THE MAYO-CLINIC CANADIAN COOPERATIVE TRIAL OF SULFASALAZINE IN ACTIVEMULTIPLE-SCLEROSIS

Objective: To determine whether sulfasalazine is better than placebo i n slowing disability progression in MS. Methods: In this randomized, d ouble-blind, placebo-controlled phase III trial, 199 patients with act ive relapsing-remitting (n = 151) or progressive (n = 48) MS were eval uated at 3-month intervals for a minimum of 3 years (94% completed 3 y ears of follow-up; mean follow-up, 3.7 years). MRI studies were perfor med at 6-month intervals on a subset of 89 patients. Results: Sulfasal azine failed to slow or prevent disability progression as measured by the primary outcome (confirmed worsening of the Expanded Disability St atus Scale [EDSS] score by at least 1.0 point on two consecutive 3-mon th visits). Sulfasalazine influenced favorably a number of secondary o utcomes during the first 18 months of the trial (e.g., annualized rela pse rate, proportion of relapse-free, patients; progressive subgroup o nly: rate of EDSS progression at 1 and 2 years, median time to EDSS pr ogression) but these positive findings were not sustained into the sec ond half of the trial. Conclusions: Sulfasalazine does not prevent EDS S score progression in the subset of MS patients studied by this proto col. Treatments may improve relapse-related outcomes in MS, at least t emporarily, without providing sustained slowing of EDSS progression. P hase III MS trials should be of sufficient length to determine a meani ngful impact on disease course.