Abstract Details

Title Confirmed Disability Progression Provides Limited Predictive Information Regarding Future Disease Progression

Topic Multiple Sclerosis

Presentation(s) S54 - Multiple Sclerosis: Disease Progression, Disease-modifying Therapy, and Clinical Considerations (3:54 PM-4:06 PM)

Poster/Presentation
Number 003

Objective To compare predictive performance of confirmed disability progression (CDP), Expanded Disability Status Scale (EDSS) scores, and MRI information on longer-term disease outcomes

Background CDP is a common outcome in clinical trials of multiple sclerosis (MS), but the predictive value of CDP for long-term disease outcomes compared with other clinical measures is uncertain.

Design/Methods Patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis study who met the following criteria were eligible for inclusion: (1) relapsing-remitting MS or a clinically isolated syndrome with EDSS ≤5; (2) a concurrent brain MRI; (3) a visit 24 months later; (4) ≥1 visit between the 24-month and index visit; (5) ≥1 additional visit after the 24-month visit. Using the first 3 clinical visits, 1,214 patients were classified based on the presence or absence of CDP at month 24. CDP was assessed as a predictor of time to EDSS 6 and time to secondary progressive multiple sclerosis (SPMS) using a Cox proportional hazards model. Additional models included combinations of the following predictors: month 0 EDSS, month 24 EDSS, age, disease duration, brain parenchymal fraction, and T2 lesion volume. Models were compared using the AIC as well as the hazard ratio (HR) for each predictor.

Results CDP was directionally associated with faster time to EDSS 6 in univariate analysis (HR=1.61; 95% CI [0.83, 3.13]). After adjusting for month 24 EDSS, CDP was directionally associated with slower time to EDSS 6 (adjusted HR=0.65 [0.32, 1.28]). Models including CDP had worse fit statistics compared with models using EDSS scores without CDP. When models included both clinical and MRI measures, T2 lesion volume improved fit statistics. Similar results were observed for time to SPMS.

Conclusions Our analysis demonstrates that CDP provides less predictive information about time to subsequent events compared with other MS clinical features.

Authors/Disclosures
Brian C. Healy PRESENTER	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.
Bonnie Glanz (Brigham and Women'S Hospital)	The institution of Ms. Glanz has received research support from CMSC. The institution of Ms. Glanz has received research support from NIH.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Diego Silva (Bristol-Myers Squibb Company)	Diego Silva has received personal compensation for serving as an employee of BMS. Diego Silva has received stock or an ownership interest from BMS.
	No disclosure on file
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 $10,000-$49,999 for serving as a Consultant for Siemens. 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 $500-$4,999 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. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Academic CME. 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.
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..

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