Results of an Ongoing, Open-Label, Safety-Extension Study of Interferon Beta-1a (Avonex) Treatment in Multiple Sclerosis

Abstract In a phase III, double-blind, placebo-controlled, 2-year clinical trial, interferon beta-1a (IFN-β-1a, Avonex) treatment significantly delayed disability progression, decreased exacerbations, and reduced brain lesions on magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS). In this open-label, safety-extension study, we evaluated the longer-term safety and antigenicity of IFN-β-1a. An open-label, safety-extension study of IFN-β-1a, administered at a dose of 30 μg intramuscular (IM) per week in patients with MS, was initiated in May 1995. Subjects enrolled in this study included interferon-naive patients and patients who had prior treatment with either IFN-β-1a in the phase III trial, IFN-β-1b (Betaseron), or both. Safety was evaluated by assessment of adverse events, tolerability by treatment discontinuations, and antigenicity by measurements of neutralizing antibody (NAB) titers. The number of intravenous (IV) steroid courses required per patient per year was determined as a surrogate measure of clinical relapses. There were 382 patients enrolled, with a median duration of treatment, including the phase III trial, of 2.5 years. Twenty-eight percent of participants have been on treatment for at least 3 years. The adverse event profile was similar to that observed in the phase III trial. Injection site reactions were rare and injection site necrosis was not observed. The incidence of NAB to IFN-β over 30 months of treatment was approximately 5%. IFN-β-1a was well tolerated in subjects who had switched from IFN-β-1b. Seventy-seven percent of the patients with NAB to IFN-β-1b at study entry had lost their NAB by month 24 on IFN-β-1a treatment. There was a 47% reduction in IV steroid use in the safety-extension study in those who had previously received placebo in the phase III trial. Long-term treatment of MS patients with IFN-β-1a continues to have a favorable safety profile, with low NAB titers and continuing clinical benefit.