDING THE NEEDS OF HISPANIC/LATINO INDIVIDUALS AND FAMILIES AFFECTED BY MULTIPLE SCLEROSISCraig D. WesleyAdvocacy, Services, and Research, National Multiple Sclerosis Society, New York, NY

Background: The National Multiple Sclerosis Society gathered information and feedback from Hispanic/Latino individuals and families affected by multiple sclerosis (MS) to better understand their needs and to connect them to the resources and information they need to live their best lives. The outreach included Spanish-speaking focus groups and an online survey. Objectives: The purpose of the focus group and survey was to gather feedback about the specific type of content, information, and resources that would be most help-ful to Hispanic/Latino individuals living with MS to allow them to live their best lives. Methods: Focus groups were conducted in six markets across the country: Chicago, El Paso, Los Angeles, Miami, New York, and San Antonio. The online survey was disseminated to approximately 2000 Hispanic/Latino individuals living with MS to seek additional feedback from the community. Results: A total of 65 people, representing individuals with MS and their families, partici-pated in the focus groups. 116 individuals responded to the online survey. Participants indicated that information about how to manage symptoms, research updates about MS, and understanding treatment options would be the most helpful in managing their lives with MS. Participants indicated that educational materials and resources are not readily available in Spanish. Conclusions: From the survey outreach we learned that there are unique challenges that affect His-panic/Latino families affected by MS relating to accessing informa-tion in Spanish about the disease, treatment options, and how best to manage their MS symptoms. As a result of the survey outreach, the Society will drive the development and implementation of a strategic plan to address the unique challenges and to expand connections with the Hispanic/Latino community.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Management of activities of daily living in MS, MS and the care-giver/family

(QL22) EMPLOYMENT REGISTER OF PATIENTS ON NATALIZUMABCatherine B. Wingrove

Neurology, Sunderland Royal Hospital, Sunderland, United Kingdom

Background: The MS Society report “A Lottery of Treatment and Care—MS Services across the UK” was based on questionnaires from 10,530 patients. This report found that many people with MS can and want to work, but only one in four people with MS who are of working age are employed, compared with three out of four of the wider UK population. The report found that in two out of three cases, MS undermines employment and career opportunities and that, on average, a person with the condition misses out on 18 years of working life. Objectives: To compare the employment status of Sunderland patients on natalizumab with employment status as reported by the MS Society. Methods: Patients are routinely asked their employment status, which is then known by the MS nurse spe-cialist. Results: There are currently 30 patients on natalizumab: 20 men and 10 women. 93% of all working-age patients are employed, compared with 25% nationally. 100% of patients aged 18 to 30 are

Background: We have previously reported that Hispanics with mul-tiple sclerosis (MS) who have low levels of acculturation are at higher risk of disease progression. Little is known of the attitudes and beliefs about the cause of MS in this group. Objectives: N/A. Methods: We surveyed a cohort of Hispanics in Southern California. Using data from two focus group responses and questionnaires, we charac-terized perceptions about the causes of MS into environmental, bio-logical, and sociocultural. Results: Of the 97 responders, most were female (63%) and had some college education (61%), and the mean (SD) disease duration was 5.7 (6.7) years. Most perceived MS to be caused by an environmental factor such as stress (44%), with stress being significantly more common in individuals with higher levels of acculturation (81% vs. 60%, P = .01). Experiencing strong emo-tions such as fear (16%) or sadness and depression (11%) was also thought to precipitate MS. Fear was significantly more commonly reported in individuals with low levels of acculturation (30% vs. 9%, P = .04), while sadness showed no difference (15% vs. 9%, P = .46). Biological causes such as inheriting the disease showed no difference by acculturation (P = .17). Conclusions: Stress and cultural factors are commonly perceived causes of MS. Health education interven-tions are needed to reduce misconceptions and increase awareness of MS in Hispanics.

Supported by: NoneDisclosure: Lilyana Amezcua: Acorda, Novartis (advisory board, grant/research support); Biogen, Questcor (advisory board); Genzyme, Teva (consulting fees). Ana Palomeque, Jose Aparicio: Nothing to disclose. Leslie Tarlow: Acorda, Biogen Idec, Genzyme, Novartis, Questcor (consulting fees); International Organization of MS Nurses (mentor). Annette M. Langer-Gould: Biogen Idec, National Insti-tutes of Health, National Multiple Sclerosis Society (grant/research support).Keywords: Acculturation, Comprehensive care and MS, Management of activi-ties of daily living in MS

(QL20) MINDFULNESS-BASED MEDITATION FOR INDIVIDUALS WITH MULTIPLE SCLEROSIS IN THE MULTIPLE SCLEROSIS CLINICCecilia Wan

MS Clinic, St. Michael’s Hospital, Toronto, ON, Canada

Background: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that has an impact on the client’s physical, cognitive, functional, and emotional status. Pain (physical, emotional), limb weakness, fatigue, sensory changes, and depression and anxiety are commonly reported symptoms that negatively affect the individual’s psychological functioning and overall quality of life (Grossman et al., 2010). Mindfulness is the awareness that arises when we pay attention, nonjudgmentally, to what is happening in the present moment (Gardner-Nix & Costin-Hall, 2009). Mindfulness meditation has been used in a variety of treatments (ie, for coping with chronic pain, depression, and anxiety), and mindfulness training for individuals with MS has been shown to enhance quality of life, alleviate symptoms of depression, anxiety, and fatigue, and improve physical balance (Grossman et al., 2010; Mills & Allen, 2000). Objectives: To determine the impact of a mindfulness-based medi-tation group for clients with MS at the St. Michael’s Hospital (SMH) in Toronto, Canada, who have reported pain (chronic, neuropathic, emotional), fatigue, stress, and symptoms of depression and anxiety. Methods: Two 11-week mindfulness-based meditation programs were implemented between April–June and September–November of 2014. This program utilizes the Mindfulness-Based Chronic Pain Management (MBCPM) curriculum developed by Dr. Jackie Gardner-Nix, a staff physician at SMH. Clients met once a week for 2 hours and 15 minutes each to discuss a variety of topics (ie, judging, mind-body connection) and to practice multiple types of meditations (ie, body scan, guided imagery). 24 clients (11 from the first cycle and 13 from the second cycle) participated. Clients who failed to complete the post-questionnaires and/or those who completed less than four classes were excluded, resulting in 13 participants. Demo-graphic information was collected at baseline. Pre and post data were collected using the MS Quality of Life (MSQOL)-54 instrument

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Posters: Rehabilitation

influence muscle performance in people with MS who are nonambu-latory. Exercise may affect muscle oxidative capacity and function. This may be an important consideration when prescribing exercise and choosing interventions for people with MS who are nonambula-tory. The relationship between exercise and muscle oxidative capac-ity requires further investigation in people with MS.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Rehabilitation in MS

(RH08) CRITICAL FALLS AMONG PEOPLE AGING WITH MULTIPLE SCLEROSIS: GETTING HELP AFTER A FALLEtienne J. Bisson,1 Elizabeth Peterson,2 Marcia Finlayson1

1School of Rehabilitation Therapy, Queens University, Kingston, ON, Canada; 2Occupational Therapy, University of Illinois at Chicago, Chicago, IL

Background: Although falls among people with multiple sclerosis (MS) are common, critical falls, defined as falls with an inability to regain upright posture, have not been examined in this population. The inability to get up is associated with decline in activities of daily living (ADLs), serious injury, fear of falling, and even death among older adults. Among people with MS, the contribution of critical falls to fall-related morbidity and mortality is unknown. Objectives: The aim of this study was to determine the proportion of fallers receiving help to get up after a fall, and factors associated with critical falls among people with MS. The study was a secondary analysis of a national, United States–based, cross-sectional descriptive study of people with MS. Methods: Of the 354 people with MS aged ≥55 years interviewed, 322 reported a story about their most recent fall that included information about the consequences of falls and fall-related experiences (eg, need for assistance to get up after a fall). Data were analyzed descriptively to determine the proportion of fallers receiving help to get up after a fall. Logistic regression was performed to determine factors associated with receiving help to get up after a fall. Age, sex, and other covariates significantly associated with receiving help to get up during initial univariate analysis were considered for the model: live with others, disease duration, number of mobility aids used, fear of falling, fall leading to a fracture, and two MS symptoms: problems with balance or mobility and leg weak-ness. Results: A total of 177 fallers (54.1%) received help to get up after their most recent fall. Logistic regression analysis revealed six factors associated with receiving help: being female (odds ratio [OR] = 1.96, 95% confidence interval [CI] = 1.11-3.46), longer disease duration (OR = 1.04, CI = 1.01-1.06), lives with others (OR = 2.48, CI = 1.37-4.48), fall leading to fracture (OR = 4.21, CI = 1.27-13.99), problems with balance or mobility (OR = 1.90, CI = 1.03-3.50), and leg weakness (OR = 2.136, 95% CI = 1.133-4.027). Conclusions: More than half of people with MS received help after a fall, suggesting that critical falls in this population are common. Findings support the need for caregiver education on fall manage-ment, including content designed to help people with MS effectively direct others in how to assist them after a fall, as well as balance and strength training for people with MS to increase the ability to get up safely after a fall. Prospective studies involving people with MS are needed to better understand contributors and the consequences of critical falls.

Supported by: National Multiple Sclerosis Society, Retirement Research Founda-tion (grant RRF 2004-065)Disclosure: Etienne J. Bisson, Elizabeth Peterson: Nothing to disclose. Marcia Finlayson: Taylor/Francis-CRC Press (royalty).Keywords: Accidental falls, Management of activities of daily living in MS, MS and the caregiver/family

(RH09) IMPROVING DETECTION OF DISEASE COURSE IN MULTIPLE SCLEROSIS: AN ALTERNATIVE PATIENT-REPORTED OUTCOMES–BASED STRATEGYGiampaolo Brichetto,1 Samuele Fiorini,2 Andrea Tacchino,1 Michela Ponzio,1 Annalisa Barla,2 Alessandro Verri2

1Scientific Research Area, Italian MS Society, Genoa, Italy; 2DIBRIS, University of Genoa, Genoa, Italy

working, compared with 54% nationally. 89% of patients aged 31 to 50 are working, compared with 42% nationally, and there are no Sunderland natalizumab patients in the older 51 to 65 group collated by the MS Society. 25 were working before starting natali-zumab, and 4 more found employment since starting natalizumab. 21 live fully independently. None require full-time care. Disease-mod-ifying treatment may positively influence the employment prospects for patients with MS, as indicated by abstracts from Sweden and Germany. In the United Kingdom the MS Society reports that four out of five people with MS become unemployed within 10 years of diag-nosis, and living with a disability often brings additional costs, rang-ing from simply getting out and about, to paying for help around the house, informal care and prepared meals, the cost of prescriptions (in England), or the extra costs of heating, specialist equipment, and transport. Conclusions: Sunderland Royal patients on natalizumab have a much better employment status than those reported in the MS Society “A Lottery of Treatment and Care” report, and currently no Sunderland patients on natalizumab have a requirement for full-time care. Prompt diagnosis and access to effective treatment may have helped to achieve this.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Disease-modifying treatments in MS, Economic issues and MS, Employment in MS

REHABILITATION

(RH07) FUNCTIONAL ELECTRICAL STIMULATION CYCLING AND MUSCLE OXIDATIVE CAPACITY IN TWO NONAMBULATORY PEOPLE WITH MULTIPLE SCLEROSISDeborah Backus,1,2 Blake Burdett,1 Laura Hawkins,2 Christine Manella,1 Mary Ann Reynolds,3 Kevin McCully3

1Multiple Sclerosis Institute, Shepherd Center, Atlanta, GA; 2Crawford Research Institute, Shepherd Center, Atlanta, GA; 3Department of Kinesiology, University of Georgia, Athens, GA

Background: People with multiple sclerosis (MS) who are nonam-bulatory are challenged by the negative impact of decreased mobil-ity on their health and function. Decreased mobility leads to decon-ditioning that can cause secondary conditions and further functional decline. Exercise has been shown to have positive effects on health measures in people with MS; however, options for exercise are limited in those who use a wheelchair. Functional electrical stimula-tion (FES) cycling is one intervention accessible to people who use a wheelchair. The use of surface electrodes to stimulate the leg muscles during cycling may provide enough exercise to induce changes in health measures. FES cycling does not appear to cause an increase in symptoms in people with MS. However, little is known about the effect of FES cycling on muscle in people with MS, who are known to have impaired central nervous system input as well as impaired mus-cle metabolism. Muscle response to FES cycling may provide insights to assist with exercise prescription for people with MS who are nonambulatory. Objectives: To describe differences in FES cycling performance and muscle oxidative capacity in two nonambulatory individuals with MS who participated in a 4-week FES cycling inter-vention. Methods: Participants were part of a larger trial in which they trained on an FES cycle 30 mins/day, 2 to 3 days/week for 4 weeks. FES cycling performance was collected during each session. Muscle oxidative capacity (mVO2) was measured in the right vastus lateralis muscle using near infrared spectroscopy before and after the FES cycling training program. Results: Both individuals safely exercised on the FES cycle for 4 weeks, without adverse events. Both presented with mVO2 lower than that in able-bodied individuals. One was able to increase time and resistance during cycling over the 4-week period. She also demonstrated greater mVO2 than the par-ticipant who was unable to improve cycling performance; she also had an increase in mVO2 after training, while the other participant showed a decrease. Conclusions: Muscle oxidative capacity may

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tion. Conclusions: At the end of 2013, the patient had functional improvement that increased her quality of life. She could chew better, learned to swallow, interacted with people, smiled, and showed spontaneous body movements.

Disclosure: Nothing to discloseKeywords: Comprehensive care and MS, Disease-modifying treatments in MS, Management of activities of daily living in MS

(RH11) HOW DOES FATIGUING ACTIVITY ALTER CENTRAL AND PERIPHERAL NEUROMOTOR PHYSIOLOGY IN PEOPLE WITH MULTIPLE SCLEROSIS? A SYSTEMATIC REVIEW OF THE LITERATUREJessica L. Ryan, Evan T. Cohen, Stephanie Muth

Department of Rehabilitation and Movement Sciences, Rutgers, The State University of New Jersey, Stratford, NJ

Background: The fatigue commonly reported by people with mul-tiple sclerosis (MS) is complex and multifactorial. One theorized con-tributor to this fatigue is a reduction in muscle strength and functional capacity. These changes may be a result, in part, of altered neuromo-tor physiology, and may be exacerbated during and after fatiguing motor activity. It has been theorized that both peripheral and central mechanisms contribute to activity-induced changes in neuromotor physiology found in people with MS. Changes in peripheral neuro-motor physiology include altered muscle contractile properties and prolonged action potentials. Changes in central neuromotor physiol-ogy include increased conduction time, altered cortical activation, and reduced voluntary activation. The implications and extent of how activity-induced fatigue affects neuromotor physiology in people with MS are not fully understood. Objectives: The purpose of this systematic review was to synthesize current knowledge about the effect of fatiguing activity on neuromotor physiology in people with MS compared with those without. Methods: A search of the Ovid MEDLINE (1996–current) database was performed in August 2014 to identify appropriate literature using the following keywords: mul-tiple sclerosis AND [muscle fatigue OR motor fatigue]. Articles were screened with the following inclusion criteria: experimental or quasi-experimental studies of a sample of people with MS that measured changes in neuromotor physiology with fatiguing motor activity. Each article was then evaluated to determine the level of evidence using Sackett’s criteria. Results: Fifty-five articles were found through the search. Of these, seven articles met all criteria and were included in this systematic review. All seven articles received a Sackett level of evidence rating of 2b. Conclusions: In people with MS, central neural processes appear to be more affected by fatiguing activity than peripheral processes. Evidence for activity-induced differences in peripheral neuromotor physiology (eg, maximum volitional contrac-tion, twitch-evoked force production) between healthy people and those with MS is equivocal. However, activity-induced differences in central neuromotor physiology exist between these groups. People with MS have lower cortical activation levels and greater deficits in voluntary activation than those without MS. This suggests that inter-ventions that can improve central neuromotor drive may be more effective than those that target peripheral mechanisms to improve neuromotor function in people with MS.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Neuromotor physiology

(RH12) EXPLORING ROBOTIC-ASSISTED LOCOMOTOR TRAINING IN PHYSICAL THERAPY WITH MULTIPLE SCLEROSISSavanur Deepak Rajendra,1,2 Ryan Cardinal1,2

1Indiana Center for Advanced Neurorehabilitation, Indianapolis, IN; 2Neurorehabilitation and Robotics, IU Health, Indianapolis, IN

Background: Multiple sclerosis (MS) is a chronic inflammatory condition that causes multifocal demyelination along with astrocytic gliosis and axonal demyelination in the central nervous system. This

Background: Measuring multiple sclerosis (MS) is a difficult chal-lenge. The main difficulty is the variety of functional problems that may affect individual patients, so that no “typical” progression can be established, and no satisfactory “composite” indicators have been identified. Following recent guidelines, a methodological reflection is needed in order to develop a reliable core outcomes set. Objectives: The ongoing Italian MS Foundation (FISM) initiative on patient-reported outcomes (PROs) has the main objective of vali-dating a “functional profile” of MS based on meaningful variables and measures, useful to improve disease course detection, quantify disease progression, and identify the best disease predictors. Here, a proof of concept analysis is shown with the aim of detecting disease course. Methods: The clinical variables collected in the present study were based on functions sufficient to encompass the patient’s disability and to represent whole-person behaviors. The set of PRO and clinical scales selected were related mainly to mobility, fatigue, cognitive performance, emotional status, bladder continence, and quality of life. About 500 people with MS were enrolled in the study without any inclusion/exclusion criteria except MS diagnosis. The collected data were analyzed with machine learning methods, taking into account both unsupervised and supervised methods. Assuming that every measured variable does not have the same relevance, the main goal pursued was to find the real dimension of data, using tech-niques such as principal component analysis and k-means clustering. On the other hand, to tackle the problem of disease course detec-tion, a supervised problem was solved, in order to identify optimal models for disease progress discrimination based on linear classifiers such as Support Vector Machines. Results: The applied unsuper-vised techniques showed that the group of patients diagnosed as relapsing-remitting could be isolated from other clinical courses. Hence, supervised learning algorithms were applied to discriminate this group from the others. The best model reached median Matthews correlation coefficient precision and recall of 0.610, 0.874, and 0.820, respectively. Conclusions: The preliminary results suggest that the disease course could be inferred from PRO with a reasonable level of confidence and further improvements may be achieved in this context.

Disclosure: Nothing to discloseKeywords: Epidemiology of MS, MS prediction, Natural history of MS

(RH10) CASE REPORT: MULTIDISCIPLINARY APPROACH TO PATIENT WITH MULTIPLE SCLEROSIS, WITH TOTAL DEPENDENCEAna M. Canzonieri, Liliana Russo, Maria C. Giacomo, Ariane F. Buck

Research, ABEM–Brazilian Multiple Sclerosis Association, São Paulo, Brazil

Background: This case concerns a 55-year-old woman with sec-ondary progressive multiple sclerosis (MS)—a chronic, inflammatory, demyelinating, and progressive disease—of 9 years’ duration, who was using interferon beta-1a. She had an Expanded Disability Status Scale (EDSS) score of 7.5, used a wheelchair, used adult diapers, and was totally dependent on caregivers. Objectives: To demon-strate the clinical course of patients with MS with multidisciplinary intervention. Methods: The patient was tracked by the multidisci-plinary social organization team in São Paulo in March 2013 after a home visit by medical and social workers. The patient began neurorehabilitative treatment. Results: Therapy was required to gain range of motion, reduce spasticity and tremor, and increase balance in the trunk. Dental restoration and scraping procedures were difficult to perform because of the patient’s severe pain, tremor, and difficulty keeping her mouth open. The use of water had to be avoided due to choking. Speech was hindered by episodes of choking with food and spit. Psychological and neuropsychological assessment did not show signs of depression, but changes in cognitive functioning, low self-esteem, and low motivation were found. Psychological and neu-ropsychological exercises were begun together with occupational therapy, but the patient continued to have difficulties with speech, understanding, reduction of right upper-limb movement, and left-arm spasticity and numbness, with impaired bimanual coordina-

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−0.707, P < .0001), physical functioning (r = −0.360, P = .0074), physical health–role limitations (r = −0.631, P < .0001), social func-tioning (r = −0.637, P < .0001), emotional well-being (r = −0.363, P = .0069), emotional problems–role limitations (r = −0.409, P = .0021), and pain (r = −0.566, P < .0001). In addition, MFIS was also significantly correlated with exercise endurance time (r = −0.557, P = .0017). However, MFIS was not significantly correlated with self-reported physical activity (PADS) (r = −0.187, P = .1764). Conclusions: Muscle fatigue and its perception have an impact on many aspects of quality of life, including physical health, social functioning, pain, and overall well-being. Importantly, self-reported fatigue was associated with objective measures of exercise endur-ance. These data suggest that MS patients’ perception of fatigue is an important part of their capacity to exercise. However, it is unclear why their self-reported fatigue was not associated with self-reported physical activity. It is likely that they tend to overestimate their amount of physical activity, since they appear to accurately report their fatigue.

