Randomized controlled trial of interferon- beta-1a in secondary progressive MS: Clinical results

Abstract

BACKGROUND: The beneficial effect of interferon beta on exacerbations in relapsing-remitting MS has been demonstrated repeatedly, but results concerning disability vary. OBJECTIVE: This multicenter, randomized, parallel-group, placebo-controlled study tested two doses of interferon beta-1a in patients with secondary progressive MS, which may include relapses but is dominated by accumulating disability. METHODS: A total of 618 patients received subcutaneous placebo or interferon beta-1a, 22 or 44 microg three times weekly for 3 years. Patients were assessed every 3 months. RESULTS: The primary outcome, time to confirmed progression in disability, was not significantly affected by treatment (hazard ratio, 0.83; 95% CI, 0.65 to 1.07; p = 0.146 for 44 microg versus placebo). Relapse rate was reduced from 0.71 per year with placebo to 0.50 per year with treatment (p < 0.001 for both doses). Significant treatment effects were seen on other exacerbation-related outcomes and on a composite measure incorporating five separate clinical and MRI outcomes. The hazard ratio for time to progression for the combined interferon beta-1a groups compared with placebo was 0.74 among patients reporting relapses in the 2 years before study (p = 0.055), and 1.01 for those without prestudy relapses (p = 0.934). An unexpected treatment-by-sex interaction favored women. The drug was well tolerated. CONCLUSIONS: Treatment with interferon beta-1a did not significantly affect disability progression in this cohort, although significant treatment benefit was observed on exacerbation-related outcomes. Exploratory post hoc analyses suggested greater benefit in women and in patients who had reported at least one relapse in the 2 years before the study.