Subcutaneous Interferon-β1a Does Not Increase the Risk of Stroke in Patients with Multiple Sclerosis: Analysis of Pooled Clinical Trials and Post-Marketing Surveillance

Abstract

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-β1a (sc IFN-β1a) using pooled data from clinical trials and post-marketing surveillance.MethodsSeventeen phase II–IV Merck KGaA-sponsored trials of sc IFN-β1a 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.ResultsIn 17 clinical trials, 4412 patients were treated with sc IFN-β1a 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-β1a patients and 0.051 (0.008, 0.349) in placebo patients. The IRR for sc IFN-β1a 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-β1a treatment at any dose compared with placebo. Among sc IFN-β1a 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.ConclusionSafety data from both clinical trial and post-marketing settings indicate that treatment with sc IFN-β1a does not increase stroke risk in patients with MS.FundingMerck KGaA, Darmstadt, Germany.

Association of multiple sclerosis with stroke: A comprehensive review

“…The objective of this investigation was to ascertain the factors that contribute to the hematological irregularities commonly observed in association with these therapies. Several reports have surfaced regarding the incidence of stroke and suboptimal neurological outcomes among patients diagnosed with MS who have undergone alemtuzumab therapy for a minimum of two doses at least 66,67 . They were perhaps linked to hypertension, hence MS patients on alemtuzumab must have frequent arterial pressure monitoring, with special attention paid to increases in systolic BP of more than 20 mmHg, or 20%.…”

Coexistence of neurofibromatosis type I, multiple sclerosis, and ischemic stroke: A case report and literature review

“…According to existing literature, treatment with subcutaneous interferon beta 1a (IFN-β1a) does not increase the risk of stroke in patients with MS. 31 Muhannad et al reported a case of alemtuzumab-induced simultaneous onset of autoimmune hemolytic anemia, alveolar hemorrhage, nephropathy, and stroke in a 52-year-old man that occurred 8 months after treatment initiation. 32 On the other hand, dimethyl fumarate (DMF) is hypothesized to provide clinical benefit to MS patients in case of ischemic stroke.…”