Supported by: National Institute on Disability and Rehabilitation Research (grant H133G120081)Disclosure: Nothing to discloseKeywords: Exercise and MS

(RH14) WALKING WHILE TALKING: RELATIONSHIPS AMONG MOTOR-COGNITIVE DUAL-TASKS, FUNCTIONAL PERFORMANCE, AND STRUCTURAL MRINora E. Fritz,1,2 Jennifer Keller,2 Chen Chun Chiang,2 Allen Jiang,2 Peter A. Calabresi,3 Kathleen M. Zackowski1-3

1Physical Medicine and Rehabilitation, Johns Hopkins School of Medicine, Baltimore, MD; 2Motion Analysis Laboratory, Kennedy Krieger Institute, Baltimore, MD; 3Neurology, Johns Hopkins School of Medicine, Baltimore, MD

Background: Greater than 45% of individuals with multiple sclerosis (MS) report cognitive dysfunction, and 85% report gait dysfunction that interferes with daily functioning. Impairments in mobility and cognition contribute to declines in everyday activities that require simultaneous motor and cognitive functioning (eg, motor-cognitive dual-tasks; MCDT). Our laboratory has previously shown relationships among dynamic posturography and walking measures and among tract-specific measures of the brain corticospinal tract (CST) and walking measures in MS. Objectives: The objective of this study is to explore the relationships among motor function (ie, posturography, walking), cognitive function, MCDT ability, and tract-specific magnetic resonance imaging (MRI) measures. Methods: To date, 9 individuals with relapsing-remitting MS have volunteered for this study (mean ± SD age, 47.9 ± 14.9 years; symptom duration, 11.1 ± 6.1 years; gender, 7 females; Expanded Disability Status Scale [EDSS] median [range], 2.5 [1–4]). All subjects participated in motor and cognitive testing and a 3T MRI with both diffusion tensor (fractional anisotropy and mean diffusivity only) and magnetization transfer imaging. Correlation analyses were used to examine the relationships among clinical and MRI measures. Results: Better performance on dynamic posturography (increased anterior-posterior [AP] sway) is related to improved walking performance (r > 0.78; P < .01). Interestingly, individuals with increased AP sway also had better diffusivity of the CST (r = −0.86; P = 0.003). Similarly, individuals with less sway on static balance testing (r = −0.70; P = 0.036) and faster Timed Up and Go (TUG) performance demon-strated improved diffusivity of the CST (r = −0.67; P = .048). Poorer performance on cognitive testing (Symbol Digit Modality Test) was associated with slower performance on MCDT (r > 0.66; P < .05). Additionally, individuals with less AP sway perform worse on MCDT (r > 0.76; P < .02). Poor performance on balance dual-tasks was also associated with reduced diffusivity of the CST (r = −0.8667; P = .0025). Conclusions: Our preliminary data suggest that assess-ment of MCDT may be a useful addition to the clinical examination, as it provides information on both structural integrity and functional performance. Additionally, this work highlights the specificity of AP

results in neurologic symptoms including spasticity, resulting in gait, coordination, and balance impairments that lead to fatigue and a lack of physical activity. Traditional physical therapy (PT) is labor-intensive for both therapist and patient and requires high amounts of physical effort. Robotic-assisted locomotor training (RALT) is an emerging PT intervention that presents new opportunity for the MS population. RALT is the application of a robotic orthosis to facilitate gait training in a controlled and repetitive environment. RALT allows PTs to customize training parameters in MS to specific conditions that may potentially enhance outcomes. There is a growing body of evidence supporting the use of RALT in neurologic conditions such as stroke, TBI, and SCI. The ability to create training paradigms that focus on levels of repetition and intensity facilitates improved outcomes due to increased specificity and, potentially, neuroplasti-city. Studies by Straudi et al. (2013), Schwartz et al. (2012), and Beer et al. (2008) demonstrated short-term benefits following a RALT protocol, but no significant difference between RALT and conven-tional PT in long-term follow-ups. Furthermore, Gandolfi et al. (2014) demonstrated significant overall improvements at 1 month follow-up in walking, posture, and balance confidence. The studies cited have all suggested that further investigation is necessary to determine the long-term effect of RALT. Conclusions: Based on anecdotal evidence and clinical success with other neurologic conditions, we feel that RALT may prove to be a viable addition to a PT protocol for patients with MS. The customizable aspects of RALT therapy, namely control-ling body weight support and guidance force, allow patients to expe-rience increased amounts of repetitious walking prior to the onset of fatigue. In time, this training, when paired with other techniques such as strengthening and stretching, may lead to improved long-term out-comes. While the application of RALT in the MS population has thus far proved, if nothing else, equal to traditional PT, further research is needed to evaluate claims of improved outcomes.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Complementary/alternative therapies in MS, Robotic-assisted therapy in MS

(RH13) FATIGUE IS ASSOCIATED WITH EXERCISE ENDURANCE AND QUALITY OF LIFE BUT NOT SELF-REPORTED PHYSICAL ACTIVITY IN INDIVIDUALS WITH MULTIPLE SCLEROSISNadine M. Fisher, Andrew D. Ray

Rehabilitation Science, University at Buffalo, Buffalo, NY

Background: The fatigue experienced by individuals with multiple sclerosis (MS) can have an impact on many aspects of their lives, including activities of daily living and quality of life. Objectives: The objective of this study was to determine the association between self-reported fatigue levels, health-related quality of life, and the abil-ity to sustain a moderate level of exercise (endurance). Methods: MS patients (40 women, 13 men, n = 53) with a mean age of 51.6 ± 10.8 years (range 25–72 years), average Expanded Disability Status Scale (EDSS) score of 3.3 ± 1.9 (range 1.0–6.5), and 14.2 ± 9.4 years since diagnosis (range 1–35 years) participated in this study. Patients were included if they could continuously pedal a cycle ergometer for a minimum of 10 minutes at a light to moderate intensity. Testing occurred on 2 separate days, separated by 1 week to allow for recovery. On day 1, subjects completed the Modified Fatigue Impact Scale (MFIS) and a peak graded exercise test to voluntary exhaustion on a cycle ergometer. On day 2 subjects com-pleted the SF-36, Physical Activity and Disability Survey (PADS), and an endurance exercise test at 60% of the peak workload assessed on day 1. Data were analyzed for associations among the measured variables (Pearson product correlations) using SAS. Results: Sig-nificant correlations were shown between MFIS total score and SF-36 total score (r = −0.582, P < .0001), as well as the subscales of the SF-36: general health (r = −0.540, P < .0001), energy/fatigue (r =

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to become more physically active, and the Internet is the preferred medium. Objectives: To investigate what people with MS would like from a web-based resource to encourage exercise and physical activity. Methods: Three focus groups (n = 22) and 11 semistruc-tured interviews were conducted. Participants had Patient-Determined Disease Steps (PDDS) scores ranging from 0 to 7 with a mean of 3.1. Interviews were audiorecorded and transcribed verbatim, and thematic content analysis was performed. Results: The themes extracted from the data were 1) content, 2) format, 3) accessibility, and 4) interactivity of the resource. Participants believed the web resource to be a good idea and suggested that the content of the resource should include a focus on knowledge of the benefits of being physically active while also illustrating the types of exercise in which people with MS could participate. Ensuring information was stratified by mobility level and that the resource was interactive, por-traying a “sense of community” and use of success stories, was also suggested by participants. Conclusions: The “Activity Matters” proj-ect will develop a web resource that aims to enable people with MS to become more physically active using these data and input from a range of stakeholders.

Supported by: Irish Research Council, MS Ireland, through the Ireland Fund, MS IrelandDisclosure: Blathin Casey: MS Ireland (grant/research support). Sara Hayes: Health Research Board (grant/research support). Catherine M. Browne: Irish Research Council (grant/research support). Aidan Larkin, Susan B. Coote: Noth-ing to disclose.Keywords: Comprehensive care and MS, Management of activities of daily living in MS, Physical activity

(RH18) WITHDRAWN

(RH19) THE DEVELOPMENT OF A HAND ASSESSMENT FOR MULTIPLE SCLEROSISLuisa C. Johnson, Lauren K. Braun, Sinead Hynes, Susan Forwell

Department of Occupational Science and Occupational Therapy, University of British Columbia, Vancouver, BC, Canada

Background: Hand function, such as grip strength, unimanual and bimanual coordination, and sensation, is often compromised in individuals with multiple sclerosis (MS). Impairment in these domains affects one’s ability to complete self-care, productivity, and leisure activities, thereby affecting independence and quality of life. Until now, no single performance hand assessment specific to MS had been developed. Objectives: 1) To describe a comprehensive, performance-based, client-centered hand assessment, designed to identify hand function difficulties for people with MS and to guide intervention decisions. 2) To evaluate clinimetrics of this assessment, including feasibility, clinical utility, and content validity. Methods: This study is conducted in two phases: assessment development, and then refinement and evaluation. This assessment was developed based on the literature and experience assessing hand function dif-ficulties among people with MS. Refinement and evaluation included an initial consultation phase with clinician participants who made suggestions, and the assessment was revised. This version was then administered to people with MS to test the instrument’s clinimetrics. Results: 1) The developed Hand Assessment for Multiple Sclerosis (HAMS) includes both an activity and environment questionnaire and a physical and performance-based component that evaluates a) muscle strength (grip and pinch), b) peripheral sensation (light touch and stereognosis), c) vibration, and d) coordination (unimanual and bimanual). 2) In terms of content validity, the overall impression of clinicians was favorable, with minor suggestions included in the revision of the assessment. The HAMS was shown to be feasible and is establishing criterion validity. Conclusions: This comprehensive assessment provides practitioners with an efficient yet comprehensive assessment of hand function that directs appropriate treatment plan-ning for people with MS. This study builds practice knowledge with the development and application of a novel client-centered hand

sway as a marker for walking function and provides new evidence of the relationship of dynamic posturography to MCDT performance and CST integrity. Future work will include exploration of additional brain tracts.

Supported by: National Multiple Sclerosis SocietyDisclosure: Nora E. Fritz, Jennifer Keller, Chen Chun Chiang, Allen Jiang: Nothing to disclose. Peter A. Calabresi: AbbVie, Prothena, Vaccinex, Vertex (consulting fees); Biogen Idec, MedImmune, National Multiple Sclerosis Society, Novartis (grant/research support). Kathleen M. Zackowski: Biogen Idec, National Multiple Sclerosis Society (grant/research support).Keywords: Balance, Imaging and MS

(RH15) COMPLIANCE IN REHABILITATION WITH MULTIPLE SCLEROSIS PATIENTSDori Goldman, Jennifer Kalina

MS Comprehensive Care Center, NYU Langone Medical Center, New York, NY

Background: People with multiple sclerosis (MS) have a wide range of rehabilitative needs, including occupational therapy (OT). Despite these needs, in a population of over 2500 people attending an outpatient MS center, compliance with attending OT treatment sessions has been shown to be problematic. Literature on noncom-pliance for OT in the general population is available; however, no literature could be found specifically for the MS population. Objec-tives: To investigate the incidence of noncompliance for outpatient OT at an urban specialty MS comprehensive care center. Methods: A database search of all scheduled OT visits at an urban MS cen-ter was conducted over a 6-month period using electronic record software. Total number of scheduled OT visits included those who attended their OT visit, those who canceled their visit within 3 days of their appointment, and those who did not attend their appoint-ment without any notification (“no show”). Noncompliance rates were calculated based on the total number of cancellations and no show rates, divided by the total number of scheduled OT visits in a given month. This information was then compared to noncompliance statistics of general neurologic OT visits at an urban outpatient facil-ity. Results: The search revealed the following OT noncompliance rates at an MS center: July, 33%; August, 24%; September, 28%; October, 33%; November, 42%; December, 30%. This compares to the general neurologic OT noncompliance rates at a rehabilitation center: July, 19%; August, 22%; September, 25%; October, 18%; November, 23%; December, 23%. Noncompliance rates at the MS center are higher on average by 10%, ranging from 2% to 19% differences. Reasons for cancellations and “no shows” are currently being analyzed. Conclusions: Compliance with OT attendance is crucial to reaching therapeutic gains. However, compliance with OT attendance in the MS population has not yet been addressed in the MS literature and appears to be problematic compared with OT in a general rehabilitation population. Additional research is necessary to determine reasons for noncompliance in order to improve treatment compliance as well as therapeutic gains.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Management of activities of daily living in MS, Rehabilitation

(RH16) WITHDRAWN

(RH17) WEB-BASED PHYSICAL ACTIVITY RESOURCES: LISTENING TO THE VOICE OF PEOPLE WITH MULTIPLE SCLEROSISBlathin Casey,1 Sara Hayes,2 Aidan Larkin,3 Catherine M. Browne,1 Susan B. Coote1

1Department of Clinical Therapies, University of Limerick, Limerick, Ireland; 2University of Limerick, Limerick, Ireland; 3Multiple Sclerosis Society, Galway, Ireland

Background: The positive effects of exercise for people with mul-tiple sclerosis (MS) are well established. Despite this, people with MS are largely inactive and at risk due to sedentary lifestyles. People with MS have indicated a need for more information to enable them

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day of a score of greater than 0 per mouse. Mice were euthanized 29 days after induction. Brains and spinal cords were taken for histologic analysis, phenotype of CNS infiltrating lymphocytes using flow cytometry, and PLP-specific responses from isolated CNS-ILs by ELISA. Results: The incidence of EAE did not differ between seden-tary (14/16; 88%) and exercise (14/15; 93%) groups. There was a day by condition interaction on percent change in body weight (F1,28 = 1.920, P < .05), but not EAE disability score (F1,28 = 1.179, P = .25). There was no condition main effect (F1,9 = 0.016, P = .901), but there was a day main effect (F1,28 = 7.785, P < .05) whereby EAE disability changed in a predictable pattern over the 29-day period. There was no significant difference in peak disability score between groups (P = .95). There was a significant difference in the day of disease onset such that mice in the wheel running group dem-onstrated disability scores earlier compared with the sedentary group (P < .05). There were no differences between groups in the percent-age of infiltrating CD3+ T cells, CD19+ B cells, or CD11b+CD45hi macrophages or the percentage of Th1 cells isolated from the CNS. Conclusions: Our findings provide evidence that voluntary exercise minimally impacts disability and disease course in mice with relaps-ing-remitting EAE. We believe a repeated study that is extended for a longer period of time post induction is necessary in order to elucidate the possible longer-lasting effects of exercise on EAE.

Supported by: NoneDisclosure: Rachel E. Klaren, Andrew J. Steelman, Brandt Pence, Jeffrey A. Woods: Nothing to disclose. Robert W. Motl: Biogen, Acorda (consulting fees, grant/research support); EMD Serono (fees for non-CME services from commercial interests or their agents).Keywords: CNS repair, Disease-modifying treatments in MS, Immunology and MS

(RH22) USE OF THE MULTIPLE SCLEROSIS COGNITIVE-LINGUISTIC CHECKLIST AND THE BRIEF INTERNATIONAL COGNITIVE ASSESSMENT FOR MULTIPLE SCLEROSIS: GENERATING PATIENT-CENTERED GOALSLori A. Kostich

Outpatient Rehabilitation, Mandell Center for Multiple Sclerosis Treatment and Research, Hartford, CT

Background: Speech-language pathologists (SLPs) are responsible for identifying and providing care for people with multiple sclerosis (MS) with deficits in cognitive-linguistic function. The patient-centered model of care includes the patient’s concerns in the development of the plan of care and input into treatment goals. The Multiple Sclerosis Cognitive-Linguistic Checklist (MSCLC) is a patient-centered report-ing tool that identifies specific examples of functional challenges at home, at work, and in the community. Patient report alone is subjec-tive and difficult to quantify. The Brief International Cognitive Assess-ment for Multiple Sclerosis (BICAMS) consists of three published standardized tests chosen by a consensus panel, which provides a reliable and objective measure of deficit in processing speed and visual/auditory encoding. Alone, the BICAMS does not identify specific examples of the functional ramifications of these objective deficits. Utilizing the MSCLC as a complement to the BICAMS is a method developed by the PI to gain repeatable objective evidence of deficit and patient-centered data to generate meaningful, measurable goals. Objectives: 1) To show prevalence of deficit in attention, memory, and word retrieval complaints in the caseload of the SLP. 2) To show use of the BICAMS and MSCLC evaluation tools together to generate measurable and meaningful cognitive-linguistic goals. Methods: 1) At evaluation the patient reports deficit in attention, memory, and/or word retrieval. 2) The BICAMS is administered. Patients who are identified as appropriate for treatment based on level of deficit are offered treatment of specific duration and frequen-cy. 3) Patients appropriate for treatment complete the MSCLC. 4) The SLP writes goals based on deficit established by BICAMS, reflecting the patient concerns identified in the MSCLC. Results: Sample Case Study: Patient: A teacher experiencing difficulty completing work

assessment for people with MS who experience hand impairment. Additionally, assessment results help to enlighten clients about their current hand function, provide information to tailor appropriate treat-ment planning, and direct future interventions.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Comprehensive care and MS, Management of activities of daily living in MS

(RH20) IMPAIRMENT AND DISABILITY IN PEOPLE WITH MULTIPLE SCLEROSIS: DO FUNCTIONAL PERFORMANCE OR FUNCTIONAL LIMITATIONS MATTER?Rachel E. Klaren, Lara A. Pilutti, Brian M. Sandroff, Robert W. Motl


Background: People with multiple sclerosis (MS) often demonstrate impairment in cardiorespiratory and musculoskeletal systems that may be associated with functional performance, functional limita-tions, and disability limitations. Objectives: This study examined such relationships in people with MS using Nagi’s disablement model and its subsequent conceptual modifications. Methods: The sample included 63 people with MS (75% relapsing-remitting MS, median Expanded Disability Status Scale [EDSS] score = 4.0, mean MS duration = 13.1 years) who underwent measurements of aerobic fitness and muscular strength (ie, impairment), functional per-formance, functional limitations, and disability limitations. The data were primarily examined using path analysis in Mplus 7.0. Results: Our final model provided an excellent fit for the data (χ² = 0.67, df = 3, P = .88, standardized root-mean-square residual [SRMR] = .01, comparative fit index [CFI] = 1.00). The final model indicated that aerobic fitness and muscular strength were indirectly associated with disability limitations in people with MS through a pathway that included functional limitations (indirect path coefficients of 0.29 and 0.20, respectively), but not functional performance. Conclusions: Aerobic fitness and muscular strength may be important targets of exercise training interventions for improving perceived functional limi-tations and disability limitations in people with MS.

Supported by: National Multiple Sclerosis Society (IL 0003)Disclosure: Rachel E. Klaren, Brian M. Sandroff: Nothing to disclose. Lara A. Pilutti: National Multiple Sclerosis Society (grant/research support). Robert W. Motl: Biogen, Acorda (consulting fees, grant/research support); EMD Serono (fees for non-CME services from commercial interests or their agents).Keywords: Complementary/alternative therapies in MS, Management of activi-ties of daily living in MS

(RH21) EFFECTS OF VOLUNTARY EXERCISE ON THE PATHOGENESIS OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITISRachel E. Klaren,1 Andrew J. Steelman,2 Brandt Pence,1 Jeffrey A. Woods,1 Robert W. Motl1

1Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL; 2University of Illinois at Urbana-Champaign, Urbana, IL

Background: Little is known about the effects of exercise using experimental autoimmune encephalomyelitis (EAE). Some evidence suggests that exercise during EAE may attenuate disease onset and severity. However, to our knowledge, no research exists on the effects of voluntary exercise in the relapsing-remitting model of EAE. We believe this to be important, as the majority of people diagnosed with MS demonstrate a relapsing-remitting clinical course. Objectives: We investigated the effects of voluntary exercise (ie, wheel running) on disability scores and pathogenesis in mice during disease onset and course of a relapsing-remitting EAE model. Methods: 31 female SJL/J mice were subcutaneously injected with the encephalitogenic myelin antigen proteolipid protein (PLP) 139-151 emulsified in Com-plete Freunds Adjuvant (CFA). Mice were then randomly assigned to either voluntary exercise (ie, wheel running; n = 15) or sedentary (n = 16) groups. Mice were weighed and scored daily for EAE dis-ability using a blinded rater. Disease onset was recorded as the first

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(RH24) PROLONGED-RELEASE FAMPRIDINE AS ADJUNCT THERAPY TO ACTIVE ENABLED MOTOR TRAINING IN MULTIPLE SCLEROSIS PATIENTS: A PILOT, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDYFrancois H. Jacques,1,2 Adrian J. Schembri,3 Avi Nativ,2 Chantal Paquette,1 Pawel Kalinowski3

1Clinique Neuro-Outaouais, Gatineau, QC, Canada; 2Clinique NeuroGym, Gatineau, QC, Canada; 3Cogstate, Melbourne, Australia

Background: Walking impairment is a prominent manifestation of multiple sclerosis (MS). Up to 85% of MS patients identify it as their primary complaint. Prolonged-release fampridine (PRF) has been shown in MS patients to improve walking capabilities as measured by the Timed 25-Foot Walk test. The effect of PRF on the benefit of exercise in MS has never been studied. Objectives: To investigate whether MS subjects treated with PRF 10 mg bid will show a greater benefit from active enabled motor training as compared with sub-jects treated with placebo. Methods: Single-center, phase 4, pilot, placebo-controlled, double-blind 18-week study. 30 MS patients of all types who satisfied PRF’s product monograph prescribing criteria were recruited. Half of the patients were randomized to receive PRF 10 mg bid and the other half received placebo bid. All patients participated in active enabled motor training consisting of three sessions of 1 hour per week for a period of 6 weeks. All patients then continued taking their medication (PRF or placebo) during a subsequent observational period of 8 weeks. Patients were evalu-ated at times −4, 0, 6, and 14 weeks using the timed 8-Meter Walk (8MW), the 6-Minute Walk (6MW), and the timed Sit-to-Stand (STS). Results: Both groups were balanced at baseline. The PRF-treated group achieved a higher mean percent improvement from baseline in all three tasks at both the 6- and 14-week time points. The differ-ence reached statistical significance (mean difference of 14.29, P = .046) for the 8MW at the 14-week time point. A higher incidence of responders (>20% improvement from baseline) was seen in the PRF-treated group at 6 weeks on the 8MW (odds ratio [OR] 2.31) and the 6MW (OR 1.63) and at 14 weeks on the 8MW and the STS (OR 2.0). Conclusions: PRF in MS patients appears to enhance the benefit of active enabled motor training and to better sustain it over the following 8 weeks. Further studies are warranted.

