Multiple sclerosis patients using Rebif (interferon beta-1a) are not at an increased risk of a stroke, even if remaining on this therapy for more than two years, a study analyzing safety data from more than a dozen clinical trials and post-marketing surveillance shows.
The study “Subcutaneous Interferon-β1a Does Not Increase the Risk of Stroke in Patients with Multiple Sclerosis: Analysis of Pooled Clinical Trials and Post-Marketing Surveillance” was published in the journal Advances in Therapy.
Stroke is reported to be a prevalent comorbidity among MS patients, higher than in the general population. A stroke occurs when the blood supply to the brain is reduced or blocked, depriving the brain from oxygen and nutrients, and quickly leading to brain cell death.
Exact reasons for MS patients being at higher risk of stroke are not known. But it has been suggested that this risk is particularly high in the first year after diagnosis.
Researchers with Merck KGaA (known as EMD Serono in the U.S. and Canada), which markets Rebif, performed a pooled analysis of published clinical trials to assess if treatment had an impact on the risk of stroke in MS patients. They also analyzed stroke incidence in patients using the medicine in a “real-world” setting, after it began to be marketed (post-marketing surveillance data).
In total, the team compared stroke incidence among 4,412 MS patients treated with Rebif and 1,055 patients receiving placebo; all were participants in a total of 17 clinical trials (Phase 2, 3 and 4) sponsored by Merck.
The estimated incidence rate of stroke in those treated with Rebif and those receiving placebo was, respectively, 0.025 and 0.051 per 100 patient-years (a measure of incidence obtained by multiplying the number of persons at risk per time).
No significant difference was found in the likelihood of a stroke or the time to a stroke-related event between those using Rebif at any dose (11, 22, 33 or 44 micrograms; under-the-skin injections), compared to those given placebo (0.486 versus 0.496). Rather, a trend toward a lower stroke risk was seen among Rebif-treated patients compared with placebo, but this trend did not reach statistical significance.
Treatment duration was also assessed, and the incidence ratio of stroke in those treated for more than two years was not higher that than found among those using Rebif for two years or less (0.469 versus 0.602).
Researchers also analyzed the Merck Global Patient Safety Database, which gathers “real-world” data on adverse events via surveillance of patients taking the medicine following its market release. A total of 2,039 strokes were recorded, which represented an overall incidence rate of stroke of about 0.133 per 100 person-years, the study notes.
This incidence falls within that reported for the general population, which ranges from 0.114 to 0.350 cases per 100 person-years.
Stroke was primarily reported in patients with underlying diseases and risk factors for a stroke, including hypertension, smoking, diabetes, and high blood cholesterol levels. In most cases, patients continued to be treated with Rebif after the stroke.
The combination of both “real-world” clinical practice data from the Merck safety database and extensive data from randomized, controlled trials provides a “broad and robust assessment of the risk of stroke” in patients treated with Rebif, the researchers said.
“Safety data from both clinical trial and post-marketing settings suggest that treatment with sc IFN-β1a [Rebif] does not increase the risk of stroke in patients with MS” in the short- or long-term, the team concluded.