Glatiramer acetate in primary progressive multiple sclerosis: Results of a multinational, multicenter, double‐blind, placebo‐controlled trial

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Abstract
Objective To determine whether glatiramer acetate (GA) slows accumulation of disability in primary progressive multiple sclerosis. Methods A total of 943 patients with primary progressive multiple sclerosis were randomized to GA or placebo (PBO) in this 3‐year, double‐blind trial. The primary end point was an intention‐to‐treat analysis of time to 1‐ (entry expanded disability status scale, 3.0–5.0) or 0.5‐point expanded disability status scale change (entry expanded disability status scale, 5.5–6.5) sustained for 3 months. The trial was stopped after an interim analysis by an independent data safety monitoring board indicated no discernible treatment effect on the primary outcome. Intention‐to‐treat analyses of disability and magnetic resonance imaging end points were performed. Results There was a nonsignificant delay in time to sustained accumulated disability in GA‐ versus PBO‐treated patients (hazard ratio, 0.87 [95% confidence interval, 0.71–1.07]; p = 0.1753), with significant decreases in enhancing lesions in year 1 and smaller increases in T2 lesion volumes in years 2 and 3 versus PBO. Post hoc analysis showed that survival curves for GA‐treated male patients diverged early from PBO‐treated male subjects (hazard ratio, 0.71 [95% confidence interval, 0.53–0.95]; p = 0.0193). Interpretation The trial failed to demonstrate a treatment effect of GA on primary progressive multiple sclerosis. Both the unanticipated low event rate and premature discontinuation of study medication decreased the power to detect a treatment effect. Post hoc analysis suggests GA may have slowed clinical progression in male patients who showed more rapid progression when untreated. Ann Neurol 2007;61:14–24