Subcutaneous Interferon-ß1a Does Not Increase the Risk of Stroke in Patients with Multiple Sclerosis: Analysis of Pooled Clinical Trials and Post-Marketing Surveillance.

ABSTRACT

INTRODUCTION: Previous 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-ß1a (sc IFN-ß1a) using pooled data from clinical trials and post-marketing surveillance. METHODS: Seventeen phase II-IV Merck KGaA-sponsored trials of sc IFN-ß1a were assessed to estimate the stroke incidence rate (IR) and IR ratio (IRR) per 100 patient-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. RESULTS: In 17 clinical trials, 4412 patients were treated with sc IFN-ß1a for a total of 10,622 PY and 1055 patients with placebo for 2005 PY. The IR/100 PY (95% CI) of stroke was 0.025 (0.004, 0.150) in sc IFN-ß1a patients and 0.051 (0.008, 0.349) in placebo patients. The IRR for sc IFN-ß1a 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-ß1a treatment at any dose compared with placebo. Among sc IFN-ß1a patients, the IRR in those treated for < 2 years was 0.602 (0.159, 2.277) and for ≥ 2 years 0.469 (0.196, 1.124). Analysis of the safety database showed that the overall reporting rate for stroke was 13.286/10,000 PY. CONCLUSION: Safety data from both clinical trial and post-marketing settings indicate that treatment with sc IFN-ß1a does not increase stroke risk in patients with MS. FUNDING: Merck KGaA, Darmstadt, Germany.