Identifying Patients with Relapsing-Remitting Multiple Sclerosis Who Have Aggressive Disease Characterized by Rapid Disability Progression (P05.093)

Abstract

Objective: Identify relapsing multiple sclerosis (RMS) patients with aggressive disease characterized by rapid disability progression. Background Criteria for identifying RMS patients with aggressive disease, which would be useful for clinical decision making and trial design, are currently unavailable. Design/Methods: The Multiple Sclerosis Collaborative Research Group (MSCRG) study was a phase 3, double-blind, placebo-controlled trial of intramuscular interferon beta-1a (IM IFNβ-1a) in patients with RMS. Patients received IM IFNβ-1a 30 μg or placebo once weekly for up to 2 years. Patients were required to have a baseline Expanded Disability Status Scale (EDSS) score of 1.0–3.5. Patients with a ≥2.0-point increase in EDSS score resulting in a score ≥4.0 by study end were considered to have aggressive RMS. The risk of a poor long-term outcome, defined as an EDSS score ≥8.0 at 8 years of follow-up, was calculated as an odds ratio from a logistic regression model comparing patients with and without aggressive RMS. Results: Few patients (n=39) had EDSS ≥4.0 over 2 years. Only 25 patients met the criteria for aggressive RMS. Among these patients, mean disease duration was 5.1±3.85 years, mean baseline age was 37.2±6.35 years, and mean baseline EDSS was 2.8±0.74. More patients in the placebo group (22%) than in the IM IFNβ-1a group (7%) met the criteria for aggressive RMS at 2 years ( P =0.0072). Thirteen patients reached the EDSS milestone of 8.0 (severe disability) by the end of the 8-year follow-up. The odds ratio for attaining severe disability was 31.4 (95% confidence interval, 7.7–127.8; P Conclusions: The proposed definition for aggressive RMS characterized by rapid EDSS progression appeared to be useful in identifying patients at high risk for a more severe long-term disease course with greater accumulation of physical disability. Supported by: Biogen Idec Inc. Disclosure: Dr. Scott has received personal compensation for activities with Novartis, Biogen Idec, Teva Neuroscience, and Genzyme as a consultant or speaker. Dr. Scott has received research support from the Pittsburgh Foundation. Dr. Laforet has received personal compensation for activities with Biogen Idec Inc. as an employee.Dr. Laforet holds stock and/or stock options in Biogen Idec Inc., which sponsored research in which Dr. Laforet was involved as an investigator. Dr. You has received personal compensation for activities with Biogen Idec as an employee.