Key result
Subcutaneous interferon-beta1a reduces stroke risk ~51% versus placebo in multiple sclerosis.
Why the study?
Multiple sclerosis patients have a greater stroke risk than the general population but limited evidence exists on stroke risk with disease-modifying treatment such as subcutaneous interferon-β1a.
Does subcutaneous interferon-β1a increase the risk of stroke in patients with multiple sclerosis?
Meta-Analysis (n=4,570)
Double-blind
Randomized
Yes
Does subcutaneous interferon-β1a increase the risk of stroke in patients with multiple sclerosis?
Relative Risk: 0.486 (95% CI 0.238–0.995)
Absolute Event Rate: 0.025% vs 0.051%
Safety data from pooled clinical trials and post-marketing surveillance indicate that subcutaneous interferon-β1a does not increase the risk of stroke in patients with multiple sclerosis.
May support stroke safety with interferon-beta1a in MS; leaves open causal confirmation in randomized trials.
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-β1a (sc IFN-β1a) using pooled data from clinical trials and post-marketing surveillance. METHODS: Seventeen 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. RESULTS: In 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. CONCLUSION: Safety 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. FUNDING: Merck KGaA, Darmstadt, Germany.
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Sabidó et al. (2018) conducted a meta-analysis in Multiple Sclerosis (n=4,570). Subcutaneous Interferon-beta1a vs. Placebo was evaluated on Incidence rate of stroke per 100 patient-years (IRR 0.486, 95% CI 0.238-0.995). Subcutaneous interferon-beta1a did not increase the risk of stroke in patients with multiple sclerosis, demonstrating an incidence rate ratio of 0.486 compared to placebo.
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