Supported by: Biogen IdecDisclosure: Francois H. Jacques: Biogen Idec, Genzyme, Roche (infusion clinic); Biogen Idec, Sanofi, Novartis, Genzyme, Merck Serono, Roche, GSK (consulting fees, grant/research support); Clinique NeuroGym (ownership interest). Avi Nativ: Clinique NeuroGym (ownership interest). Adrian J. Schembri, Chantal Paquette, Pawel Kalinowski: Nothing to disclose.Keywords: Comprehensive care and MS, Rehabilitation

(RH25) INTERRATER RELIABILITY OF MINI-BESTEST IN AMBULATORY PEOPLE WITH MULTIPLE SCLEROSISElaine O. Ross


Background: Balance impairments are common and complex in people with multiple sclerosis (MS). Current balance measures do not consider many of the components required for functional balance. A novel test, the Mini-BESTest (MBT), may be more clinically useful, as it considers additional balance domains. To the best of the authors’ knowledge, no literature has investigated the interrater reliability of the MBT exclusively in ambulatory people with MS. Objectives: To investigate the interrater reliability of the MBT in ambulatory people with MS. Methods: A sample of convenience (n = 52) was recruit-ed. All participants were outpatients referred for physiotherapy with a primary diagnosis of MS, medically stable, older than 18 years of age, and able to ambulate independently with or without an aid. Participants’ demographic data were collected prior to completing the MBT with rater 1 (R1). Rater 2 (R2) then repeated the MBT. Statis-tical analyses were undertaken using IBM SPSS Statistics version 20. Results: The mean MBT scores of R1 and R2 were 19.1 (SD 5.75)

requirements. BICAMS: SDMT: 1.0 SD below mean; CVLT2: 1.5 SD below mean; BVMTR: 1.0 SD below mean. Response on MSCLC: Increased difficulty returning to task once distracted by nonroutine events at work such as colleagues walking into the room, fire alarms, misplaced material. At home, phone calls, dogs barking, and chil-dren squabbling draw the patient off-task. Sample Goal: The patient will repeat 7 units of information in the correct order after 2 to 3 dis-tractions to restore ability to return to task after distraction. Conclu-sions: 1) People with MS presenting for evaluation by SLPs identify complaints of cognitive-linguistic deficit. 2) Use of the MSCLC as a companion to the BICAMS is an effective method to objectively iden-tify level of cognitive deficits and subjectively identify the effect those deficits may be having on the daily routines of people with MS. 3) Using these data, meaningful and measurable patient-centered goals can be written by the SLP to restore specific function to the patient.

Supported by: St. Francis Healthcare Network BestCare Grant


Keywords: Comprehensive care and MS, Employment in MS

(RH23) HEALTH LOCUS OF CONTROL FROM A PHYSICAL PERSPECTIVE IN PATIENTS WITH MULTIPLE SCLEROSISTurhan Kahraman,1 Gorkem Kosehasanogullari,2 Sema Savci,1 Serkan Ozakbas3

1School of Physical Therapy and Rehabilitation, Dokuz Eylul University, Izmir, Turkey; 2Usak State Hospital, Usak, Turkey; 3Department of Neurology, Dokuz Eylul University, Izmir, Turkey

Background: Locus of control (LOC) is the patient’s belief in the location of control over the results of his/her behavior, which is a strategy in order to identify the cause of their own disease. Multiple sclerosis (MS) is a chronic disease with a progressive course and a high prevalence of accompanying disabilities. Because it has a deep impact on the patient’s life, LOC is fundamentally important in order to manage the MS patient properly. External beliefs of LOC could reduce the extent of personal efforts toward rehabilitation, and internal beliefs could increase the effects of rehabilitation with motivation and adherence. Surprisingly, however, LOC in people with MS has not been extensively investigated, particularly from a physical perspective. Objectives: The objective was to investigate the relationship between health LOC and physical status in people with MS. Methods: 108 people with clinically definite MS were randomly included in this cross-sectional study. LOC was measured with the Multidimensional Health Locus of Control Scale (MHLC), which includes three subscales to assess internal, powerful others external, and chance external LOC. Disability levels were determined with the Expanded Disability Status Scale (EDSS) by the same neu-rologist and with Patient-Determined Disease Steps (PDDS) by the patients. Perceived walking quality was evaluated with the 12-item Multiple Sclerosis Walking Scale (MSWS-12). The effect of fatigue on physical functioning was measured with the Fatigue Impact Scale (FIS)–Physical Subscale (PS). Results: There were 82 female (75.9%) and 26 male (24.1%) people with MS with a mean age of 39.96 ± 11.02 years. EDSS scores were between 0 and 6.5, with a mean of 2.19 ± 1.87. Chance LOC was correlated with all vari-ables: EDSS (r = 0.27, P < .05), PDDS (r = 0.32, P < .05), MSWS-12 (r = 0.29, P < .05), FIS-PS (r = 0.27, P < .05), and FIS-Total (r = 0.22, P < .05). Internal and powerful others LOC were not correlated with any variables (P > .05). Conclusions: Increased disability level and worse physical status were associated with more chance LOC. This means that people with MS tend to attribute their physical health status to chance rather than to events under their own and other people’s, such as health professionals’, control. These results suggest that modifications of control beliefs should be done to promote better rehabilitation effects and health outcomes.


Keywords: Management of activities of daily living in MS

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Multinomial logistic regression results indicated predictors of employ-ment, and participant ratings of 38 employment concerns determined factors influencing success in job acquisition and retention. Results: In comparisons between unemployed adults with MS and those employed full or part time, critical variables included gender, age, financial status, and severity and duration of MS. Compared to unemployed adults with MS, individuals employed part time were more likely to be female, younger, better educated, more financially secure, and less severely impaired by MS. Compared to unemployed adults with MS, adults with MS employed full time were more likely to be younger, better educated, more financially secure, with a shorter duration of MS, and with fewer cognitive and physical limitations. The following items received the highest importance and satisfaction ratings (ie, employment strengths): People with MS are encouraged to take control of their lives, have the same maternity and family leave options as other workers, are provided the same retirement benefits as other workers, and are made aware of employer expecta-tions in the same way as other employees. Items with high impor-tance but low satisfaction (ie, employment concerns) included the fol-lowing: People with MS understand the provisions of the Affordable Care Act, know how to discuss their job accommodation needs with their employers, can request a review of their accommodation needs without fear of retaliation, understand the employment provisions of the Americans with Disabilities Act As Amended, are considered for other jobs in the same company if their MS prevents them from returning to their former jobs, and understand the benefits of disclos-ing disability to their employers. Conclusions: Findings underscore the importance of the disease-demographics predictive model and the need for progressive worksite accommodations; educational and vocational training; ergonomic job modifications; and reasonable accommodation consultation at the workplace. Employment concerns data indicate that adults with MS need help understanding a) the pro-visions of national health insurance and disability civil rights legisla-tion, b) effective ways to disclose disability and request accommoda-tions so as to avoid retaliation from their employers, and c) strategies for identifying or developing job alternatives in the same company.

Supported by: National Multiple Sclerosis Society Health Care Delivery and Policy Research GrantDisclosure: Nothing to discloseKeywords: Employment in MS, Psychological issues and MS, Vocational reha-bilitation and MS

(RH28) A CLINICAL PATHWAY FOR THE EVALUATION AND TREATMENT OF FOOTDROP IN MULTIPLE SCLEROSISRobert J. Schreyer,1,2 Emil Euaparadorn,1,2 Herbert I. Karpatkin3

1Physical Therapy, Touro College, New York, NY; 2Physical Therapy, Aspire Center for Health and Wellness, New York, NY; 3Physical Therapy, Hunter College, New York, NY

Background: Although multiple sclerosis (MS) is a disease of the central nervous system, musculoskeletal impairments are a common cause of immobility. Footdrop is a common example, in which evalu-ation and treatment can be highly variable because of the disorder’s multifactorial nature. No clinical guidelines exist to address this limi-tation, leading to inconsistent approaches by clinicians. Formulaic, “one size fits all” approaches to footdrop often result in poor out-comes owing to a lack of appreciation of the multiple factors that can lead to this condition. Objectives: The purpose of this project is to provide a clinical pathway for clinicians to ensure that a comprehen-sive and reliable method is performed on all patients with MS. We hypothesize that the use of such a pathway will result in better man-agement of MS mobility deficits due to footdrop. If our hypothesis is correct, this pathway will result in therapists who treat MS having a more comprehensive and reliable set of tools to effectively manage individuals presenting with footdrop. Methods: This clinical path-way is a multifactorial assessment that directs a clinician through a comprehensive evaluation with treatments based on the results. The evaluation examines the various contributions of range of motion (ROM), strength, spasticity, sensation, and fatigue/endurance, taking

and 18.8 (SD 6.01), respectively. The mean difference between raters was 0.27 (SD 1.8; confidence interval [CI], −2.5 to 2.02; P = .816). The intraclass correlation coefficient (ICC) was 0.976 (CI, 0.92-0.97). The standard error of the measure (SEM) was 2.56. The minimum detectable change (MDC) of the MBT was calculated to be 7 points. Conclusions: Despite the high MDC shown in this study, the high ICC values suggest that there was strong agreement between two raters for the MBT in an ambulatory population with MS.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Balance

(RH26) COMPARISON OF THE BERG BALANCE SCALE AND THE MINI-BESTEST IN AMBULATORY PEOPLE WITH MULTIPLE SCLEROSISElaine O. Ross


Background: Balance is complex, and problems with balance are prevalent in people with multiple sclerosis (MS). The Berg Balance Scale (BBS) is a commonly used instrument, and the Mini-BESTest (MBT) is a newer alternative. Comparisons of these measures in other populations have demonstrated more favorable results for the MBT, although this has not been evaluated especially in people with MS. Objectives: To compare the BBS and the MBT ability to detect balance changes in ambulatory people with MS. Methods: 52 people with MS receiving outpatient physiotherapy were recruited. All had a primary diagnosis of MS and could ambulate indepen-dently with or without an assistive device. Each participant provided demographic details and a self-reported history of falls and near-falls, and completed the MBT, the 29-item Multiple Sclerosis Impact Scale (MSIS-29), the 12-item Multiple Sclerosis Walking Scale (MSWS-12), the BBS, the Modified Fatigue Impact Scale (MFIS), and the 6-Minute Walk test (6MW) before and after 8 weeks of routine physiotherapy. Results: The BBS and MBT respectively, had effect sizes (ES) of 0.37 and 0.70 and standard response mean values (SRM) of 0.74 and 1.52; statistically significant changes in BBS (−1.4 [1.9]; P = .01) and MBT (−5.31 [3.5]; P = .01) scores were demonstrated after treatment. 38% (n = 20) started with a baseline BBS maximum score of 56. No participant started with a baseline MBT maximum score of 28. The areas under the curve (AUC) for the MBT and BBS, respec-tively, were 0.88 (P > .01) and 0.77 (P = .01) for detecting mobility device use and 0.88 (P > .01) and 0.75 (P = .03) for self-report of near-falls. The MBT demonstrated higher correlation coefficients for each secondary measure than the BBS. Conclusions: The MBT demonstrated less ceiling effects and greater responsiveness and performed slightly better in detecting near-fallers and mobility aid users compared to the BBS. These findings suggest that the MBT may be a better outcome measure for detecting balance improvements in ambulatory people with MS.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Balance, Mini-BESTest, Berg Balance Scale

(RH27) EMPLOYMENT AND MULTIPLE SCLEROSIS: RECENT PERSPECTIVES FROM ADULTS WITH MSPhillip D. Rumrill,1 Richard T. Roessler,2 Malachy Bishop3

1Center for Disability Studies, Kent State University, Kent, OH; 2Rehabilitation Consultant, Fayetteville, AR; 3Rehabilitation Counseling, University of Kentucky, Lexington, OH

Background: Given their high levels of unemployment, people with multiple sclerosis (MS) can benefit from vocational rehabilitation interventions. Objectives: 1) To determine the demographic and disease predictors of employment. 2) To identify factors influencing job acquisition and retention. Methods: A random sample of 1924 adults with MS in nine National Multiple Sclerosis Society chapters provided demographic, illness, and employment concerns data.

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improve walking and balance performance in people with MS with mobility limitations. Future investigations should examine BWSTT in comparison to other treatment options in order to determine its effec-tiveness.

Supported by: National Multiple Sclerosis Society (IL Lot 006)Disclosure: Jacob J. Sosnoff, Douglas A. Wajda, Cherita Ousley, Jong Sung: Nothing to disclose. Lara A. Pilutti: National Multiple Sclerosis Society (grant/research support). Robert W. Motl: Biogen, Acorda (consulting fees, grant/research support); EMD Serono (fees for non-CME services from commercial interests or their agents).Keywords: Management of activities of daily living in MS, Rehabilitation

(RH30) THE EFFECTS OF PERICOOLING ON SIX-MINUTE WALK TEST PERFORMANCE IN PEOPLE WITH MULTIPLE SCLEROSISEsther Sosowsky, Meghan Burns, Elishiva Zinberg, Herbert I. Karpatkin

Physical Therapy, Hunter College, New York, NY

Background: People with MS (MS) are limited in their mobil-ity owing to thermosensitivity. Exercising at a sufficient volume and intensity to increase mobility can result in increased core tempera-tures and worsening of symptoms. The use of cooling garments to lower core temperature has been found to allow people with MS to exercise for longer periods. Previous studies have relied on cool-ing for an extended period prior to activity (precooling) to achieve improved exercise performance. Cooling during the performance itself, or pericooling, may allow for similar performance gains to be realized without spending the time needed for precooling. Objec-tives: The purpose of this study was to examine the effects of peri-cooling on 6-Minute Walk test (6MW) performance in people with MS. It was hypothesized that people with MS would have better 6MW performance while wearing a cooling vest as compared to an uncooled condition. If our hypothesis were correct, it would suggest that people with MS could achieve improved exercise performance without needing precooling. Methods: A randomized crossover design was used. Patients were randomized into cooled or uncooled conditions. Cooled subjects would perform a 6MW donning a com-mercially available cooling vest immediately prior to the walk. Walks would be performed once a week for 3 weeks. Total 6MW distance as well as minute-by-minute distance was recorded. Fatigue during the walk was measured using the Visual Analog Scale of Fatigue. Uncooled subjects would perform the identical protocol without a cooling device. Following the three walks in one condition, subjects would undergo a 2-week washout period and then repeat the same protocol in whatever condition they did not experience initially. Results: Six females (mean age, 51.33 years) with mild MS (mean Expanded Disability Status Scale [EDSS] score, 2.67) completed the study. A repeated-measures MANOVA showed that wearing the cooling vest resulted in walking significantly farther in the cooled condition (mean 1257.13 feet, SD 375.50) than in the uncooled condition (mean 1164.56 feet, SD 302.81); F1,17 = 4.63, P = .046. There were no significant differences in minute-by-minute walking dis-tances or in VAFS scores between the two conditions. Conclusions: The cooled condition resulted in significantly longer 6MW distances than did the uncooled condition in six females with mild MS. As most studies of cooling in MS utilize cooling prior to an exercise activity, these results indicate an alternative and less time-consuming means of achieving the beneficial effects of cooling.

Supported by: NoneDisclosure: Esther Sosowsky, Meghan Burns, Elishiva Zinberg: Nothing to dis-close. Herbert I. Karpatkin: Acorda Therapeutics (speakers’ bureau).Keywords: Thermosensitivity, Gait endurance

(RH31) THE EFFECTS OF YOGA AND MEDITATION ON WALKING, BALANCE, AND MOOD IN AMBULATORY MULTIPLE SCLEROSIS PATIENTSDarlene K. Stough,1 Mladen Golubic,2 Judi Bar,2 Jane Pernotto Ehrman,2 Daniel Musgrave,3 Francois Bethoux4

into account primary versus secondary causes, as well as the pres-ence of compensatory techniques. Treatment is a clinical decision-making process for respective limitations in ROM, strength, spasticity, and endurance addressed through correction, accommodation, and/or compensation. A correction of the problem is the first choice, but if this cannot be achieved, the problem can be accommodated through external devices, or compensated for through the utilization of neighboring muscle groups or altered functional techniques. Given the chronic and progressive nature of MS, it is important to note that an individual may be classified in more than one category and subsequently require multiple forms of treatment. Results: After per-forming the clinical pathway, the clinician should have a clear under-standing of the factor(s) causing footdrop, allowing individualized classification and intervention. Treatment-based classifications and clinical pathways are utilized throughout rehabilitation to help guide the clinician toward an effective treatment approach, and should be used in the case of footdrop in MS. Conclusions: Footdrop is a common problem in MS, which is frequently treated ineffectively, resulting in progression of disability that cannot be treated medically. It is hoped that by utilizing this clinical pathway clinicians can consis-tently develop individualized treatment plans.

