RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED STUDY OF INTERFERON BETA-1A IN RELAPSING REMITTING MULTIPLE-SCLEROSIS/

Background Previous trials of interferon beta in multiple sclerosis (M S) have shown efficacy, but the degree of clinical benefit remains unc ertain, and the optimum dose is not known. We undertook a double-blind , placebo-controlled study in relapsing/remitting MS to investigate th e effects of subcutaneous interferon beta-1a. Methods 560 patients wit h Kurtzke expanded disability status scale (EDSS) scores of 0-5.0, fro m 22 centres in nine countries, were randomly assigned subcutaneous re combinant interferon beta-1a 22 mu g (n=189), or 44 mu g (n=184), or p lacebo (n=187) three times a week for 2 years. Neurological examinatio ns were done every 3 months. All patients had MRI twice yearly and 205 had monthly scans in the first 9 months of treatment. Analysis was by intention to treat. Findings Clinical data on 533 (95%) patients were available at 2 years. The relapse rate was significantly lower at 1 a nd 2 years with both doses of interferon beta-1a than with placebo (me an number per patient 1.82 for 22 mu g group, 1.73 for 44 mu g group v s 2.56 for placebo group: risk reductions 27% [95% CI 14-39] and 33 [2 1-44]). Time to first relapse was prolonged by 3 and 5 months in the 2 2 mu g and 44 mu g groups respectively, and the proportion of relapse- free patients was significantly increased (p < 0.05). Interferon beta- 1a delayed progression in disability, and decreased accumulated disabi lity during the study. The accumulation of burden of disease and numbe r of active lesions on MRI was lower in both treatment groups than in the placebo group. Interpretation Subcutaneous interferon beta-1a is a n effective treatment for relapsing/remitting MS in terms of relapse r ate, defined disability, and all MRI outcome measures in a dose-relate d manner, and it is well tolerated. Longer-term benefits may become cl earer with further follow-up and investigation.