INTERFERON BETA-1B IS EFFECTIVE IN RELAPSING-REMITTING MULTIPLE-SCLEROSIS - CLINICAL-RESULTS OF A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

We report a multicenter, randomized, double-blind, placebo-controlled trial of interferon beta-1b (IFNB) in 372 ambulatory patients with rel apsing-remitting multiple sclerosis (MS). Entry criteria included an E xpanded Disability Status Scale (EDSS) score of 0 to 5.5 and at least two exacerbations in the previous 2 years. One-third of the patients r eceived placebo, one-third 1.6 million international units (MIU) of IF NB, and one-third 8 MIU of IFNB, self-administered by subcutaneous inj ections every other day. The primary end points were differences in ex acerbation rates and proportion of patients remaining exacerbation-fre e. The annual exacerbation rate for patients receiving placebo was 1.2 7; for 1.6 MIU IFNB, 1.17; and for 8 MIU IFNB, 0.84 after 2 years. Exa cerbation rates were significantly lower in both treatment groups comp ared with the placebo group (8 MIU versus placebo, p = 0.0001; 1.6 MIU versus placebo, p = 0.0101; and 8 MIU versus 1.6 MIU, p = 0.0086), su ggesting a dosage effect. The reduction in exacerbation severity in th e 8 MIU group was attributable to a twofold reduction in the frequency of moderate and severe attacks. More patients in the 8-MIU group (n = 36) were exacerbation-free at 2 years compared with the placebo group (n = 18; p = 0.007). EDSS scores changed little from baseline in both the placebo and treatment arms. Accordingly, a significant change in disability could not be discerned in this trial. Finally, in serial MR Is, MS activity was significantly less in the high-dose IFNB group. IF NB treatment was well tolerated: the significant reductions in exacerb ation rates, severity of exacerbations, and accumulation of MRI abnorm alities occurred in the absence of serious side effects. IFNB is the o nly treatment that has substantially altered the natural history of MS in a properly controlled clinical trial.