Supported by: NoneDisclosure: Robert J. Schreyer, Emil Euaparadorn: Nothing to disclose. Herbert I. Karpatkin: Acorda Therapeutics (speakers’ bureau).Keywords: Comprehensive care and MS, Equipment in MS, Management of activities of daily living in MS

(RH29) BODY WEIGHT SUPPORTED TREADMILL TRAINING IN PEOPLE WITH MULTIPLE SCLEROSIS WITH MOBILITY LIMITATIONSJacob J. Sosnoff, Douglas A. Wajda, Lara A. Pilutti, Cherita Ousley, Jong Sung, Robert W. Motl


Background: Exercise has significant benefits for mobility in peo-ple with multiple sclerosis (MS). However, the benefits of exercise in people with MS with mobility impairments are not fully understood. A promising mode of exercise that is suited for individuals with mobility impairments is body weight supported treadmill training (BWSTT). However, there is a lack of data concerning BWSTT in this popula-tion. Objectives: To determine the effect of a 20-week BWSTT intervention on mobility, balance, and cardiorespiratory fitness in people with MS with walking impairment. Methods: 33 individu-als were enrolled in the investigation. 16 participants were assigned to the intervention arm and 17 to the control arm. The intervention arm consisted of 20 minutes of BWSTT twice a week for 20 weeks. The control arm received no treatment. Standardized assessments focusing on walking, balance, and cardiorespiratory fitness took place prior to the intervention, after 10 weeks of training, and at the end of the intervention. All outcome measures were placed into a 2 (condition: intervention/control) by 3 (time: pre, 10 weeks, and post) mixed-model analysis of variance (ANOVA). Results: Overall, the sample ranged in age from 25 to 64 years with a mean (SD) of 52.3 (8.6) years. Per design self-reported Expanded Disability Status Scale (EDSS) score ranged from 5.5 to 7.5 with a median of 6.5 (IQR 1.5). There was no difference between the control and intervention groups in age, gender, MS duration, and disability (P > .05 for all). Overall, a trend for an improvement in walking speed as a function of group and time was noted (F2,30 = 2.5; P = .11; η2 = 0.14). Sub-sequent analysis demonstrated that there was a 0.9-s increase (12%) in T25FW performance in the control arm, while there was a 6.8-s (30.9%) increase in the intervention arm. Statistical analysis of the BBS revealed a significant group by time interaction (F2,30 = 3.0; P = .05; η2 = 0.16). Post hoc analysis revealed that the control arm had a decrease in the BBS score of 4.7 points, while the experimental arm had an increase of 3.9 points. Overall, there was no effect of group or time on cardiorespiratory fitness as assessed by peak VO2 (P > .05). Conclusions: BWSTT is an efficacious approach to

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data by consulting key stakeholders. Methods: Two focus groups (FG) applying the nominal group technique were conducted in 2014, one in Europe (RIMS SIG Mobility meeting) and one in the United States (International Symposium on Gait & Balance in MS). The pur-pose of each FG was to identify and prioritize potential barriers and facilitators for sharing data with the proposed registry. FG data were analyzed individually and then combined through qualitative content analysis and quantitative combined ranking to produce a group sum-mary. A project-specific online questionnaire was written, based on the initial results of the combined FG analysis, to further explore bar-riers and facilitators from a broader professional audience invested in MS rehabilitation. Results: 21 individuals participated in the FGs, 12 in Europe and 9 in the United States. 66.7% were primar-ily engaged in research practice, and 76.2% worked primarily in MS. The combined FGs identified the following top 10 challenges and motivators related to sharing data: 1) database control and man-agement, 2) ethical and legal concerns, 3) data quality standards, 4) time, effort and cost for contributors and users, 5) clinical decision making and best practice, 6) data uniformity within the database, 7) sustainability, 8) comprehensive and deeper analysis, 9) collabora-tion, and 10) identifying research needs. The online questionnaire will be sent out in early 2015, gathering additional information on barriers, facilitators, potential needs, and solutions. Conclusions: These results will contribute to the decision-making process as to whether an international MS rehabilitation repository is feasible and the conditions under which key stakeholders would contribute. Addi-tional information: www.MsRehabRep.org

Supported by: Progressive MS AllianceDisclosure: Joanne M. Wagner: Acorda, Genzyme (consulting fees). Elissa Held Bradford, Ilse Baert: Nothing to disclose. Peter Feys: Biogen, Excemed, Novartis (consulting fees).Keywords: Repository

(RH33) CORRELATIONS BETWEEN PYRAMIDAL AND EXTRAPYRAMIDAL (BRAINSTEM, CEREBELLAR) FUNCTIONAL SYSTEM DISABILITY SCORES WITH MOBILITY AND STRENGTH PERFORMANCE IN MULTIPLE SCLEROSISSarah M. Ward,1 Hina Garg,2 Eduard Gappmaier2

1University of Utah, Salt Lake City, UT; 2Physical Therapy, University of Utah, Salt Lake City, UT

Background: Links between neurologic impairment and functional outcome measures are not well understood in multiple sclerosis (MS). Evaluation of sensitive, functional outcomes to measure disease progression and treatment efficacy besides neurologic disability is essential.Objectives: This study correlated and compared pyramidal and extrapyramidal (brainstem, cerebellar) Functional System (FS) scores with mobility and strength performance in ambulatory individuals with MS. Significant predictors of pyramidal and extrapyramidal scores were determined from mobility and strength measures. Meth-ods: Forty-six individuals with MS (36 females and 10 males, mean [range]: age [years], 54.4 [23–74]; Expanded Disability Status Scale [EDSS] score, 3.9 [3.0–5.5]; diagnosis duration [years], 15.3 [1–47]) and no concurrent relapses were recruited from the Universi-ty of Utah MS Rehabilitation and Wellness Clinic database. Mobility was assessed by Berg Balance Test (BBT), Timed Up and Go (TUG), Stair-climbing Test (ST), 6-Minute Walk test distance, 12-item Mul-tiple Sclerosis Walking Scale (MSWS-12), Activities-specific Balance Confidence (ABC), Multiple Sclerosis Functional Composite (MSFC; including 25-Foot Walk, 9-Hole Peg, and Paced Auditory Serial Addition tests). Strength was measured by dynamometers for Hand Grip (Left, Right; HG-L, HG-R) and Knee Extensors (Left, Right; KE-L, KE-R). Standardized neurologic assessment provided the pyramidal and extrapyramidal FS disability scores. Pearson correlations were calculated between pyramidal and extrapyramidal FS with mobil-ity and strength separately. Significant correlations (r > 0.35) were

1Neurological Institute–Mellen Center, Cleveland Clinic, Cleveland, OH; 2Center for Lifestyle Medicine, Cleveland Clinic, Cleveland, OH; 3Harmony Studios, Willoughby, OH; 4Department of Rehabilitation Services, Mellen Center, Cleveland Clinic, Cleveland, OH

Background: Yoga is one of the most frequently used complemen-tary therapies by patients with multiple sclerosis (MS). Both yoga and meditation were associated with positive effects on subjective well-being, but effects on physical function were less consistently demon-strated. We hypothesized that yoga, a form of exercise that involves breathing, relaxation/meditation, and postures, is more likely to influ-ence motor function (particularly walking and balance) than medita-tion alone. Objectives: To compare the effects of yoga and medita-tion with guided imagery on walking, balance, and psychological well-being in individuals with MS and walking limitations. Methods: Randomized parallel group trial comparing biweekly yoga practice (Yoga group) to meditative practice and walking guided imagery (Meditation group). All subjects participated in two 1-hour sessions per week for a total of 8 weeks, and were instructed to perform homework between sessions. Outcomes were measured at baseline (V1), shortly after the intervention (V2), and 4 weeks later (V3). Outcome measures included tests of walking (Timed 25-Foot Walk, 2-Minute Walk, spatiotemporal gait parameters), balance (Functional Reach Test, posturography), and self-report questionnaires of fatigue (Modified Fatigue Impact Scale), depression (Center for Epidemiolog-ic Studies Depression scale; CES-D), stress (Perceived Stress Scale-4; PSS-4), and walking limitations (12-item Multiple Sclerosis Walking Scale; MSWS-12). Results: 19 patients were enrolled, and 13 (7 Meditation and 6 Yoga) completed all visits; they had a mean (SD) age of 55 (6) years, 80% were women, the mean (SD) BMI was 26 (7), the mean (SD) symptom duration was 16 (10) years, and 30% walked with an assistive device. Subject characteristics were similar between groups at baseline, with the exception of variables reflecting gait disability (Yoga subjects were less disabled). There was a statisti-cally significant between-group difference in change scores between V1 and V2 for PSS-4 (P = .0033) and CES-D (P = .031), favoring the Yoga group. No significant between-group difference was observed for the other variables. Both interventions were well tolerated, and all participants found their allocated intervention beneficial. Con-clusions: Compared to meditation, yoga practice led to greater improvement of anxiety and depression symptoms in patients with MS and walking limitations, but there was no difference in measures of walking and balance. Further research is needed to better under-stand the potential benefits of yoga and meditation in MS.

Supported by: CMSCDisclosure: Darlene K. Stough, Mladen Golubic, Judi Bar, Jane Pernotto Ehrman, Daniel Musgrave: Nothing to disclose. Francois Bethoux: Acorda Thera-peutics (consulting fees, grant/research support); Concert Pharmaceuticals, Gen-zyme, IMPAX Pharmaceuticals (consulting fees); Merz Pharma (grant/research support).Keywords: Complementary/alternative therapies in MS, Comprehensive care and MS, Rehabilitation and MS

(RH32) PERCEIVED BARRIERS AND FACILITATORS FOR SHARING DATA WITH AN INTERNATIONAL MULTIPLE SCLEROSIS REHABILITATION REPOSITORYJoanne M. Wagner,1 Elissa Held Bradford,1 Ilse Baert,2 Peter Feys2

1Department of Physical Therapy and Athletic Training, Saint Louis University, St. Louis, MO; 2REVAL/BIOMED, Hasselt University, Diepenbeek, Belgium

Background: The Progressive Multiple Sclerosis Alliance (PMSA) funded an infrastructure award entitled “Towards a Shared Data Repository to Enhance the Standards of Rehabilitation in MS: Feasi-bility and Capacity Building.” This project prepares the development of an international MS rehabilitation repository infrastructure to retro-spectively assemble databases describing and investigating effects of different rehabilitation interventions and measures, and to prospec-tively stimulate MS centers, researchers, and clinicians to collect and share data with uniform outcome measures for specific research ques-tions. Objectives: To identify barriers and facilitators for sharing

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Posters: Symptom Management

of specialized training for therapists and students on patient out-comes, and compare student competencies to those of students in the regular curriculum.

Supported by: National Multiple Sclerosis Society, Greater Carolinas ChapterDisclosure: Nothing to discloseKeywords: Education

SYMPTOM MANAGEMENT

(SX07) REVIEW OF PAIN MANAGEMENT IN MULTIPLE SCLEROSISJoseph I. Asemota

Harvard School of Public Health, Boston, MA; General Pediatrics, Boston Children’s Hospital, Boston, MA

Background: Pain, a common symptom estimated to affect as many as 65% of multiple sclerosis (MS) patients, can be debilitating and significantly impair function and overall quality of life (QOL). Characterizing pain syndromes in MS is challenging, and may be dichotomized based on origin into central neuropathic pain (CNP) and nociceptive pain (NP). Despite the significant impact on patients’ QOL, pain is often overlooked and undertreated. Also, treatment options for pain in MS are not well delineated, making its management a challenge. Objectives: To review current treatment modalities for MS-related pain. Methods: A literature search was done using PubMed. Relevant articles were reviewed and significant findings synthesized. Results: Conventional analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, the most commonly used medications in pain management protocols, are not efficacious for MS pain. Common first-line agents in managing MS-induced CNP include tricyclic antidepressants, serotonin-norepi-nephrine reuptake inhibitors, topical lignocaine, and calcium channel α2-δ subunit ligands. These drugs disrupt pain impulse transmission, but their side effects limit use. The use of drug combinations may reduce side effects, improve tolerability, and enhance compliance. Carbamazepine is the most effective agent for treatment of trigeminal neuralgia in MS. Again, its side effects are problematic. When com-bined with gabapentin, the dose can be reduced, and this improves tolerability. Nociceptive pain is managed using antispastics, muscle relaxants, benzodiazepines, and anticonvulsants. Spasticity, a com-mon cause of NP in MS, is effectively managed with antispastics such as baclofen, tizanidine, and gabapentin administered orally. Refrac-tive cases may require invasive therapies like intrathecal baclofen or botulinum toxin. Generally, antispastic agents have few disturbing side effects, although high doses may result in muscle weakness. Recently, the cannabinoid nabiximols has demonstrated efficacy in long-term symptomatic management of MS spasticity. Ancillary treat-ment options for MS-related pain include physical therapy, transcu-taneous electrical nerve stimulation, and acupuncture. Acupuncture is hypothesized to act via release of endorphin and serotonin, the body’s natural painkillers, in CNS pain pathways. Current manage-ment guidelines recommend individualization of therapy for MS-related pain. Conclusions: Adequate treatment of MS-related pain is important. Clinicians need to be acquainted with the various thera-pies to enable them to identify optimal therapy for individual patients.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Complementary/alternative therapies in MS, Comprehensive care and MS, Pain management

(SX08) WITHDRAWN

(SX09) GENDER DIFFERENCES IN MULTIPLE SCLEROSIS–RELATED PAIN, CORRELATION WITH BURDEN OF DISEASEMirla Avila,1 Volker Neugebauer,2 John DeToledo1

1Neurology, Texas Tech, Lubbock, TX; 2Pharmacology and Neuroscience, Texas Tech, Lubbock, TX

used to predict pyramidal and extrapyramidal FS scores. SPSS 20.0 was used for statistical analysis. Results: Pyramidal FS was signifi-cantly (P < .05) correlated with KE-R (r = −0.343), KE-L (r = −0.313), MSFC (r = −0.424); brainstem FS with MSWS (r = 0.404), TUG (r = 0.401), ABC (r = −0.397), ST (r = 0.412); and cerebellar FS with BBT (r = −0.607), HG-R (r = 0.343), TUG (r = 0.380), MSWS-12 (r = 0.433), ABC (r = −0.319), and MSFC (r = −0.404). In the combined model of MSFC and KE, ST and BBT were found to be sig-nificant predictors of pyramidal and brainstem and cerebellar scores, respectively. Conclusions: Strong correlations between extrapyrami-dal FS and mobility scores suggest that performance on mobility tests (ST, BBT) provides more information about brainstem and cerebellar tract involvement in individuals with MS. Correlations between pyra-midal FS and KE strength and MSFC indicate that these measures are more informative of pyramidal tract involvement in MS. These quick, quantitative measures of mobility and strength may prove to be useful for MS management and clinical research.

Supported by: NoneDisclosure: Sarah M. Ward, Hina Garg: Nothing to disclose. Eduard Gapp-maier: Acorda Therapeutics (consulting fees, speakers’ bureau); National Multiple Sclerosis Society (grant/research support).Keywords: Comprehensive care and MS, Epidemiology of MS, Neurologic dis-ability

(RH34) MULTIPLE SCLEROSIS EDUCATION TRACK IMPROVES SELF-RATED COMPETENCIES IN PHYSICAL THERAPY STUDENTSPrudence Plummer,1 Angela Rosenberg,1 Alexis A. Williams,1 Corinne J. Bohling,1 Heather L. Eustis,1 Joseph Miller,1 Diane Meyer,2 Kaye Gooch,3 Lisa Johnston1

1Allied Health Sciences, The University of North Carolina, Chapel Hill, NC; 2Center for Rehabilitation Care, UNC Healthcare, Chapel Hill, NC; 3National Multiple Sclerosis Society, Greater Carolinas Chapter, Raleigh, NC

Background: The Multiple Sclerosis Standardized Training and Education Program with University Partners (MS STEP UP), a partner-ship between the University of North Carolina (UNC) Division of Physical Therapy and the Greater Carolinas Chapter of the National Multiple Sclerosis Society, is a program to educate and mentor physi-cal therapy students to become MS-Certified Specialists (MSCS) after graduation. Objectives: This study evaluated the outcomes of the first five cohorts of students to complete MS STEP UP. Methods: Students applied for selection to MS STEP UP in their first year of the DPT program at UNC. The 2-year educational track, conducted concurrently with the second and third year of the DPT curriculum, included didactic instruction, clinical experiences, and service activi-ties. Scholars were also encouraged to tailor class assignments and capstone projects to focus on MS-related topics. Volunteer clinical experiences allowed the students to observe MS-specialized physical therapists and neurologists and other health-care providers. Scholars regularly participated in community-based activities including Nation-al Multiple Sclerosis Society events, board meetings, fundraisers, and self-help groups. The primary outcome used to evaluate the educa-tional track was the MS Competencies Rating Scale (MSCRS), which was completed by each scholar before they started MS STEP UP and at the end of the first and second years. Activities of the scholars were also recorded quarterly in an online database. Results: Since 2008, 10 DPT students have completed the MS STEP UP program. Four of the first six scholars have obtained MSCS certification. MSCRS data showed significant increases in self-rated MS competen-cies across the 2 years. The number of competency items on which the scholars rated their knowledge as “above average” or “excel-lent” increased significantly (P < .001) from a mean (±SD) of 0.13 ± 0.35 items (0%) at baseline to 23.3 ± 3.8 items (53%) after the first year, and 41.0 ± 3.1 items (93%) after the second year. Conclu-sions: MS STEP UP improves the clinical skills and knowledge of DPT students, as demonstrated by self-rated competencies. Moreover, the program appears to adequately prepare graduates to become certified specialists in MS. Future research should evaluate the effects

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patients who used myPTM for spasticity or pain between January 1, 2013, and April 15, 2014. Methods: Charts were reviewed from the electronic medical record (UTSW EPIC) for patients utilizing the myPTM during the time mentioned and then statistically analyzed for any trends that elucidated satisfaction with implementation of the myPTM device and relief of spasticity. Results: In this descrip-tive case series, 15 subjects, all with a simple continuous infusion mode with only baclofen, were tracked. We measured the number of patient activations of myPTM per day: the mean (SD) was 3.62 (0.43), and the median was 3.62. The mean number of successful activations was 17.5; unsuccessful activations, 2.5; and lockout attempts, 1.5. Patient satisfaction was not measured regularly in all subjects. Conclusions: We concluded that we need better outcome measurements for patient satisfaction with this device, and a way to measure satisfaction on a more frequent basis than medical visits. Further, it would probably be more useful to quantify the improve-ment (the difference in pain and function before and after myPTM) of spasticity to delineate patient satisfaction as opposed to using anecdotal accounts from the patient. In addition, it would be ideal to study a larger number of patients in order to make claims representa-tive of a wider population. However, we note that patients were able to activate the device successfully the majority of the time, with few lockouts.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Complementary/alternative therapies in MS, Comprehensive care and MS, Management of activities of daily living in MS

(SX11) PILOT STUDY OF A TOPICAL ADHESIVE CONTAINING ANESTHETIC AND HEATING COMPONENTS TO REDUCE INJECTION PAIN WITH SUBCUTANEOUS MULTIPLE SCLEROSIS MEDICATIONSTheodore R. Brown, Virginia I. Simnad

MS Center at Evergreen Health, Evergreen Health, Kirkland, WA

Background: Injection pain and fear of pain (“needle phobia”) are common problems that limit adherence to injection of subcutane-ous (SC) medications for treating multiple sclerosis (MS). Relieving injection-site pain may improve the tolerability of MS medica-tions. SYNERA is a peel-and-stick topical adhesive (S-TA) with a novel heating component designed to enhance the delivery of an anesthetic mixture of lidocaine and tetracaine. This adhesive is approved in the United States for use in dermal analgesia for venous access and superficial dermatologic procedures and may be useful in reducing MS drug injection pain and needle phobia. Objectives: To determine the effect of S-TA on immediate pain following injec-tion and other measures of comfort with SC MS drug injection and to determine the preferred period of application (30 to 60 minutes) prior to injection. Methods: Thirty subjects with MS taking SC interferon beta (IFNβ) or glatiramer acetate (GA) and having injec-tion pain rated 3 or higher on a visual analog scale (VAS) of 0 to 10 are being enrolled in an open-label prospective study. Subjects will complete injection diaries. S-TA is applied prior to drug injection, initially for 60 minutes and subsequently for 30 minutes, to assess differences based on time of application. The study duration is 3 to 6 weeks (1–2 weeks of baseline observation followed by 2–4 weeks of on-drug observation), depending on which MS drug product the subject is taking. The primary outcome measure is immediate pain upon injection (0–10 VAS). Secondary measures will include fear of injection, 12- and 24-hour ratings of pain by VAS, and 24-hour local injection site reaction scale (LISR) score. Statistical analysis (t test or equivalent nonparametric method) will assess mean values on and off study drug and for comparing 30- versus 60-minute applica-tions. Results: Thirty subjects were enrolled in the study: 4 in the IFNβ group and 26 in the GA group. The average age was 52.9 years, average Expanded Disability Status Scale (EDSS) score was 3.9, and percent female was 87%. Average baseline ratings for pain on the 0–10 VAS were 5.8 (immediate), 2.9 (12-hour), and 2.2 (24-hour); baseline fear of injection was 4.0 (0–10 VAS),

Background: Multiple sclerosis (MS) is a demyelinating disorder characterized by inflammation of the central nervous system that is more predominant in women. Pain occurs in 29% to 86% of MS patients, and its management may be challenging. Central pain is estimated to occur in 17% to 52% of patients with MS. MS pain may present as burning, aching, pricking, stabbing, or squeezing. Painful extremity spasms are also classed as central pain. About 32% of MS patients complain of pain among their most severe symptoms. Severe pain invariably interferes with the MS patients’ quality of life, as it is a frequent, disabling, and incompletely controlled symptom. There is preliminary evidence that the progression of pain symptoms to the state of chronic severe pain is the result of neurochemical and func-tional changes in the central nervous system. Studies of patients with chronic pain syndromes (non-MS patients), utilizing structural mag-netic resonance imaging (MRI) and magnetic resonance spectros-copy (MRS), reveal abnormalities in brain regions involved in pain processing, including the thalamus, amygdala, prefrontal cortex, cingulate, and somatosensory cortex. Previous studies have shown gender differences in the prevalence of chronic pain only for selected pain conditions. Although MS is more common in women and pain is a common and disabling symptom in these patients, no studies have looked at whether the incidence, clinical features, and severity of pain are different in women versus men with MS. Objectives: Evaluate possible gender differences in MS-related pain. To assess for any relation with MS-related pain and the burden of disease (number and localization of T2 white-matter lesions in brain MRI and the presence of spinal cord involvement). Methods: This is an ongo-ing questionnaire-based prospective study. The estimated number of MS patients is 80 to 100. The modified McGill questionnaire will be used for the patient to self-rate pain severity. Demographic informa-tion is obtained from medical records. The presence of neuropathic pain, somatic or visceral pain, and different qualitative and quantita-tive aspects of pain will be documented. Brain MRI will be evaluated for the presence of and number of hyperintense lesions in T2 and presence or absence of spinal cord involvement. MRI scans are per-formed on a 1.5-T MRI scanner. FLAIR and T2-weighted images will be evaluated for the presence of lesions, in particular for lesions in the thalamus, amygdala, prefrontal cortex, cingulate, and somato-sensory cortex. Results: This is an ongoing study, and the results are pending. Conclusions: In this study we will evaluate the possible gender differences in MS-related pain and will evaluate if there is any relation with MS-related pain and the burden of disease.

