IMPACT OF INTERFERON BETA-1A ON NEUROLOGIC DISABILITY IN RELAPSING MULTIPLE-SCLEROSIS

Background and Objective: A phase III double-blind, placebo-controlled clinical trial demonstrated that interferon beta-1a (IFN beta-1a) (Av onex, Biogen) significantly delayed progression of disability in relap sing MS patients. The primary clinical outcome was time from study ent ry until disability progression, defined as greater than or equal to 1 .0 point worsening from baseline Kurtzke Expanded Disability Status Sc ale (EDSS) score persisting for at least two consecutive scheduled vis its separated by 6 months. The objective of this study was to examine the magnitude of benefit on EDSS and its clinical significance. Method s: Post hoc analyses related to disability outcomes using data collect ed during the double-blind, placebo-controlled phase III clinical tria l. Results: (1) Clinical efficacy related to disability did not depend on the definition of disability progression. A significant benefit iu favor of IFN beta-1a was observed when greater than or equal to 2.0 p oint worsening from baseline EDSS was required or when worsening was r equired to persist for greater than or equal to 1.0 year. (2) Placebo recipients who reached the primary clinical outcome worsened by a larg er amount from baseline EDSS than did IFN beta-1a recipients who reach ed the primary study outcome. (3) Significantly fewer IFN beta-1a reci pients progressed to EDSS milestones of 4.0 (relatively severe impairm ent) or 6.0 (unilateral assistance needed to walk). (4) Cox proportion al hazards models demonstrated that the only baseline characteristic s trongly correlated with longer time to disability progression was IFN beta-1a treatment. Conclusions: The primary clinical outcome for the I FN beta-1a clinical trial underestimated clinical benefits of treatmen t. Results in this report demonstrate that IFN beta-1a treatment is as sociated with robust, clinically important beneficial effects on disab ility progression in relapsing MS patients.