Cross-Sectional Study Assessing Long-Term Safety Of Interferon-Beta-1b For Relapsing-Remitting Ms

Objective: The 16-Year Long-Term Follow-Up (LTF) to the pivotal interferon-beta-1b (IFN beta-1b) trial explored clinical, MRI, cognitive, and patient-reported outcomes. Here, we report the safety assessments.Methods: In the pivotal study, 372 patients were randomized to placebo (n = 123), IFN beta-1b 50 mu g (n = 125), or IFN beta-1b 250 mu g (n = 124) subcutaneously every other day for up to 5 years. Sixteen years later, patients were asked to participate in this cross-sectional follow-up study. No particular therapy was stipulated during follow-up. Adverse events experienced since the pivotal trial were recorded. Neutralizing antibodies (NAbs) to IFN beta-1b were measured using the myxovirus protein A induction assay. Statistical analyses were descriptive.Results: In total, 88.2% of patients (328/372) were identified. Some centers achieved 100% ascertainment, obviating selection bias. Treatment-related adverse events (e.g., leukopenia and liver and thyroid dysfunction) reported by LTF participants were in keeping with those previously established. Based on a follow-up period that includes 2,000 patient-years of IFN beta-1b treatment, no new adverse events were observed that were associated with long-term IFN beta-1b exposure. By LTF, NAbs to IFN beta-1b disappeared in the majority (76%) of NAb-positive patients. NAb status during the pivotal study appeared to have no impact on long-term clinical and MRI outcomes. There were more deaths among patients assigned to placebo in the pivotal study (20/109 [18.3%]) compared with patients who received IFN beta-1b 50 mu g (9/108 [8.3%]) or IFN beta-1b 250 mu g (6/111 [5.4%]).Conclusion: The results from the 16-Year Long-Term Follow-Up study support the long-term safety of interferon-beta-1b therapy in multiple sclerosis.Classification of evidence: This study provides Class III evidence that patients with relapsing-remitting MS taking IFN beta-1b 50 mu g or 250 mu g subcutaneously every other day for up to 5 years, with subsequent unspecified treatment, have fewer deaths after 16 years of follow-up than similar patients on placebo for up to 5 years, with subsequent unspecified treatment (risk difference 11.5%, 95% confidence interval 4-19). Neurology (R) 2010; 74: 1877-1885