Supported by: Laura Bush funding researchDisclosure: Mirla Avila: Laura Bush (grant/research support). Volker Neuge-bauer, John DeToledo: Nothing to disclose.Keywords: Complementary/alternative therapies in MS, Comprehensive care and MS

(SX10) EFFECTIVENESS OF MEDTRONIC INTRATHECAL DRUG DELIVERY PUMP PERSONAL THERAPY MANAGER IN SPASTICITY MANAGEMENTLukmon Babajide

Physical Medicine and Rehabilitation, UT Southwestern Medical Center, Dallas, TX

Background: Intrathecal drug delivery pumps are used as an interventional device for spasticity management for patients with neurologic disorders. The purpose of this research is to determine efficiency and patient satisfaction with the myPTM device, which has been used successfully for pain management. The outcomes from this study could lead to improved efficiency of spasticity management by physician and patient. The benefits of patient-controlled management of spasticity through the myPTM device are numerous. It could reduce pain, improve range of motion, positioning, and function, and lead to a sense of greater patient involvement in care. Further, observation of the utilization of the pump may aid in physician-controlled dosing that provides better relief for the patient while maintaining adequate muscle function. Objectives: It is hypothesized that the institution of the myPTM pump will reduce periodic spasticity and increase patient satisfaction. A retrograde study was conducted in order to reveal efficacy of the myPTM pump in select patients. The study includes

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Supported by: NoneDisclosure: Adam D. Comer: Nothing to disclose. David H. Mattson: Acorda Therapeutics, Biogen Idec, Genzyme, Novartis, Teva Neuroscience (fees for non-CME services from commercial interests or their agents, grant/research support); Actelion, ONO, Roche (grant/research support); Bayer, EMD Serono, Pfizer, Questcorp (fees for non-CME services from commercial interests or their agents).Keywords: Comprehensive care and MS, Management of activities of daily living in MS

(SX13) IMPACT OF NURSING INTERVENTIONS ON REDUCING ADVERSE EVENTS RELATED TO TECFIDERALisa Laing, Carrie L. Sammarco, Judith Minitti, Cara Desanctis

MS Comprehensive Care Center, NYU Langone Medical Center, New York, NY

Background: Oral dimethyl fumarate (DMF) is approved in the United States for the treatment of relapsing forms of multiple sclero-sis (MS). In the phase 3 DEFINE and CONFIRM studies, the most common adverse events associated with DMF included flushing and gastrointestinal (GI) events. For most patients, these events were mild or moderate in severity and decreased in incidence after the first month of treatment. In clinical practice, DMF-associated adverse events have been largely related to medication tolerability rather than serious safety concerns. Tolerability of a medication may affect adherence, which in turn may affect efficacy of the drug. However, tolerability-related adverse events of DMF can often be overcome with time. If adverse events due to tolerability are not managed early, appropriate patients may discontinue therapy prematurely. Objec-tives: To investigate the impact of a structured nursing initiation protocol (IP) on DMF adverse effects and adherence. Methods: We are providing detailed written instructions and measure toler-ability and adherence in a real-world population anticipating that setting expectations early will have beneficial effects compared to what has been seen in other practices and as compared to the clini-cal trial experience. Additionally, we believe that even patients who have a difficult initial experience taking Tecfidera, once on therapy and having overcome tolerability issues, are very happy with their experience on the drug. A measure of patient satisfaction at this point in time will quantify this experience. Patients are sent home with a “Tecfidera Patient Information Sheet,” a “Food Suggestion List,” and a “Tecfidera Weekly Diary” that tracks whether they took their medication with food and what mitigation strategies they took (aspirin, Pepto-Bismol, or other OTC medication), and whether or not they have flushing, diarrhea, nausea, vomiting, headache, rash, or other symptoms. Measures are taken daily. In addition, our clinical practice utilizes an alternate titration schedule of 120 mg once a day for weeks 1 and 2, followed by 240 mg once a day for weeks 3 and 4, followed by 240 mg twice a day. Results: To date 30 patients (N = 50) have been enrolled, and 18 have started medication using this protocol. Preliminary results show that both GI and flushing side effects appear to be mitigated using the NYU Titration Protocol for Tecfidera. There have been no discontinuations to date. Conclu-sions: The NYU Nursing Titration Protocol for Tecfidera appears to mitigate tolerability-related side effects, thus resulting in patient adher-ence. The study will be completed by March 2015, at which time we will have final results.

Supported by: Biogen IdecDisclosure: Lisa Laing, Carrie L. Sammarco: Biogen Idec (consulting fees, grant/research support). Judith Minitti, Cara Desanctis: Nothing to disclose.Keywords: Disease-modifying treatments in MS, Nursing management in MS

(SX14) COMORBIDITY IS ASSOCIATED WITH PAIN IN MULTIPLE SCLEROSISKirsten M. Fiest,1 John D. Fisk,2 Scott B. Patten,3 Helen Tremlett,4 Christina Wolfson,5 Sharon Warren,6 Kyla McKay,4 Lindsay Berrigan,7 Ruth Ann Marrie8

1Internal Medicine, University of Manitoba, Winnipeg, MB, Canada; 2Psychiatry, Dalhousie University, Halifax, NS, Canada; 3Community Health Sciences and Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; 4University of British Columbia, Vancouver, BC, Canada; 5McGill University, Montreal, QC, Canada; 6University of Alberta, Edmonton, AB, Canada; 7Dalhousie University, Halifax, NS, Canada; 8Medicine, University of Manitoba, Winnipeg, MB, Canada

and baseline LISR score was 2.9 (0–6 scale). Two treatment-related adverse events were recorded: muscle spasm and lightheadedness (n = 1, subject withdrew) and mild dermatitis (n = 1, completed). Con-clusions: Final results will be presented at the CMSC meeting, including pain and fear of injection ratings, analyses of 60- versus 30-minute applications, and global impressions. This study explores the clinical utility of a topical adhesive containing anesthetic and heating components in managing subcutaneous medication injections used for MS treatment.

Supported by: Galen PharmaceuticalsDisclosure: Theodore R. Brown: Acorda, Biogen, EMD Serono, Genzyme, Nuvo Research, Teva (consulting fees); Acorda, Biogen, Genzyme, Pfizer, Teva (fees for non-CME services from commercial interests or their agents); Astellas, Biogen Idec, Galen, Teva (grant/research support). Virginia I. Simnad: Actelion, Biogen Idec, Teva Neuroscience (grant/research support); Biogen Idec (consulting fees).Keywords: Comprehensive care and MS, Nursing management in MS, Psycho-logical issues and MS

(SX12) EFFECT OF DALFAMPRIDINE ON SUBJECTIVE DOMAINS OF FUNCTIONING IN PATIENTS WITH MULTIPLE SCLEROSISAdam D. Comer, David H. Mattson

Neurology, Indiana University School of Medicine, Indianapolis, IN

Background: Dalfampridine is an FDA-approved medication to improve walking speed in patients with multiple sclerosis (MS). Initial studies indicate that some patients can be classified as respond-ers. Responders are defined by an initial walking speed of 8 to 45 seconds and ≥20% improvement in walking speed on dalfampridine. Based on this definition, studies suggest that 25% to 33% of patients are responders. In addition to improvements in walking speed, some studies suggest that there may be other benefits in patient functioning that are not easily quantifiable. Objectives: To determine whether dalfampridine treatment in patients with MS provides benefit in subjective domains of functioning in patients who are not classified as responders in a Timed 25-Foot Walk (T25FW). Methods: IRB approval was requested and granted to perform a retrospective chart review of all individuals started on dalfampridine between March 2009 and September 2011 at an academic institution in order to determine: 1) objective improvement of walk time; and 2) participants’ subjective improvements in functioning. Individuals’ walk times were recorded at both baseline and follow-up subsequent to starting treatment with dalfampridine. During follow-up appointments, responses on perceived benefit were classified into the categories of stability, stamina, speed, strength, upper-extremity functioning, transfers, or other, in order to determine whether the individual subjectively felt an improvement in functioning while taking dalfam-pridine. Demographic information such as duration of MS diagnosis, length of time on dalfampridine, and Expanded Disability Status Scale (EDSS) score were also extracted from participant charts. Results: Of the 92 participants who met inclusion criteria, 15 of 56 (26.8%) who had an initial walking speed of 8 to 45 seconds had ≥20% improvement in walking speed at follow-up. Additionally, 3 of 12 individuals with an initial walking speed faster than 8 seconds and 1 of 5 individuals with an initial walking speed slower than 45 seconds also improved by ≥20%. Furthermore, 3 individuals who did not walk initially were able to walk at follow-up. None of 15 (0%) walking speed responders subjectively felt they responded in other domains of functioning. 21 of 73 (28.8%) ambulatory participants felt they responded most prominently in domains of functioning including stamina and stability. 9 of 19 (47.4%) nonambulatory participants felt they responded most prominently in domains of func-tioning including stamina, stability, and upper-extremity functioning. Conclusions: In a retrospective chart review of 92 individuals started on dalfampridine, 26.8% met the traditional definition of a responder, which is similar to prior studies estimating a 25% to 33% response rate. There may also be a subset of patients who have a subjective response to dalfampridine, and additional studies should focus on evaluating these individuals.

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To identify PSG-documented first night sleep abnormalities related to SL and REM-L in a large cohort of patients with MS who report fatigue. Methods: Retrospective analysis of patients with MS who reported fatigue and underwent overnight PSG studies. Results: 206 patients with MS who reported fatigue completed overnight PSG. Analysis of SL in these patients identified <30 minutes in 102/207 (49%), >30 minutes in 105/207 (51%), and >60 minutes in 52/207 (25%). No REM sleep was identified in 25/206 (12%) of these patients. In those patients who reached REM sleep, 115/181 (63%) had REM-L >110 minutes, and 63/181 (35%) had REM-L >180 minutes. Of those patients who achieved REM sleep, normal % REM sleep range was identified in 67/180 (37%); 105/180 (58%) had <17% total REM sleep; and 50/180 (28%) had <10% total REM sleep. Conclusions: Fatigue is common in patients with MS. Sleep disorders are common in patients with MS with fatigue. Prolonged SL and REM-L are common in MS patients and can result in reduced overall sleep time and REM sleep time; thus, they may directly contribute to daytime fatigue in these patients.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Comprehensive care and MS, Fatigue

(SX16) MULTIPLE SCLEROSIS AND SLEEP DISORDERS: EXPLORATION OF SLEEP-DISORDERED BREATHING–APNEA HYPOPNEA INDEX IN NON-REM VERSUS REM SLEEP IN MULTIPLE SCLEROSISMark Gudesblatt,1 Steven Xian,1 Barbara Bumstead,1 Myassar Zarif,1 Smitha Thotam,1 Lori Fafard,1 Konstantina Bardhi,1 Marijean Buhse2

1South Shore Neurologic Associates, Patchogue, NY; 2School of Nursing, State University of New York at Stony Brook, Stony Brook, NY

Background: Fatigue is a common and often disabling symp-tom reported in patients with multiple sclerosis (MS). Fatigue as a symptom likely reflects the culmination of a complex heterogeneous problem reported as a simple complaint. Improved understand-ing of some pathogenic aspects contributing to fatigue may lead to improved treatment efficacy and satisfaction. Sleep-disordered breathing (SDB) is a common cause of daytime fatigue and impaired quality of life. Characterization of the types and degrees of SDB in patients with MS has not been well explored in a large cohort. Analysis underlying sleep architecture disturbances and SDB in non-REM and REM sleep in this population is very limited. Objectives: To explore the correlation of polysomnography (PSG)–documented first night sleep abnormalities related to SDB and determine differ-ences in SDB between non-REM and REM sleep in a large cohort of MS patients who report fatigue. Methods: Retrospective analysis of MS patients who reported fatigue and underwent overnight PSG studies. Results: 206 patients with MS who reported fatigue underwent overnight PSG. Of these patients, 64/206 (31%) had no significant SDB (AHI < 4.9), 79/206 (38%) exhibited mild SDB (5 < AHI < 19.9), 39/206 (19%) moderate SDB (20 < AHI < 39.9), and 24/206 (12%) severe SDB (AHI > 40). PSG analysis of SDB during non-REM sleep revealed that 81/205 (40%) had no SDB (AHI < 4.9), 70/205 (34%) mild SDB (5 < AHI < 19.9), 36/205 (18%) moderate SDB (20 < AHI < 39.9), and 18/205 (9%) severe SDB (AHI > 40). In contrast, PSG analysis of SDB during REM sleep of those patients who reached REM sleep (12% did not achieve REM sleep) demonstrated that 61/181 (34%) had no SDB (AHI < 4.9), 50/181 (28%) mild SDB (5 < AHI < 19.9), 38/181 (21%) moder-ate SDB (20 < AHI < 39.9), and 32/181 (18%) severe SDB (AHI > 40). Conclusions: Fatigue is common in patients with MS. Sleep disorders are common in patients with MS who report fatigue. SDB during REM sleep may be common and more severe than non-REM SDB in patients with MS who report fatigue. Awareness of the differ-ences in degree of SDB between non-REM- and REM-associated sleep might affect the consequences of this problem and reinforce the need for treatment even if the percentage of REM sleep is limited during the sleep study.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Comprehensive care and MS, Fatigue

Background: Comorbidities can affect the diagnosis and man-agement of multiple sclerosis (MS) and reduce quality of life. The high prevalence of pain in MS is established, but little is known about how comorbidities influence these symptoms. Objectives: To examine the relationship between comorbidity and pain in MS. Methods: From July 2010 to March 2011 we recruited consecutive patients with definite MS from four Canadian MS clinics. Participants completed the Health Utilities Index (HUI-Mark III) and a validated comorbidity questionnaire at three visits over 2 years. The HUI’s 5-point utility-weighted pain scale was initially dichotomized into two clinically relevant groups: those with and without pain that disrupts normal activities. We used logistic regression to assess the associa-tion of pain with each comorbidity individually at baseline (as odds ratios [OR], with 95% confidence intervals [95% CI]), and over time. Secondly, changes in pain scores (5-point ordinal scale) between vis-its were modeled using a logistic model with generalized estimating equations (GEE) to better determine longitudinal within-person effects of comorbidity on pain. All models were adjusted for age, sex, time since symptom onset, disability (Expanded Disability Status Scale [EDSS] score), and the presence of other comorbidities. Results: Of 949 participants, most were female (75.2%) and white (85.4%), with a mean (SD) age of 48.6 (11.4) years and a relapsing-remitting course (72.4%). At baseline, 41.5% of participants had at least one comorbid health condition, and the prevalence of disruptive pain was 40.5%. The incidence of disruptive pain at years 1 and 2 were 12.1 and 12.7 per 100 persons, respectively. Significant base-line population-level effects on pain of peripheral vascular disease, fibromyalgia, rheumatoid arthritis, IBS, IBD, migraine, COPD, depres-sion, anxiety, hypertension, and high cholesterol persisted at all time points (P < .006). Significant individual-level effects on the presence of worsening pain were seen for bipolar disorder (OR, 3.05; 95% CI, 1.32-7.05), lupus (OR, 2.82; 95% CI, 1.26-6.29), COPD (OR, 1.50; 95% CI, 1.08-2.09), anxiety (OR, 1.49; 95% CI, 1.07-2.08), and autoimmune thyroid disease (OR, 1.40; 95% CI, 1.00-1.97). Conclusions: Pain is a concern for all individuals with MS, but more so for those with comorbidities. Closer examination of these associations may provide guidance for better management of these potentially disabling symptoms in people with MS.

Supported by: CIHR, Rx&D Health Research FoundationDisclosure: Kirsten M. Fiest, John D. Fisk, Scott B. Patten, Helen Tremlett, Christina Wolfson, Sharon Warren, Kyla McKay, Lindsay Berrigan: Nothing to disclose. Ruth Ann Marrie: Sanofi-Aventis (conduct of clinical trial).Keywords: Epidemiology of MS

(SX15) MULTIPLE SCLEROSIS AND SLEEP DISORDERS: EXPLORATION OF SLEEP LATENCY AND REM SLEEP LATENCY IN A COMMUNITY COHORT OF PATIENTS WITH MULTIPLE SCLEROSIS WHO REPORT FATIGUEMark Gudesblatt,1 Steven Xian,1 Barbara Bumstead,1 Myassar Zarif,1 Smitha Thotam,1 Lori Fafard,1 Marijean Buhse,2 Konstantina Bardhi11South Shore Neurologic Associates, Patchogue, NY; 2School of Nursing, State University of New York at Stony Brook, Stony Brook, NY

Background: Fatigue is a common and often disabling symptom reported in patients with multiple sclerosis (MS). Fatigue likely reflects a complex heterogeneous disorder even if reported as a monodi-mensional complaint. More effective understanding of underlying aspects contributing to the pathogenesis of fatigue reported might lead to improved treatment efficacy and patient satisfaction. Patients with MS also frequently report insomnia. The time to sleep onset is patient-reported and thus can be unreliable. Analysis of time to sleep onset by polysomnography (PSG) in MS patients reporting fatigue is not well characterized. Sleep latency (SL) is defined as the time from getting into bed to sleep onset. A normal SL is defined as <30 minutes. REM latency (REM-L) is defined as time from sleep onset to REM sleep. A normal REM-L is defined as 80 to 110 minutes. The normal range for REM sleep is defined as 17% to 28% of total sleep per night. The longer it takes to get to sleep, the less time one has to sleep at night. The longer it takes to get to REM sleep, the less time there is for REM sleep. Reduction of both total night sleep and REM sleep may affect daytime fatigue, mood, and cognition. Objectives:

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ic and clinical characteristics, physical activity, exercise self-efficacy, function, social support, exercise outcome expectations, and exer-cise goal setting and planning. The data were analyzed using path analysis in Mplus. Results: The social-cognitive model provided a good fit for the data (comparative fit index [CFI] = 0.996, standard-ized root-mean-square residual [SRMR] = 0.020). Self-efficacy (β = 0.16), function (β = 0.22), goal-setting (β = 0.15), and planning (β = 0.19) had statistically significant direct effects on physical activity. Self-efficacy further had an indirect effect via function (β = 0.12). This model explained 27% of variance in physical activity behavior. Conclusions: Researchers should consider self-efficacy, function, goal-setting, and planning as targets when designing behavioral interventions for increasing physical activity among African Ameri-cans with MS.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Complementary/alternative therapies in MS, Epidemiology of MS, Management of activities of daily living in MS

(SX19) PHYSICAL ACTIVITY AND EXERCISE TRAINING IN MULTIPLE SCLEROSIS: A QUALITY REVIEW AND CONTENT ANALYSIS OF PERCEIVED DETERMINANTS AND CONSEQUENCESYvonne C. Learmonth, Robert W. Motl


Background: There is a corpus of quantitative research that has been systematically summarized documenting the determinants and consequences of physical activity and exercise training in people with multiple sclerosis (MS). The existing qualitative research has not been systematically reviewed, but such an endeavor is critical for establishing the breadth and importance of determinants and consequences of physical activity and exercise that are based on the views of MS patients. Objectives: We adopted methodology based on theoretical frameworks for undertaking a systematic review and content analysis of qualitative research examining determinants and consequences of physical activity and exercise participation in MS. Methods: Electronic databases and article reference lists were searched to identify qualitative studies of exercise and physical activ-ity in MS. Content analysis of the determinants and consequences of physical activity and exercise was undertaken using an inductive analysis guided by the Physical Activity for people with Disabilities (PAD) framework and Social Cognitive Theory (SCT), respectively. Results: We reviewed 19 articles. The determinants of physical activity and exercise included environmental (eg, minimal profes-sional support) and personal (eg, fatigue) barriers as well as envi-ronmental (eg, peer support) and personal (eg, self-management) facilitators. The most common presumably modifiable barriers and facilitators were social exclusion and peer support, respectively. The consequences of physical activity and exercise included adverse physical (eg, increased fatigue) and self-evaluative (eg, loss of con-trol) outcomes as well as benefits in physical (eg, maintenance of physical function), social (eg, increased participation in social activi-ties), and self-evaluative (eg, self-management and control) outcomes. Of the consequences, self-management and control was the most common benefit reported by people with MS. Conclusions: Such results will inform future quantitative research on the determinants and consequences of physical activity and exercise in those with MS and can be adopted for developing clinical recommendations and interventions for physical activity and exercise in MS.

