Subcutaneous Interferon-1a Does Not Increase the Risk of Stroke in Patients with Multiple Sclerosis: Analysis of Pooled Clinical Trials and Post-Marketing Surveillance

IntroductionPrevious studies suggest that multiple sclerosis (MS) patients have a greater stroke risk than the general population but there is limited evidence of stroke risk in patients receiving disease-modifying treatment. We assessed stroke risk in MS patients treated with subcutaneous interferon-1a (sc IFN-1a) using pooled data from clinical trials and post-marketing surveillance.MethodsSeventeen phase II-IV Merck KGaA-sponsored trials of sc IFN-1a were assessed to estimate the stroke incidence rate (IR) and IR ratio (IRR) per 100patient-years (PY), and associated 95% confidence intervals (CI). The association of treatment duration with stroke was assessed through a Cox model. IR, IRR, and hazard ratio (HR) were adjusted by age, sex, presence of any comorbidity, and MS duration. Individual case safety reports were retrieved from the Global Patient Safety Database. The reporting rates of stroke were calculated and classified as medically confirmed or non-medically confirmed according to the source of each report.ResultsIn 17 clinical trials, 4412 patients were treated with sc IFN-1a for a total of 10,622PY and 1055 patients with placebo for 2005PY. The IR/100PY (95% CI) of stroke was 0.025 (0.004, 0.150) in sc IFN-1a patients and 0.051 (0.008, 0.349) in placebo patients. The IRR for sc IFN-1a vs placebo was 0.486 (0.238, 0.995) and the HR was 0.496 (0.235, 1.043) for time to stroke-related event for sc IFN-1a treatment at any dose compared with placebo. Among sc IFN-1a patients, the IRR in those treated for <2years was 0.602 (0.159, 2.277) and for 2years 0.469 (0.196, 1.124). Analysis of the safety database showed that the overall reporting rate for stroke was 13.286/10,000PY.ConclusionSafety data from both clinical trial and post-marketing settings indicate that treatment with sc IFN-1a does not increase stroke risk in patients with MS.FundingMerck KGaA, Darmstadt, Germany.