Abstract Details

Title Patterns and Predictors of Multiple Sclerosis Phenotype Transitions: A Longitudinal Analysis Using the CLIMB Study

Topic Multiple Sclerosis

Presentation(s) P5 - Poster Session 5 (11:45 AM-12:45 PM)

Poster/Presentation
Number 3-018

Objective To investigate how people with multiple sclerosis (pwMS) transition between phenotypes, within the Comprehensive Longitudinal Investigation of MS at the Brigham and Women’s Hospital (CLIMB) Study.

Background MS characteristics vary over time, but little is known about transitions and predictors of change among phenotypes

Design/Methods Retrospective analysis of US-based CLIMB Study. PwMS (18-65y) diagnosed between 2000/1/1–2010/12/31 were identified to allow ≥10y of data for descriptive and predictive analysis. PwMS were categorized by phenotype (relapsing-remitting MS[RRMS], primary-progressive MS[PPMS], active-secondary progressive MS[aSPMS], non-relapsing secondary-progressive MS[nrSPMS]). Demographics were extracted alongside disability scores (Expanded Disability Status Scale [EDSS]). Cox regression modelled time to MS diagnosis. Predictors of progression were determined by univariate analyses.

Results Of 565 with initial RRMS diagnosis, 95 (16.8%) transitioned to SPMS (median time 10.4y [range: 1.3–21.3y]). 56/95 (58.9%) transitioned to nrSPMS, and never relapsed. Of 39 pwMS with any aSPMS diagnosis, 32/39 (82.1%) transitioned to nrSPMS by last visit. Relative risk for time to reach EDSS level 3, 4, or 6, was lowest for RRMS patients (hazard ratio [HR]: 0.84 0.73, 0.68, respectively; all P<0.0001), and highest for PPMS patients (HR: 5.5, 10.7, 15.0, respectively; all P<0.0001), respectively. Older age at MS onset (HR[95% CI]: 1.05 [1.03-1.07]), higher baseline EDSS (1.42 [1.26-1.62]), and higher number of DMT switches (1.21 [1.11-1.32]) were significant predictors of shorter time to nrSPMS diagnosis (all P<0.001).

Conclusions Overall, 41% of the RRMS cohort who transitioned to SPMS overlapped with an active phenotype (aSPMS), while the majority (59%) transitioned without relapses (nrSPMS). Those who transitioned through aSPMS tended to be younger and more likely to have DMT escalation vs. those who transitioned without relapse (nrSPMS). Defining nrSPMS in addition to aSPMS should facilitate better patient management and aid timely intervention to aid delaying patients entering the progressive stage of MS.

Authors/Disclosures
Gauruv Bose, MD (The University of Ottawa and Ottawa Hospital Research Institute) PRESENTER	Dr. Bose has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bose has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Bose has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva Pharmaceuticals. The institution of Dr. Bose has received research support from Multiple Sclerosis Society of Canada.
Nupur Greene	Nupur Greene has nothing to disclose.
Brian C. Healy	The institution of Mr. Healy has received research support from Analysis Group. The institution of Mr. Healy has received research support from Bristol-Myers Squibb. The institution of Mr. Healy has received research support from Verily Life Sciences. The institution of Mr. Healy has received research support from Novartis. The institution of Mr. Healy has received research support from Merck Serono. The institution of Mr. Healy has received research support from Genzyme.
Howard L. Weiner, MD (Brigham and Women'S Hospital)	Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana Life Sciences. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for vTv Therapeutics. Dr. Weiner has stock in vTv Therapeutics. The institution of Dr. Weiner has received research support from National Institute of Health. The institution of Dr. Weiner has received research support from National MS Society. The institution of Dr. Weiner has received research support from Genzyme Corp. The institution of Dr. Weiner has received research support from Genentech, Inc. . The institution of Dr. Weiner has received research support from Verily Life Sciences LLC. The institution of Dr. Weiner has received research support from EMD Serono, Inc..
Lisa E. Farnett, PharmD (Sanofi)	Ms. Farnett has received personal compensation for serving as an employee of Sanofi. Ms. Farnett has stock in Sanofi.
Keiko Higuchi, Other (SANOFI genzyme)	Miss Higuchi has received personal compensation for serving as an employee of Sanofi. Miss Higuchi has received personal compensation for serving as an employee of Novartis. Miss Higuchi has received personal compensation for serving as an employee of Gilead Sciences . Miss Higuchi has received personal compensation for serving as an employee of Pfizer Inc. . Miss Higuchi has received personal compensation for serving as an employee of Zynx Health Inc. . Miss Higuchi has received stock or an ownership interest from Sanofi. Miss Higuchi has received stock or an ownership interest from Gilead. Miss Higuchi has received stock or an ownership interest from Novartis.
Tanuja Chitnis, MD, FAAN (Brigham and Women's Hospital)	Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Chitnis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche-Genentech. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave Biosciences. Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Chitnis has received research support from Novartis. The institution of Dr. Chitnis has received research support from Sanofi. The institution of Dr. Chitnis has received research support from Octave. The institution of Dr. Chitnis has received research support from Genentech-Roche. The institution of Dr. Chitnis has received research support from Tiziana Life Sciences. The institution of Dr. Chitnis has received research support from Bristol-Myers Squibb. The institution of Dr. Chitnis has received research support from Wesley Clover.

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