Supported by: NoneDisclosure: Yvonne C. Learmonth: National Multiple Sclerosis Society (MB029) (grant/research support). Robert W. Motl: Biogen, Acorda (consulting fees, grant/research support); EMD Serono (fees for non-CME services from commercial inter-ests or their agents).Keywords: Comprehensive care and MS, Management of activities of daily living in MS, Physical activity and exercise in MS

(SX17) “WAITING FOR THE SCIENCE TO CATCH UP WITH THE PRACTICE”: A MORE CAUTIOUS TREND IN SOCIAL MEDIA DISCUSSIONS OF CCSVI TREATMENT FOR MULTIPLE SCLEROSISSinéad M. Hynes,1 Susan Forwell,1 Setareh Ghahari21Department of Occupational Science and Occupational Therapy, University of British Columbia, Vancouver, BC, Canada; 2Occupational Therapy, Queens University, Kingston, ON, Canada

Background: Previous research, carried out at this laboratory, showed that many people—both patients and health professionals—advocated for angioplasty treatment for symptom control in multiple sclerosis (MS). From analyzing videos uploaded to YouTube.com between October 2009 and July 2011, it was found that 86% of participants reported improvements in function following treatment for chronic cerebrospinal venous insufficiency (CCSVI). Objectives: To determine if these participants were still reporting benefits of the treat-ment, if a new cohort of participants are using social media to report on CCSVI treatment, and if perspectives on CCSVI have changed in recent years. Methods: There were two stages of data collec-tion: a) follow-up search for videos (after July 2011) on participants identified in the previous study’s dataset (group 1), and b) videos uploaded by new participants between August 2011 and Decem-ber 2014 (group 2). Videos were included if they were related to MS and CCSVI, were in English, and involved a person with MS. Conference proceedings and promotional videos were excluded. The videos were analyzed using a predefined code book. Results: Group 1: Of the 1789 videos from the previous study, 621 videos were uploaded by 293 people with MS. From these, 106 people with MS uploaded between 1 and 197 new videos since July 2011, of which 30 videos (one video per participant) talk about the impact of treatment for CCSVI and were included. Group 2: A new search of videos related to CCSVI (August 2011 to December 2014) pro-vided 651 new uploads. Only 20 videos met the inclusion criteria. Combining the groups and comparing with the previous study, there is an 89.34% decrease in the number of new CCSVI videos being uploaded per month (1.25 videos/month since July 2011 vs. 13.32 videos/month prior to July 2011). Participants’ expectations of the treatment have changed; the longer-term results have been disap-pointing, with some now happy to “wait for the science to catch up with the practice.” Some continue to report on the benefits, especially in the short term, but there is an air of caution now surrounding the so-called “liberation therapy.” Conclusions: Social media indicate a shift in the volume and messages about CCSVI and its treatment. As increased experience about CCSVI treatment has not yielded the expected results, practitioners who may be faced with pressure to provide unproven treatments in the future should be understanding but evidence-driven when supporting therapies for MS.

Supported by: NoneDisclosure: Nothing to discloseKeywords: Complementary/alternative therapies in MS, Social media trends

(SX18) SOCIAL-COGNITIVE DETERMINANTS OF PHYSICAL ACTIVITY IN AFRICAN AMERICANS WITH MULTIPLE SCLEROSISDominique L. Kinnett-Hopkins,1 Robert W. Motl21Kinesiology, University of Illinois at Urbana-Champaign, Champaign, IL; 2Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL

Background: Epidemiology conveys that multiple sclerosis (MS) is more prevalent in whites than in African Americans. However, African Americans may experience a more aggressive MS disease course than their white counterparts, thereby greatly influencing phys-ical activity levels in African Americans with MS. This underscores the importance of identifying theoretical determinants of physical activity that can inform the design of behavioral interventions among African Americans with MS. Objectives: This study examined variables from social-cognitive theory as determinants of physical activity in African Americans with MS. Methods: 151 African Americans with MS were recruited through the NARCOMS registry and completed a battery of questionnaires, which included information on demograph-

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2014). However, little is known about co-occurring symptoms associ-ated with tobacco use in people with MS. Objectives: The primary aim of this study was to identify symptoms and symptom groups asso-ciated with smoking behaviors in people with relapsing-remitting MS (RRMS). Methods: A cross-sectional, descriptive study of people with RRMS was used. Measures included a subset of the 2010 Behavioral Risk Factor Surveillance System (BRFSS) survey tobacco questions, the MS-Related Symptom Scale (MS-RS), revised version, and the Self-Report Expanded Disability Status Scale (SR-EDSS). Tobacco questions covered use ever, frequency, and quantity of use. Analysis used descriptive statistics, factor analysis to identify symptom groupings, and linear regression models. Results: The convenience sample comprised 101 participants with RRMS, who averaged 43 years old. The majority were female (83%), white (86%), and mar-ried (64%). A majority (52%) were ever smokers. The overall mean duration of MS disease and score on the SR-EDSS in ever smokers were 8.5 years and 3.5, respectively. Ever smokers were more likely to be single compared to never smokers (38% vs. 20%, P = .03). Controlling for race and age, two symptom groups of co-occurring symptoms were identified according to smoking status: 1) ever smok-ers had higher scores on the Mental/Emotional factor (symptoms: loneliness, depression, and anxiety) (P < .04); and 2) regular, but not current, smokers had higher scores on the heat intolerance/vision factor (heat intolerance, co-occurring heat intolerance/vision, blurred vision, and double vision) (P < .03). Conclusions: The cur-rent study is a first step in understanding the relationship between smoking behavior, MS symptom groupings, and disease course in people with MS. Understanding the association between symptoms and tobacco use can improve management of MS through targeted person-centered care. These findings can also increase the success of tobacco-cessation efforts with resulting reduction in health-care costs and improved quality of life.

Disclosure: Nothing to discloseKeywords: Epidemiology of MS, Management of activities of daily living in MS

(SX22) SLEEP PROBLEMS AND SYMPTOM CORRELATES IN PEOPLE WITH MULTIPLE SCLEROSIS: A PILOT STUDYPamela K. Newland


Background: Sleep problems are common in people with multiple sclerosis (MS). According to a recent study, sleepiness can manifest with other symptoms, especially in different subgroups of people with MS (Newland et al., 2014). However, the day-to-day associations between sleep and symptoms of fatigue and pain remain unclear and warrant further investigation (Pokryszko-Dragan et al., 2013). Objectives: To compare the prospective relationships between sleep and other symptoms of MS, including fatigue, depression, pain, frequent urination, and demographic characteristics in people with MS. Methods: The Pittsburgh Sleep Quality Index (PSQI) col-lected sleep information at baseline, and the Self-report Expanded Disability Status Scale (SR-EDSS) measured disability. The MS-Related Symptom Scale (MS-RS) was sent via emailed electronic diary (ED) messages to a link from Redcap data capture to people with MS for 7 consecutive days over a 2-week period. Results: Data from EDs were collected from 28 people with MS from an MS clinic and the community. The majority (83%) were female, with mean age of 42 years and SR-EDSS score of 3.7. The mean global PSQI score was 7.9. There were significant differences observed for sleep problems with younger age (r = −0.250, P =. 04) and higher SR-EDSS score (r = 0.544, P = .04). Furthermore, there were significant associa-tions between sleep problems and pain (P < .0001), depression (P = .009), frequent urination (P < .0001), and fatigue (P = .003). Data were analyzed using SAS 9.4. Conclusions: Sleep problems are a frequent complaint among people with MS. Our preliminary data suggest that sleep problems are associated with greater disability. Interventions are needed to target the specific sleep issues in people

(SX20) EFFECTS OF DALFAMPRIDINE EXTENDED RELEASE ON MOTOR FUNCTION IN PEOPLE WITH MULTIPLE SCLEROSIS AFTER 18 MONTHSAlbert C. Lo,1,2 Jennifer A. Ruiz,1 Kayla M. Olson,1 Elizabeth W. Triche1,3

1Mandell Center for Multiple Sclerosis, Mount Sinai Rehabilitation Hospital, Hartford, CT; 2Departments of Neurology and Engineering, Brown University, Providence, RI; 3Department of Epidemiology, Brown University School of Public Health, Providence, RI

Background: Motor improvements have been reported in people with multiple sclerosis (MS) on dalfampridine extended release (D-ER). However, little evidence exists on the longer-term benefits of taking D-ER across a range of motor functions. Objectives: Assess motor function in people with MS on D-ER for 18 months. Methods: Prior to initiating D-ER, 52 participants enrolled in this prospective observational study of people with MS prescribed 10 mg D-ER per usual care; 33 were observed for 18 months. The following outcomes were assessed at baseline (pre D-ER) and follow-up (18 months): Timed 25-Foot Walk (T25FW), 6-Minute Walk (6MW), Six Spot Step Test (SSST), 12-Item Multiple Sclerosis Walking Scale (MSWS-12), 9-Hole Peg Test (9HPT), and Box and Block Test (BBT). Changes from baseline to 18 months were assessed separately for 1) those remaining on D-ER at 18 months (n = 18) and 2) those who discontinued D-ER (n = 15) prior to 18 months, using the Wilcoxon signed rank test. Results: Among those who remained on D-ER, the following significant improvements (median change, P value) were seen at 18 months compared to baseline (pre D-ER): SSST domi-nant (dom) (−3.0, .006), SSST combined (−2.3, .056), MSWS-12 (−11.5, .050), BBT dom (2.8, .023), and BBT non-dom (3.8, .006). Among those who discontinued D-ER (n = 15), only SSST dom (−2.0, .020) was improved. No significant improvements were seen in the following among those who remained on D-ER: T25FW (−0.3, .196), 6MW (3.0, 0.776), SSST non-dom (−0.9, .278), 9HPT dom (−1.1, 0.122), and 9HPT non-dom (−1.3, .064). Among those who discon-tinued D-ER, no improvements were found for T25FW (−0.1, .820), 6MW (−6.0, .096), SSST non-dom (−0.8, .776), SSST combined (−2.0, .191), MSWS-12 (−2.1, .670), 9HPT dom (0.7, .443), 9HPT non-dom (−3.2, .460), BBT dom (−0.8, .953), and BBT non-dom (−0.5, .239). Conclusions: Current findings suggest improvements in gross motor function, dynamic gait, and self-perceived walking for people with MS on D-ER sustained after 18 months are possible. Additional research including an untreated comparison group is needed to better understand the longer-term effects of D-ER on motor function in people with MS.

Supported by: Acorda, Mt. Sinai Rehabilitation HospitalDisclosure: Albert C. Lo: Acorda, National Multiple Sclerosis Society, VA (grant/research support); Acorda, National Multiple Sclerosis Society (advisory board); Consortium of Multiple Sclerosis Centers (honorarium); National Mul-tiple Sclerosis Society, Consortium of Multiple Sclerosis Centers (travel reimburse-ment). Jennifer A. Ruiz, Kayla M. Olson: National Multiple Sclerosis Society, Acorda (grant/research support). Elizabeth W. Triche: Mt. Sinai Rehabilitation Hospital, rEVO Pharmaceuticals (consulting fees); Mt Sinai Rehabilitation Hos-pital (travel reimbursement); National Institutes of Health, National Multiple Sclerosis Society, Acorda (grant/research support).Keywords: Comprehensive care and MS, Management of activities of daily living in MS, Symptom management

(SX21) SYMPTOM GROUPS ASSOCIATED WITH SMOKING AMONG PEOPLE WITH RELAPSING-REMITTING MULTIPLE SCLEROSISPamela K. Newland


Background: Evaluation of the magnitude of the effect of cigarette smoking on the severity of multiple sclerosis (MS) may help to deter-mine underlying disease mechanisms and is important, as studies have reported a high percentage of smoking in people with MS (Marrie et al., 2009). Studies also suggest that tobacco use increases the likelihood of developing MS and is a possible risk factor for increased disease severity and progression (Manouchehrinia et al.,

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(SX24) QUALITATIVE FINDINGS FROM A PILOT RANDOMIZED CONTROLLED TRIAL OF A BRIEF MULTIDISCIPLINARY CONSULTATION INTERVENTION FOR TREATING SEXUAL DYSFUNCTION IN MULTIPLE SCLEROSISLaura C. Schairer,1 Elana Mendelowitz,1 Sara Flood,1 Jason Botvinick,1 Jessica H. Sloan,1 Elizabeth S. Gromisch,1 Stacey Snyder,1 Helen Quinn,1 Lisa Glukhovsky,1 Gabriel Hoffnung,1 Frederick W. Foley2

1Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY; 2Holy Name Medical Center, Teaneck, NJ

Background: Sexual dysfunction (SD) in individuals with multiple sclerosis (MS) is a common yet often untreated symptom. Objec-tives: The aim of the study was to conduct a pilot randomized con-trolled trial of a brief two-visit multidisciplinary behavioral interven-tion utilizing a consultation model for adults with MS and SD. It was hypothesized that the intervention group would be more likely to sub-jectively report significant improvements compared with the control group in sexual functioning and relationship satisfaction. Methods: Participants were recruited from the MS Center at Holy Name Medi-cal Center. There are a total of 49 participants, with 23 randomized to the intervention condition and 26 to the control condition. Those in the control condition received educational materials on the topic of sexuality and intimacy in MS. Those in the intervention condition received two consultation intervention sessions along with their sexual partner, each separated by 1 month to allow for completion of prac-tice assignments between sessions. At the end of the study, partici-pants were asked the following question: “Overall, did you find that participating in this study was helpful, neutral, or detrimental to your sex life with your partner?” Additionally, participants were asked an open-ended question about aspects of the intervention or educational materials that they found helpful. The responses to this open-ended question were qualitatively scored. Results: Of the 49 people who completed the study, 36 people stated that participating in the study was helpful, 13 said it was neutral, and 0 thought it was detrimental to their sex lives. Of the 23 participants in the intervention condition, 20 responded “helpful” (87%) and 3 responded “neutral” (13%). Of the 26 participants in the control condition, 16 responded “helpful” (61%) and 10 responded “neutral” (39%). A Pearson chi-square test was performed to examine the relation between randomization group and subjective results. People in the intervention group were more likely to report that the study was “helpful” than the control group: χ2

1 = 4.05, P = .044. The odds of finding the study “helpful” were 4.16 times higher if in the intervention group than in the control group. Conclusions: Behavioral and educational interventions have the potential to improve sexual functioning and sexual satisfaction for people living with MS.

Supported by: CMSC

Disclosure: Laura C. Schairer, Elana Mendelowitz, Sara Flood, Jason Botv-inick, Jessica H. Sloan, Elizabeth S. Gromisch, Stacey Snyder, Helen Quinn, Lisa Glukhovsky, Gabriel Hoffnung: Nothing to disclose. Frederick W. Foley: Bayer (consulting fees).

Keywords: Comprehensive care and MS, MS and the caregiver/family, Psycho-logical issues and MS

with MS. These results support investigation of the longitudinal course of sleep and associated changes in symptoms in this population.


Keywords: Management of activities of daily living in MS, Symptom manage-ment

(SX23) TRANSFORMING LIVES: EVALUATION OF IMMEDIATE AND 6-MONTH OUTCOMES FROM THE CAN DO PROGRAM, CAN DO MULTIPLE SCLEROSISLauri O’Brien,1 Sara Anne Tompkins1,2

1Programs, Can Do Multiple Sclerosis, Avon, CO; 2Program Planning and Evaluation Consulting, Madipen, LLC, Fort Collins, CO

Background: The CAN DO Program offers the most comprehen-sive view of multiple sclerosis (MS), taking participants on a profound exploration of their unique condition and empowering them to live fully with MS. Objectives: Using an interdisciplinary team, this intensive 4-day experience goes beyond traditional programs by providing comprehensive assessments and education about MS—its effects, treatment options, and lifestyle adaptation strategies. The indi-vidualized course of MS calls for more empowering and person-spe-cific interventions, as optimism can affect MS by promoting physical adjustment and healthy coping strategies and predicts positive physi-cal health outcomes (de Ridder, 2000; Rasmussen, 2009). The CAN DO Program’s health-focused orientation is supported by research indicating that exercise improves quality of life and certain MS symp-toms (eg, Motl & McAuley, 2009; Jensen et al., 2012). Methods: The current study evaluated combined data from pre, post, and 6-month follow-ups (3 programs, 2012–2014; people with MS and SP). The baseline sample consists of 119 participants (51% people with MS) with a mean age of 50.56 years and length of diagnosis of 10.84 years; there were 104 at post and 88 at 6 months. Results: Paired-sample t tests found that people with MS reported a significant increase in MS Symptom Management Self-efficacy (MSSE) (t38 = 6.27, P < .05) from pre (mean 523.59, SD 132.62) to 6 months (mean 664.87, SD 130.97); improved MS Specific Benefit Finding (BFiMSS) (t37 = 4.02, P < .05) from pre (mean 90.59, SD 18.08) to 6 months (mean 100, SD 15.78); and increase in couple illness communication (CICS) (P < .05). Additional outcomes include sig-nificant increase in MS Caregiver Benefit Finding (BFiMSCare) (P < .05); achievement of short-term goals, positive attitude, and behavior changes at 6 months. Conclusions: The CAN DO Program is a per-sonal and powerful MS program increasing confidence to transform challenges into possibilities. CAN DO produced outcomes of benefit finding, confidence in MS management, and illness communication at 6 months. Improved benefit finding is related to meaning-based coping strategies with direct effects on life satisfaction (Pakenham, 2006), thus demonstrating the mission of addressing multiple areas to help people live more fully with MS. Implications of increasing positive constructs include better medication adherence, less morbid-ity, and increased longevity in healthy and chronically ill populations (eg, Cuffee et al., 2012; Moskowitz et al., 2008). The CAN DO Program is an effective way to create empowerment and assist in multiple aspects of an individual’s MS journey.

Supported by: Can Do MSDisclosure: Nothing to discloseKeywords: Management of activities of daily living in MS, MS and the care-giver/family, Quality of life with MS

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WHITAKER RESEARCH TRACK

The late Dr. John N. Whitaker was a world-famous research-er in multiple sclerosis. His work inspired many scientists to enter the field of MS and develop their skills and talents. Each year, the Consortium of Multiple Sclerosis Centers (CMSC) honors Dr. Whitaker’s memory by presenting one award for innovative research by a young investigator. This year the CMSC and the Foundation of the CMSC will present a prize to a scholar whose work exemplifies the mission of this vision-ary leader in multiple sclerosis.

CAPITALIZING ON THE INTERACTION BETWEEN PATIENTS AND HEALTH-CARE PROVIDERS: A QUALITATIVE STUDY TO EXPLORE THE EXERCISE-PROMOTION NEEDS AND WANTS OF MULTIPLE SCLEROSIS PATIENTSYvonne C. Learmonth,1 Brynn C. Adamson,1 Julia M. Balto,1 Chung-yi Chiu,1 Isabel Molina-Guzmán,2 Marcia Finlayson,3 Barry J. Riskin,1 Robert W. Motl1

1Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL; 2Department of Latina/Latino Studies, University of Illinois at Urbana-Champaign, Urbana, IL; 3School of Rehabilitation Therapy, Queens University, Kingston, ON, Canada

Background: There is increasing recognition of the benefits and safety of exercise and its centrality in the coordinated care of people with multiple sclerosis (MS) who have mild-to-moderate disability. Substantial evidence indicates that people with MS are not engag-ing in sufficient amounts of physical activity and exercise for health benefits. There is growing recognition that the interaction between patients and providers is an important opportunity to promote physi-cal activity and exercise in MS. To capitalize on this opportunity, we need to understand the wants and needs of patients regarding the promotion of exercise during interactions with providers. Objec-tives: We adopted a basic qualitative research design and explored the needs and wants of those with mild-to-moderate MS regarding advice and support for exercise from health-care providers. Meth-ods: Participants were identified using purposive sampling and recruited from the midwestern United States. Of the 50 people who underwent screening, 40 volunteered who had an Expanded Dis-ability Status Scale (EDSS) score ≤5.5 and who ranged from physi-cally inactive through regular exercisers. Those people underwent a semistructured, scripted interview for capturing the wants, needs, and desires for promotion of physical activity and exercise through providers. Three researchers performed coding and thematic analysis of the transcribed interviews, and this was supplemented by member-checking and journal data. Results: Spiral analysis of the data identified main themes regarding the wants and needs of patients for the promotion of exercise through providers. Patients reported a) the expectation that providers can and will promote exercise; b) needing provider support regarding information on benefits, risks, and safety of exercise; c) needing information that facilitates continued behavior change such as community resources and support groups; and d) needing ongoing monitoring, updates, and encouragement by the provider. Conclusions: Health-care providers may be the most important messengers of physical activity and exercise information to those with MS. Subsequent research should query providers about the needs, wants, and resources for promoting physical activity and exercise among patients with MS.

