Placebo-controlled multicentre randomised trial of interferon β-1b in treatment of secondary progressive multiple sclerosis

Summary Background The beneficial effects of interferon β have only been shown for patients in the relapsing-remitting phase of multiple sclerosis (MS). The role of interferon β in the treatment of patients who are in the secondary progressive phase of the disease (SP-MS), and for whom no effective drug treatment is available, has not been assessed. Methods In this multicentre, double-masked, randomised, placebo-controlled trial, outpatients with SP-MS having scores of 3·0–6·5 on the Expanded Disability Status Scale (EDSS) received either 8 million IU interferon β-1b every other day subcutaneously, or placebo, for up to 3 years. The primary outcome was the time to confirmed progression in disability as measured by a 1·0 point increase on the EDSS, sustained for at least 3 months, or a 0·5 point increase if the baseline EDSS was 6·0 or 6·5. A prospectively planned interim analysis of safety and efficacy of the intention-to-treat population was done after all patients had been in the study for at least 2 years. Findings 358 patients with SP-MS were allocated placebo and 360 were allocated interferon β-1b; 57 patients (31 placebo, 26 interferon β-1b) were lost to follow-up. There was a highly significant difference in time to confirmed progression of disability in favour of interferon β-1b (p=0·0008). Interferon β-1b delayed progression for 9–12 months in a study period of 2–3 years. The odds ratio for confirmed progression was 0·65 (95% Cl 0·52–0·83). This beneficial effect was seen in patients with superimposed relapses and in patients who had only progressive deterioration without relapses. Positive results were also obtained regarding time to becoming wheelchair-bound, relapse rate and severity, number of steroid treatments and hospital admissions, as well as on magnetic resonance imaging variables. The drug was safe and side effects were in line with previous experience with interferon β-1b. The study was stopped after the interim results gave clear evidence of efficacy. Interpretation Treatment with interferon β-1b delays sustained neurological deterioration in patients with SP-MS. Interferon β-1b is the first treatment to show a therapeutic effect in patients with SP-MS.

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