Cross-sectional study assessing long-term safety of interferon-β-1b for relapsing-remitting MS

Abstract

Objective: The 16-Year Long-Term Follow-Up (LTF) to the pivotal interferon-β-1b (IFNβ-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), IFNβ-1b 50 μg (n = 125), or IFNβ-1b 250 μg (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 IFNβ-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 IFNβ-1b treatment, no new adverse events were observed that were associated with long-term IFNβ-1b exposure. By LTF, NAbs to IFNβ-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 IFNβ-1b 50 μg (9/108 [8.3%]) or IFNβ-1b 250 μg (6/111 [5.4%]).

Conclusion: The results from the 16-Year Long-Term Follow-Up study support the long-term safety of interferon-β-1b therapy in multiple sclerosis.

Classification of evidence: This study provides Class III evidence that patients with relapsing-remitting MS taking IFNβ-1b 50 μg or 250 μg 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).