Supported by: National Multiple Sclerosis Society (IL0017) Disclosure: Yvonne C. Learmonth: National Multiple Sclerosis Society (MB029) (grant/research support). Brynn C. Adamson, Julia M. Balto, Chung-yi Chiu, Isabel Molina-Guzmán, Marcia Finlayson, Barry J. Riskin: Nothing to disclose. Robert W. Motl: Biogen, Acorda (consulting fees, grant/research support); EMD Serono (fees for non-CME services from commercial interests or their agents). Keywords: Complementary/alternative therapies in MS, Management of activi-ties of daily living in MS, Physical activity and exercise in MS

PEAK TURNING VELOCITY AS A MARKER OF BALANCE CONFIDENCE AND WALKING LIMITATION IN PEOPLE WITH MULTIPLE SCLEROSISGautam Adusumilli,1 Samantha Lancia,1 Victoria A. Levasseur,2 Robert T. Naismith,1 Joanne M. Wagner3

1Department of Neurology, Division of Neuroimmunology, School of Medicine, Washington University in St. Louis, St. Louis, MO; 2School of Medicine, University of Missouri, Columbia, MO; 3Department of Physical Therapy and Athletic Training, Saint Louis University, St. Louis, MO

Background: Straight-line gait parameters have been used exten-sively in people with multiple sclerosis (MS) to assess balance and walking limitations. Turn parameters have not yet been used and may provide additional information for these assessments. Objec-tives: Determine whether peak turning velocity (PTV) during the 6-Minute Walk test (6MW) and Timed Up and Go (TUG) adds pre-dictive power to straight-line stride velocity (SV) in the modeling of self-perceived balance confidence and walking limitation in people with MS. Methods: 91 subjects (Expanded Disability Status Scale [EDSS] scores 0–6.5) performed the TUG and 6MW. Spatiotemporal gait analysis was conducted using APDM Opal wireless body-worn sensors, which include a gyroscope, accelerometer, and magnetom-eter. Six sensors were placed on the subject: two on the ankles, two on the wrists, one on the lumbar spine region, and one on the thorax. Stepwise regression analyses were conducted independently for the TUG and 6MW to determine addition of PTV to SV in the prediction of balance confidence (Activities-specific Balance Confidence Scale; ABC) and walking limitation (12-item Multiple Sclerosis Walking Scale; MSWS-12). Results: 6MW SV and 6MW PTV were mod-erately correlated (r = 0.527; P < .0001). TUG SV and TUG PTV were moderately correlated (r = 0.576; P < .0001). Whereas SV during the 6MW predicted 20.2% of ABC, the addition of 6MW PTV increased the predictability of the model to 32.8% (P < .0001). SV during the TUG predicted 18.5% of ABC, but the addition of TUG PTV increased the model’s predictability to 28.1% (P < .001). Similar results were found for the MSWS-12, as SV during the 6MW predicted 27.9% of ABC, but increased to 40.5% with the addition of 6MW PTV (P < .0001). SV during the TUG predicted 26.9% of MSWS-12, but the addition of TUG PTV increased the model to 35.9% (P < .001). Conclusions: Turning velocity appears to improve modeling of self-perceived balance confidence and walking limitations when added to a straight-line gait parameter. Consistent results were found whether using a test consisting of a single turn (TUG) or multiple turns (6MW). This emphasizes that turn speed and stability should be assessed clinically, and quantitative measures of turning may have potential as an outcome measure for clinical trials.

Supported by: None Disclosure: Gautam Adusumilli, Samantha Lancia, Victoria A. Levasseur: Nothing to disclose. Robert T. Naismith: Acorda, Bayer, Biogen, Genzyme, Novartis, Questcor (consulting fees). Joanne M. Wagner: Acorda, Genzyme (con-sulting fees).

Keywords: Clinical measures, Equipment in MS

EVALUATING CEREBELLAR CONTRIBUTIONS TO PHYSICAL PERFORMANCE AND COGNITION IN MULTIPLE SCLEROSISNora E. Fritz,1,2 Chuyang Ye,3 Jerry Prince,3,4 Zhen Yang,3 Jennifer Keller,1 Allen Jiang,1 Chen Chun Chiang,1 Rhul Marasigan,1 Peter A. Calabresi,5 Kathleen M. Zackowski1,2,5

1Motion Analysis Laboratory, Kennedy Krieger Institute, Baltimore, MD; 2Physical Medicine and Rehabilitation, Johns Hopkins School of Medicine, Baltimore, MD; 3Electrical Engineering, Johns Hopkins University, Baltimore, MD; 4Computer Engineering, Johns Hopkins University, Baltimore, MD; 5Neurology, Johns Hopkins University, Baltimore, MD

Background: Individuals with multiple sclerosis (MS) demonstrate motor (ie, strength and walking) and cognitive deficits. The cerebel-lum plays an important role in both motor and cognitive processing, and is a common site for MS-related disability. Objectives: The objective of this study was to examine the relationship of motor and cognitive performance to cerebellar lobule and peduncle volumes and diffusivity measures in individuals with MS. Methods: Twenty-

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nine individuals with relapsing-remitting MS (mean ± SD age: 50.0 ± 11.3 years; symptom duration: 12.8 ± 9.9 years; 18 females; median [range] Expanded Disability Status Scale [EDSS] score: 4.0 [1–6.5]) and 23 age- and gender-matched controls (age: 51.9 ± 11.0 years; 15 females) volunteered for this study. All individuals participated in a clinical assessment and 3-T brain magnetic reso-nance imaging (MRI) including diffusion tensor imaging (fractional anisotropy [FA] and mean diffusivity [MD] only), MPRAGE and FLAIR sequences. We segmented the cerebellar lobules and peduncles and compared individuals with MS to controls using t tests. We used cor-relation analyses to understand the relationship of the cerebellum to clinical measures. Results: Diffusivity (FA: P = .029; MD: P = .002) of the superior cerebellar peduncle (SCP), the primary cerebellar output, was significantly worse in individuals with MS compared with controls. However, the cerebellar lobule volumes, peduncle volumes, and diffusivity of the middle and inferior cerebellar peduncles in individuals with MS were not different from in controls. Increased volume of the motor lobules (I–V, VIII) was significantly associated with increased strength (r = 0.37; P = .007), faster walking speed (r = 0.30; P = .032), and better performance on the Timed 25-Foot Walk (T25FW) (r = −0.34; P = .019), but was not related to sensory performance (r = −0.23; P = .108). Increased volume of the cogni-tive lobules (VI–VII) was associated with better performance on the Symbol Digit Modalities Test (r = 0.36; P = .009). Increased dif-fusivity in the SCP was significantly associated with reduced falls in the past month (r = −0.37; P = .007), increased walking speed (r = −0.28; P = .041), and better performance on the T25FW (r = 0.28; P = .042). Conclusions: These data show that cerebellar volumetric and white-matter connections are selectively associated with physi-cal performance and cognition in individuals with MS. Examining structure-function relationships improves our understanding of indi-vidualized differences in this heterogeneous group and may provide an avenue for targeted rehabilitation.

Supported by: National Multiple Sclerosis Society

Disclosure: Nora E. Fritz, Chuyang Ye, Zhen Yang, Jennifer Keller, Allen Jiang, Chen Chun Chiang, Rhul Marasigan: Nothing to disclose. Jerry Prince: Diagnosoft, Inc (consulting fees, ownership interest). Peter A. Calabresi: AbbVie, Prothena, Vaccinex, Vertex (consulting fees); Biogen Idec, MedImmune, National Multiple Sclerosis Society, Novartis (grant/research support). Kathleen M. Zack-owski: Biogen Idec, National Multiple Sclerosis Society (grant/research support).

Keywords: Cerebellum, Imaging and MS

DETERMINING RELIABLE CHANGE USING THE ABBREVIATED MODIFIED FATIGUE IMPACT SCALERyan E. Allen,1 Jared M. Bruce,1 Amanda Bruce,2,3 Abigail R. Ness,1 Morgan B. Glusman,1 Joan M. Thelen,1 Sharon G. Lynch4

1Psychology, University of Missouri–Kansas City, Kansas City, MO; 2Pediatrics, University of Kansas Medical Center, Kansas City, KS; 3Children’s Mercy Hospital, Kansas City, MO; 4Neurology, University of Kansas Medical Center, Kansas City, KS

Background: Up to 90% of patients with multiple sclerosis (MS) report significant and debilitating fatigue. Treatment of fatigue often includes the prescription of stimulants, exercise, and/or psy-chotherapy. Despite this multimodal treatment approach, clinicians working with MS patients do not have a quick and reliable means of accurately determining change in a patient’s fatigue. Objectives: The aim of this study was to evaluate the psychometric properties of a brief fatigue scale and calculate clinically useful reliable change scores. Methods: Fifty-nine relapsing-remitting MS patients com-pleted the modified Fatigue Impact Scale-5 (MFIS-5) at baseline and at 10-week follow-up as part of a larger study examining treatment adherence. Test-retest reliability of baseline and 10-week composite scores was assessed using a single-measure, two-way, random-effects analysis of variance intraclass correlation (sICC) with absolute agreement. Reliable change scores at the 0.80 and 0.90 confidence intervals were calculated using the Jacobson and Truax reliable change formula. Results: The MFIS-5 demonstrated good test-retest reliability (sICC = 0.75). Reliable change calculations indicated that 4-point differences on the MFIS-5 represent meaningful change at the 0.80 confidence interval. Differences of 6 points represent change at the 0.90 confidence interval. Conclusions: Despite widespread fatigue in MS, no brief measures have been shown to reliably detect clinically meaningful change. Results provide evidence that the MFIS-5 can be used to reliably evaluate significant change in MS patients’ fatigue. Changes of ≥4 on the abbreviated fatigue measure represent a reliable and meaningful change. The MFIS-5 may be given at baseline and after treatment to evaluate fatigue outcomes as part of empirically supported treatment protocols.

Supported by: None Disclosure: Ryan E. Allen, Amanda Bruce, Abigail R. Ness, Morgan B. Glus-man, Joan M. Thelen: Nothing to disclose. Jared M. Bruce: Novartis (consulting fees, speakers’ bureau, fees for non-CME services from commercial interests or their agents). Sharon G. Lynch: Biogen Idec, Teva, MedImmune, Chugai, Alexion, Novartis, Genzyme, Roche, Acorda, Actelion, Opexa (grant/research support). Keywords: Comprehensive care and MS, Fatigue

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(DX68) PREDICTIVE VALUE OF MRI MEASURES IN PATIENTS WITH RELAPSING MULTIPLE SCLEROSIS RECEIVING IFNß-1A SUBCUTANEOUSLY THREE TIMES WEEKLY OR IFNß-1A INTRAMUSCULARLY ONCE WEEKLY: POST HOC ANALYSES OF EVIDENCE DATAAnthony T. Reder,1 Mark S. Freedman,2 Fernando Dangond,3 Juanzhi Fang,3 Patricia K. Coyle4 1University of Chicago, Chicago, IL; 2University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada; 3EMD Serono, Inc., Rockland, MA; 4Department of Neurology, Stony Brook University Medical Center, Stony Brook, NY

Background: In EVIDENCE, patients with relapsing multiple scle-rosis were randomly assigned to interferon beta-1a (IFNβ-1a) 44 µg subcutaneously (SC) three times weekly (tiw; n = 339) or IFNβ-1a 30 µg intramuscularly (IM) once weekly (qw; n = 338). Objectives: Examine the predictive value of early magnetic resonance imag-ing lesions for achieving no evidence of disease activity (NEDA) at week 48 (no relapses or confirmed 12-week disability worsening [≥1 point Expanded Disability Status Scale increase] by week 48, and no T2 lesions newly occurring or enlarging from weeks 24 to 48) in patients treated with IFNβ-1a. Methods: T2 and pre-/post-contrast T1 scans were performed at screening, study day 1, and every 4 weeks through week 24, with another T2 scan at week 48. Post hoc analysis assessed predictive values of early lesions for future NEDA status. Results: By week 8, mean gadolinium-enhancing (Gd+) lesions/patient/scan (including all scans up to that point) were 0.79 with IFNβ-1a SC tiw versus 1.34 with IFNβ-1a IM qw (P = .002); mean new/enlarging T2 lesions/patient/scan were 0.42 versus 0.55, respectively, by week 12 (P = .008). Differences remained significant at subsequent monthly time points up to the final monthly scan at week 24. At week 48, more patients receiving IFNβ-1a SC tiw versus IFNβ-1a IM qw met NEDA status (44% vs. 32%, respec-tively; P = .003). Of those without baseline (BL) Gd+ lesions, 81 of

150 and 61 of 143 IFNβ-1a SC tiw and IFNβ-1a IM qw patients, respectively, achieved week 48 NEDA (negative predictive value [NPV] 54.0% and 42.7%); 41 of 129 and 31 of 134 with BL Gd+ lesions in these groups achieved week 48 NEDA (31.8% and 23.1%). Of those without week 8 Gd+ lesions, 109 of 220 and 74 of 192 IFNβ-1a SC tiw and IFNβ-1a IM qw patients, respectively, achieved week 48 NEDA (NPV 49.5% and 38.5%); 16 of 71 and 19 of 100 with week 8 Gd+ lesions in these groups achieved week 48 NEDA (22.5% and 19.0%). Similar predictive value was seen for week 8 T2 lesions. 56.8% and 44.5% of IFNβ-1a SC tiw and IFNβ-1a IM qw groups, respectively, with no BL or week 8 Gd+ lesions had week 48 NEDA, as did 37.0% and 29.1% with Gd+ lesions at BL but not week 8. Conclusions: IFNβ-1a 44 µg SC tiw patients had significantly fewer lesions versus IFNβ-1a 30 µg IM qw by early in treatment and higher likelihood of week 48 NEDA status. BL/week 8 lesions predicted future disease activity, but patients receiving IFNβ-1a 44 µg SC tiw were more likely to achieve week 48 NEDA status with or without early lesions.

Supported by: EMD Serono, Inc., Rockland, MA, USA (a subsidiary of Merck KGaA, Darmstadt, Germany); Pfizer Inc., New York, NY, USA

Disclosure: Anthony T. Reder: Acorda, Bayer, Biogen, Genzyme, Novartis, Questcor, Pfizer, Sanofi, Serono, Teva (consulting fees). Mark S. Freedman: Bayer HealthCare (grant/research support); Novartis, Teva Canada Innova-tion, Sanofi-Aventis, Bayer HealthCare, Biogen Idec, EMD Serono (Canada), Genzyme, Opexa (personal compensation). Fernando Dangond, Juanzhi Fang: EMD Serono, Inc., Rockland, MA, USA, a subsidiary of Merck KGaA, Darm-stadt, Germany (employee). Patricia K. Coyle: Accordant, Acorda, Bayer, Biogen, Genentech/Roche, Genzyme/Sanofi, Mylan, Novartis, Serono, Teva (consulting fees); Actelion, Genzyme/Sanofi, Novartis, Opexa (grant/research support).

Keywords: Disease-modifying treatments in MS, Imaging and MS, Interferon beta

ADDENDUM[Editor’s Note: The following abstract should have been included in the section

“Posters: Disease Management, Mechanisms, and Treatment.”]

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Author Index

AAbourjaily, Heather .................................57Adamson, Brynn C. ................................85Adamson, Meagan .....................................4Adusumilli, Gautam ................................85Afsari, Nasima .........................................34Agrella, Stephanie ....................................57Akinwuntan, Abiodun E. ....................3, 62Alexander, Katharine ...............................33Allen, Ryan E. .........................................86Almalik, Yaser ..........................................33Alschuler, Kevin ................................23, 33Alvarez, Enrique ......................................30Ambalavanan, Poornima .........................34Amblee, Vaishak A. .................................28Amburgey, Justin M. .................................6Amezcua, Lilyana ................................2, 67Amjad, Faria S. ........................................34Amtmann, Dagmar .................................23Anderson, Rebecca M................................1Andre, Carolyn J. St. ...............................27Aparicio, Jose ......................................2, 67Aradi, Stephen .........................................34Archetti, Roseann ..............................20, 66Arnold, Douglas L. ..............5, 7, 39, 44, 54Arnold, Kena .......................................4, 19Ascherio, Alberto .....................................24Asemota, Joseph I. ...................................78Avila, Mirla .............................................78

BBabajide, Lukmon ...................................79Backus, Deborah .................................3, 69Baert, Ilse ................................................77Balcer, Laura J. ........................................54Baldinetti, Francesca ..........................51, 61Balto, Julia M. ...................................61, 85Bando, Mauricio O., Sr. ..........................19Bar, Judi ..................................................76Bardhi, Konstantina ................................81Bargiela, David ........................................26Barkhof, Frederik ................................7, 39Barla, Annalisa ........................................69Barnes, Jennifer L. ...................................61Barone, Donald A. ....................................3Bar-Or, Amit ...........................................44Bass, Ann D. ...........................................35Battaglia, Mario Alberto ............................9Baynard, Tracy...........................................8

Beatty, Mark ........................................5, 43

Bedra, McKenzie E. .................................31

Beier, Meghan ...................................23, 33

Benamor, Myriam ...................................41

Benedict, Ralph H.B. ..............................17

Benich, Marisa ........................................21

Bennett, Susan E. ......................................1

Ben-Zacharia, Aliza .................................35

Berrigan, Lindsay ....................................80

Beswick, Christine .....................................3

Bethoux, Francois ....................................76

Bever, Christopher T., Jr. .........................29

Bhan, Virender ........................................24

Bilodeau, Brigitte ....................................19

Bishop, Malachy ......................................75

Bisson, Etienne J. ....................................69

Bjoraker, Kendra .....................................46

Bjorklund, Gregory .................................49

Bohling, Corinne J. .................................78

Boster, Aaron.....................................13, 36

Boström, Katrin Å ...................................14

Botvinick, Jason ..........................22, 66, 84

Bouchard, Jean-Pierre ..............................41

Bove, Marco ..............................................9

Bove, Riley ..............................................26

Boyko, Alexey............................................5

Bradford, Elissa Held...............................77

Brandstadter, Rachel ................................15

Braun, Lauren K......................................72

Brette, Sandrine .......................................61

Brichetto, Giampaolo ....................9, 31, 69

Britton, Karlene ......................................48

Bromley, Lacey ..........................................1

Brosseau, Marie-Sarah Gagne ..................42

Brown, Theodore R. ................................79

Browne, Catherine M. .............................72

Bruce, Amanda ........................................86

Bruce, Jared M. .......................................86

Buck, Ariane F. ........................................70

Buhse, Marijean ....................12, 15, 20, 81

Bukley, Brieana ........................................67

Bulgheroni, Maria ...................................31

Bumstead, Barbara ......................12, 20, 81

Bunyan, Sheri L. .....................................65

Burdett, Blake .........................................69

Burgess, Kathy ........................................44

Burke, Therese V. ....................................15

Burns, Meghan ........................................76

Burton, Erik ........................................7, 58

CCadavid, Diego .......................................63Calabresi, Peter A. .............................71, 85Calkwood, Jonathan ..........................37, 45Camac, Ann ............................................38Camu, William .......................................47Canas, Angela ..........................................46Canzonieri, Ana M. ...........................19, 70Caon, Christina .......................................49Cardinal, Ryan ........................................70Carriere, Lucille J. .......................18, 20, 21Carruthers, Robert L. ..............................24Caruana, Alison .........................................3Cascione, Mark .................................36, 50Casey, Blathin .....................................1, 72Castrillo, Carmen ....................................63Cavalier, Steven ...........................41, 61, 63Centonze, Diego ...............................45, 53Chaves, Claudia ......................................38Chen, Yun ...............................................63Cheng, Yan ..............................................50Cherry, Shenira .......................................12Chiang, Chen Chun ..........................71, 85Chiaravalloti, Nancy D. ............................5Chin, Peter ........................................37, 47Chinea, Angel .........................................25Chitnis, Tanuja ..................................24, 26Chiu, Chung-yi .......................................85Chua, Alicia ............................................26Cinar, Bilge Piri .......................................56Clare-Hunter, Isabelle St. ..........................6Cofield, Stacey S............................6, 36, 60Cohan, Stanley ........................................37Cohen, Evan T. ...................................3, 70Cohen, Jeffrey A. ...................37, 42, 46, 59Coleman, Brandon ..................................66Comber, Laura E. ......................................9Comer, Adam D. .....................................80Comi, Giancarlo ...............................41, 44Compston, D. Alastair S. ....................7, 46Conomy, John P. .....................................11Coote, Susan B. .........................1, 9, 32, 72Corboy, John ...........................................30Costa, Silvana L.........................................5Coyle, Patricia K. ..............................61, 87Cramer, Deb ...........................................42Cree, Bruce A.C. .....................................37Cross, Anne H. .......................................50Cudrici, Cornelia ....................................29

Author Index

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Author Index

Custy, Lisa ...............................................62Cutter, Gary ..................................6, 36, 60Czlonkowska, Anna .................................41

DDa, Kayleigh ...........................................52d’Amico, Enrico ......................................31Dangond, Fernando .............36, 41, 45, 50,

56, 60, 87da Silva, Gisela Bevilacqua Rolfsen Ferreira ...32Delfolie, Astrid ........................................51Delgado, Silvia ........................................16DeLuca, John ......................................5, 64Denney, Thomas .....................................58Derfuss, Tobias ..................................54, 55Desanctis, Cara .......................................80DeToledo, John .......................................78Devos, Hannes ....................................3, 62Diaz-Cruz, Camilo ..................................26Dick, Gregory J. ........................................6Dionne, Caitlin A. ..................................38Dong, Qunming .....................................63Doniger, Glen .........................................20Donnelly, Alan ........................................32Dorans, Kirsten S. ...................................24DuChane, Janeen ....................................67Durairaj, Chandra ...................................46Dworetsky, Sarah .......................................8

EEdan, Gilles .............................................39Edwards, Keith R. .......................35, 61, 63Edwards, Natalie C. ................................38Ehde, Dawn ............................................23Ehrman, Jane Pernotto ............................76Elkins, Jacob ...........................................43Elm, Heidi ................................................1Ensari, Ipek .............................................61Erwin, April ............................................57Euaparadorn, Emil ..................................75Eustis, Heather L. ................................2, 78Evans, Charity .........................................48Evilevitch, Vladimir...........................45, 53

FFabian, Michelle ......................................14Facchinetti, Sara ......................................31Fafard, Lori .................................12, 20, 81Fan, Youran ...................................2, 18, 20Fang, Juanzhi ..................36, 50, 56, 60, 87Farnett, Lisa ............................................63Farsani, Maziar Eslami.............................27Fauchoux, Nicolas ...................................51Fernhall, Bo...............................................8Feys, Peter ...............................................77

Fiest, Kirsten M. .....................................80Filipi, Mary .............................................49Finkelstein, Joseph ..................................31Finlayson, Marcia ..............................69, 85Fiorini, Samuele ......................................69Fisher, Nadine M. .............................10, 71Fisk, John D. .....................................24, 80Fjeldstad, Cecilie .....................................30Flood, Sara ........................................66, 84Floyd, Rebecca M. ...............................4, 19Foley, Frederick W. ................20, 22, 66, 84Forwell, Susan ...................................72, 82Fox, Edward J. .................35, 39, 40, 42, 46Fox, Robert J. ....................6, 36, 39, 57, 60Francisco, Jean I. .....................................19Frean, Molly ......................................40, 52Freedman, Mark S. ................39, 40, 41, 87Freeman, Jessica D. .................................16Friedman, Howard ..................................48Fritz, Nora E. ....................................71, 85

GGambon, Shannon ..................................65Gandhy, Chetan ......................................34Ganguly, Rik ...........................................38Gappmaier, Eduard .................................77Garcia, Christina .....................................23Gardner, Lidia ...........................................7Garg, Hina ..............................................77Garren, Hideki ........................................44Genova, Helen ..........................................5Ghahari, Setareh ......................................82Giacomo, Maria C. ...........................19, 70Giovannoni, Gavin ......................42, 43, 59Glanz, Bonnie I. ......................................26Glukhovsky, Lisa ...................20, 22, 66, 84Glusman, Morgan B. ...............................86Golan, Daniel..........................................20Gold, Ralf .............................39, 43, 57, 61Goldman, Dori .......................................72Goldman, Myla D. ..................................63Goldwasser, Eric ........................................3Golubic, Mladen .....................................76Gooch, Kaye ...........................................78Goverover, Yael ........................................64Grass, Daymet D. ....................................43Greeke, Emily .........................................26Green, Rivka ...........................................23Greenberg, Ben .................................18, 20Greenberg, Steven J. ............................5, 43Greenfield, Jamie .....................................33Gregory, Tyler J. ......................................65Griffith, Garett ..........................................8Gromisch, Elizabeth S. ............................84

Gudesblatt, Mark ..................12, 13, 20, 81Gulick, Elsie E. .......................................15Guo, Zuyu ..............................................51

HHaas, Shannon L. ....................................64Halper, June ................................15, 45, 53Han, Jian .................................................58Hannigan, Christine ................................15Hara-Cleaver, Claire ................................11Hard, Marjie ...........................................46Hardy, Eleana ..........................................66Harel, Brian T. ........................................19Harlow, Danielle .....................................30Harrison, Michele ...................................16Hartoonian, Narineh ...............................21Hartung, Hans-Peter ...7, 39, 42, 44, 46, 59Haselkorn, Jodie K. .................................21Hauser, Stephen L. ..................................44Havrdova, Eva .....................5, 7, 42, 43, 46Hawker, Kathleen ............36, 48, 54, 55, 60Hawkins, Laura .......................................69Hayes, Moira P. .......................................44Hayes, Sara ..........................................1, 72Hayward, Brooke ..............................41, 45Healy, Brian C. ........................................26Hellwig, Kerstin ........................................2Hemmer, Bernhard .................................39Hempel, Alexandra ..................................16Henneghan, Ashley ...................................3Herrera, Vivian ........................................48Herriott, Denise A. ..................................48Hertz, Deborah .......................................33Hillen, Machteld E. .................................27Hillman, Charles H. ................................17Hillman, Lynda R. ..................................44Hoffnung, Gabriel .................20, 22, 66, 84Holliday, Stephanie S. .............................59Hotermans, Christophe ...........................37Huang, DeRen ..................................45, 53Hubbard, Elizabeth A. .......................28, 61Hughes, Abbey ........................................21Hughes, Bruce L. ....................................45Hughes, Christina ...................................21Hung, Serena ..........................................54Hunt, Thomas L. ....................................46

Hunter, Samuel F.......................................6

Hutaff-Lee, Christa .................................46

Hyland, Megan .......................................25

Hynes, Sinéad M. ..............................72, 82

IIonete, Carolina ......................................46

Islam, Zahur ............................................52

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Author Index

JJackson, Scott ..........................................63

Jacques, Francois H. ..........................19, 74

Jeffery, Douglas .......................................47

Jennings, Nina.........................................64

Jerve, Sue...................................................1

Jiang, Allen ........................................71, 85

Jiang, Ying ...............................................46

Johnson, Kurt ..........................................33

Johnson, Luisa C. ....................................72

Johnston, Lisa .........................................78

KKahraman, Turhan ............................56, 74

Kakarieka, Algirdas ..................................44

Kalb, Rosalind C. ....................................33

Kalina, Jennifer .................................23, 72

Kalinowski, Pawel .............................19, 74

Kalita, Lauren..........................................65

Kalra, Jitender .........................................12

Kantor, Daniel ..........................................6

Kappos, Ludwig ................5, 37, 39, 41, 44

Karpatkin, Herbert I. ....................8, 75, 76

Kasten, Linda ....................7, 35, 42, 46, 59

Kaufman, Michael .....................................5

Kavak, Katelyn S. ..............................25, 26

Kavountzis, Jason ......................................9

Keller, Jennifer ..................................71, 85

Kendter, Jonathan ...................................57

Kern, Ralph .............................................52

Khatri, Bhupendra ..................................61

Kieseier, Bernd C. ...................................54

Kingwell, Elaine ......................................24

Kinkel, Revere P. .....................................66

Kinnett-Hopkins, Dominique L. .............82

Kivlahan, Daniel .....................................21

Klaren, Rachel E..................................8, 73

Klingelschmitt, Gaelle .............................44

Knapp, Courtney ....................................30

Knox, Katherine ......................................48

Ko, John J. ........................................48, 65

Koch, Kimberly .......................................65

Koffman, Boyd M. ..................................59

Kolb-Sobieraj, Channa ............................26

Kosehasanogullari, Gorkem ...............56, 74

Kostich, Lori A. .......................................73

Kozma, Chris M. .....................................49

Kraft, George H. .....................................33

Kramer, John .....................................49, 57

Kremenchutzky, Marcelo .........................57

Krieger, Stephen ....................14, 15, 25, 50

Kruszewski, Adam M. .............................29

Kurukulasuriya, Nuwan C. ......................39

LLaGanke, Christopher .......................37, 61

Laing, Lisa ...............................................80

Lancia, Samantha ..............................28, 85

Langer-Gould, Annette M. ......................67

Larkin, Aidan ..........................................72

Lawson, Kenneth A. ................................58

Leahy, Leslie ......................................45, 53

Learmonth, Yvonne C. ......................82, 85

Leigh-Pemberton, Richard ......................46

Leite, Fabio de Lima ................................32

Leppert, David ........................................44

Levasseur, Victoria A. ..............................85

Levin, Judith B. .......................................22

Levin, Michael ..........................................7

Lewis, Kimberly ..................................4, 19

Li, David K. ......................................50, 60

Li, Yunfeng ..............................................48

Lindwall, Jennifer ....................................46

Lipe, Hillary ............................................42

Liu, Ken ..................................................63

Liu, Shifang .............................................54

Livingston, Terrie ..............................25, 67

Lo, Albert C. .....................................27, 83

Locklear, Julie C. .........................40, 49, 52

Longbrake, Erin E. ..................................50

Lopez, Eliot .........................................4, 19

Lotya, Juzer .............................................65

Loud, Sara ...............................................66

Lublin, Fred D. .......................................44

Lunven, Catherine...................................51

Lusher, William .......................................64

Lyman, Michelle .....................................34

Lynch, Sharon G. ....................................86

MMa, Wei ....................................................5

Maldonado, Janice ..................................16

Malik, Muhammad T. .............................26

Maloni, Heidi W. ........................15, 31, 32

Manella, Christine ...................................69

Mann, Monica ........................................37

Manthis, Joan ..........................................46

Manzoor, Adil ...........................................3

Marasigan, Rhul ......................................85

Marcus, Evan B. ......................................17

Margolesky, Jason H. ...............................51

Margolin, David H. ..........7, 35, 42, 46, 59

Marques, Fernanda M. ............................19

Marrie, Ruth Ann..............6, 24, 36, 60, 80

Martin, Bess ............................................63

Martin, Tara ............................................11

Massa, Jennifer ........................................24

Mattson, David H. ..................................80Matusik, Mark ........................................67McBurney, Robert N. ..............................66McCully, Kevin .......................................69McGowan, Kayla...............................11, 12McKay, Kyla ............................................80McNeal, Sandre .............................6, 36, 60Medvedev, George ...................................52Meier, Daniela Piani ......................7, 37, 47Meinel, Michael ......................................47Meka, Venkata .........................................37Meltzer, Leslie .............................25, 37, 66Mendelowitz, Elana ...........................66, 84Meng, Xiangyi ...................7, 52, 54, 55, 60Menzin, Joseph..................................40, 52Metz, Luanne M. ....................................33Meyer, Diane ...........................................78Mikol, Daniel ..........................................63Miles, Zipporah.......................................31Miller, Aaron E. ....................36, 40, 50, 63Miller, Colleen E. ....................................49Miller, Joseph ..........................................78Miller, Rick T. .........................................67Miller, Wendy .........................................44Minitti, Judith .........................................80Miravalle, Augusto A. ........................16, 30Mok, Calvin ......................................11, 12Molina-Guzmán, Isabel ...........................85Montalbán, Xavier .............................39, 43Moore, Helena ........................................44Morisky, Donald E. .................................12Morrison, Janet .........................................3Moses, Harold .........................................37Motl, Robert W. .........8, 17, 28, 29, 30, 61,

73, 76, 82, 85Mullur, Jyotsna ........................................52Munger, Kassandra ..................................24Munsell, Michael .....................................52Musgrave, Daniel ....................................76Muth, Stephanie ......................................70

NNaismith, Robert T............................28, 85Nativ, Avi ................................................74Navaratnam, Prakash ...............................48Nazareth, Tara A. .........................48, 58, 65Nelson, Jill R. ....................................11, 52Ness, Abigail R. .......................................86Neugebauer, Volker .................................78Newland, Pamela K. ....................31, 53, 83Newsome, Scott D. .....................45, 53, 54Ng, Alexander V. .....................................65Nguyen, Vingh ........................................29Nicholas, Jacqueline ..........................54, 55

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Author Index

Nickel, Darren ........................................48Nieland, Jette G.K. ..................................55Nieland, John D. .....................................55Nielsen, Soeren........................................55Nilsagård, Ylva ........................................14Novas, Mark ............................................57

OObeidat, Ahmed Z. ...........................23, 28O’Brien, Lauri .........................................84O’Connor, Eileen ....................................25O’Connor, Paul .......................................41Okai, Annette..........................................63Okwuokenye, Macaulay ..........................37Olango, Weredeselam ..............................27Oliveira, Anselmo Gomes de ...................32Oliver, Brant J. ........................................53Olson, Kayla M. ......................................83Olsson, Tomas P. .....................................41O’Neill, Caitriona ...................................65Ontaneda, Daniel ..............................54, 55Ortega, Melissa .......................................16Ousley, Cherita .......................................76Ozakbas, Serkan ................................56, 74Ozen, Gulden..........................................43

PPalomeque, Ana ......................................67Pandey, Krupa .........................................23Paquette, Chantal ..............................19, 74Pardo, Gabriel .........................................30Parikh, Nishant .........................................3Park, David ...............................................8Pasternak, Eliana .....................................66Patten, Scott B. .......................................80Pedullà, Ludovico ......................................9Pence, Brandt ..........................................73Peterson, Elizabeth ..................................69Petroff, Nicolas ........................................56Phillips, Amy L. ....................38, 40, 49, 52Phillips, J. Theodore ................................57Piccio, Laura ...........................................50Picone, Mary Ann .........................9, 20, 66Pilutti, Lara A. .............................28, 73, 76Pirvoaica, Mihaela D. ..............................24Pleimes, Dirk ..........................................39Plummer, Prudence .............................2, 78Pohl, Christoph .......................................39Ponzio, Michela .................................31, 69Portnoy, Jeffrey G. ...................................66Potts, James .............................................39Pozzilli, Carlo ..........................................57Prince, Jerry.............................................85Purtill, Helen ..........................................32

QQuinn, Helen ..........................................84

RRadue, Ernst-Wilhelm.......................43, 47

Rajendra, Savanur Deepak.......................70

Rametta, Mark ........................................56

Rammohan, Kottil ..................................16

Ramsbottom, Michael J. ..........................50

Rana, Jitesh .............................................57

Ranchet, Maud .......................................62

Rao, Gautam K. ......................................29

Rarick, Madelyn B. ...................................6

Raval, Bhrugav ........................................27

Ravenscroft, Jennifer ...............................49

Ray, Andrew D. .................................10, 71

Reder, Anthony T. ...................................87

Reeves, Sandra .........................................23

Rensel, Mary R....................................2, 21

Repovic, Pavle ...........................................7

Reynolds, Mary Ann ...............................69

Reynolds, Piper .......................................33

Reznik, Jacob (Jake) ................................11

Ribeiro, Andira A. ...................................19

Richards, Kristin M. ................................58

Riser, Emily S. ...................................58, 63

Riskin, Barry J. ........................................85

Ritter, Shannon ...........................36, 37, 47

Robb, Jessica F. ........................................25

Robertson, Christopher .....................45, 53

Robertson, Derrick ..................................34

Robinson, Alysha M. ...............................59

Roeing, Kathleen L..................................29

Roessler, Richard T. .................................75

Rog, David ..............................................64

Rose, John .................................................5

Rosenberg, Angela ...................................78

Ross, Amy Perrin ...............................49, 56

Ross, Elaine O. ..................................74, 75

Ross, Lindsay A. ......................................59

Royal, Walter, III .....................................29

Ruiz, Jennifer A. ................................27, 83

Rumrill, Phillip D. ..................................75

Rus, Horea ..............................................29

Rus, Violeta .............................................29

Russell, Akimyo C. ..................................32

Russo, Liliana ....................................19, 70

Rutter, Katie ............................................23

Ryan, Jessica L. ........................................70

SSaake, Anna .............................................56

Sabatella, Guido ................................45, 53

Salinas, Gregory D. .................................66Salter, Amber R. ..................................6, 60Samkoff, Lawrence ..................................25Sammarco, Carrie L. ...............................80Sandbrink, Rupert ...................................39Sandroff, Brian M. ............................17, 73Santos, Lucas F., Sr. .................................19Saraceno, Taylor ......................................26Sasane, Rahul ..............................48, 58, 65Saulino, Michael .....................................13Savci, Sema .............................................74Schaefer, Sara ..........................................21Schairer, Laura C. ....................................84Schembri, Adrian J. ...........................19, 74Schippling, Sven ......................................39Schmidt, Hollie .......................................66Schofield, Lesley ......................................60Schreiner, Teri ...................................30, 46Schreiner, Thomas ...................................56Schreyer, Robert J. ...................................75Schroeder, Christopher ..............................2Schulze, Andrea .......................................39Scott, John D. .........................................33Selmaj, Krzysztof W............5, 7, 35, 43, 44,

46, 57Settle, Jill R. ......................................31, 32Seze, Jerome de........................................41Shang, Shulian ........................................54Sheikh, Zubeda B. ...................................27Sheremata, William .................................16Sherman, Kristen B. ..................................6Shirani, Afsaneh ......................................24Silva, Taislandia .......................................19Simnad, Virginia I. ..................................79Singer, Barry ............................................59Sloan, Alicia ............................................21Sloan, Jessica H. ................................66, 84Smoot, Kyle E. ........................................37Smrtka, Jennifer ......................................25Snyder, Stacey..........................................84Soares, Robert J. ......................................34Soliman, Sara ............................................3Sørensen, Per S. .......................................35Sosnoff, Jacob J. ..........................29, 30, 76Sosowsky, Esther .....................................76Sperling, Bjorn ........................................54Sprenger, Till .....................................36, 43Stam, Darren ...........................................63Staskon, Francis .......................................67Steele, Miranda B. ...................................58Steelman, Andrew J. ................................73Stefoski, Dusan .......................................43Steiner, Deb ............................................63Stepleman, Lara ...................................4, 19

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Author Index

Stewart, Thomas M. ................................16

Stimmel, Marnina B. ...............................66

Stobbe, Gary .....................................33, 42

Stough, Darlene K. ..................................76

Stuifbergen, Alexa .....................................3

Suarez, Gustavo .......................................39

Suh, Jimin ...............................................65

Sullivan, Amy ..............................18, 20, 21

Sullivan, Cynthia ...............................12, 20

Sung, Jong ...............................................76

Sutherland, Samuel .................................38

Sutton, Bradley P. ....................................28

Sweetser, Marianne T. ..........................5, 57

Sylvester, Lauren ......................................56

TTacchino, Andrea ..........................9, 31, 69

Talbot, Paul .............................................64

Tant, Mark ..............................................62

Tarlow, Leslie ..........................................67

Tegla, Cosmin A. .....................................29

Tenenbaum, Nadia ..................................60

Teter, Barbara E. ................................25, 26

Thangavelu, Karthinathan .................40, 41

Thelen, Joan M. ......................................86

Thomas, Nina .........................................36

Thotam, Smitha ................................12, 81

Tierney, Rachel ..........................................9

Tomic, Davorka ......................................36

Tompkins, Sara Anne ........................65, 84

Toomey, Thomas .................................4, 19

Tornatore, Carlo ................................34, 37

Tornes, Leticia ...................................16, 51

Tornes, Luis F. .........................................16

Traboulsee, Anthony ...............7, 44, 50, 60

Tracy, Tracy Flemming ............................63

Travis, Lori Hendin .................................63

Tremlett, Helen .................................24, 80

Triche, Elizabeth W. ..........................27, 83

Truffinet, Philippe .............................40, 41

Turner, Aaron P. ......................................21

Turner, Timothy ......................................51

Turpault, Sandrine ..................................51

Tuttle, Lindsay O. ...................................27

Tyry, Tuula ....................................6, 36, 60

UUnruh, Kent ............................................33

Uszynski, Marcin K. ................................32

VVerdun, Elisabetta ...................................47

Vermersch, Patrick ...................................41

Vernon, Karen .........................................64

Verri, Alessandro .....................................69

Vincent, Hunter ........................................9

Vogelreuter, Julika ...................................56

Vorobeychik, Galina ....................11, 12, 52

WWagner, Joanne M. ............................77, 85

Wajda, Douglas A........................29, 30, 76

Walker, Aljoeson .....................................25

Wall, Winona ..........................................33

Wallin, Mitchell T. ............................31, 32

Wan, Cecilia ............................................68

Wang, Guoqiao .......................................60

Wang, Ping ...............................................5

Wang, Weizhen .......................................27

Ward, Sarah M. .......................................77

Warren, Sharon .......................................80

Warth, John ............................................41

Watson, Crystal .......................................63

Weinacker, Virgina R. .............................63

Weinstock-Guttman, Bianca .............25, 26

Weir, Joseph P. .........................................30

Weiss, Elliott .....................................11, 12

Weiss, Marcie ....................................11, 12

Welch, Michaela ......................................16

Weller, Ivonne .........................................56

Wesley, Craig D.......................................68

Wesley, Sarah F. .......................................14

Wetter, Nathan C. ...................................28

Wicklein, Eva-Maria ...............................39

Wiendl, Heinz ...........................................5

Wilken, Jeffrey ..................................12, 20

Williams, Alexis A. ..................................78

Williams, Mitzi J. ....................................25

Willis, Alissa ............................................11

Wingrove, Catherine B. .....................16, 68

Winn, Karen ...........................................53

Wissemann, Karl .....................................12

Wolfson, Christina ..................................80

Wolinsky, Jerry S. ....................................41

Woods, Jeffrey A......................................73

Wright, Charlie .........................................8

Wu, Yaoshi ..............................................43

Wundes, Annette ...............................33, 42

XXian, Steven ............................................81

YYang, Zhen ..............................................85

Ye, Chuyang ............................................85

Yin, Guosheng ........................................52

You, Xiaojun ...............................25, 45, 53

Youn, Clover E. .......................................20

Yu, Tzy-Chyi ...........................................58

ZZabeti, Aram .....................................23, 28

Zackowski, Kathleen M. ....................71, 85

Zakalik, Karen .........................................25

Zarif, Myassar..............................12, 20, 81

Zemon, Vance .........................................22

Zervas, Michael .........................................8

Zhang, Annie ..........................................39

Zhang, Ray .............................................57

Zhao, Guojun .........................................50

Zhao, Yinshan .........................................24

Zhou, Huanxue .................................48, 58

Zhu, Feng ...............................................24

Ziemssen, Tjalf ........................................56

Zinberg, Elishiva .....................................76

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