A new analysis of more than a dozen clinical trials has shown no increase in stroke risk for patients with MS, who have shown a higher risk than the general population.
Saritha Venkatesh, MBBS
According to an analysis of safety data from 17 clinical trials and post-market data, the use of interferon ß-1a (Rebif, EMD Serono) for patients with relapsing multiple sclerosis (MS) does not increase their risk of stroke.1
Available literature has shown that patients with MS are at a higher risk of stroke compared to the general population,2 though limited evidence of the risk for stroke in those receiving disease-modifying therapy exists.
The analysis was conducted by Saritha Venkatesh, MBBS, and colleagues, and included several groups of patients: those who had been treated only with subcutaneous interferon ß-1a (n = 3515) and those treated with placebo only (n = 158), as well as a group of those treated with placebo followed by interferon ß-1a (n = 897). Those administered both the therapy and placebo were considered part of the placebo group until the start of interferon therapy, at which time they were included in the treatment group.
Ultimately, this new assessment showed an incidence rate per 100 patient-years was 0.025 (95% CI, 0.004 to 0.150) for those treated with subcutaneous interferon ß-1a compared to 0.0051 (95% CI, 0.008 to 0.349) for those administered placebo. The adjusted incidence ratio for therapy compared to placebo was 0.486 (95% CI, 0.238 to 0.995), and the hazard ratio (HR) was 0.496 (95% CI, 0.235 to 1.043) for time to stroke-related event for interferon ß-1a, at any dose.
In patients receiving interferon-β1a 44 µg dosed 3 times weekly versus placebo, the incidence rate ratio was 0.436 (95% CI, 0.190 to 0.998). Among patients given interferon ß-1a that were treated for <2 years, the incidence rate ratio was 0.602 (95% CI, 0.159 to 2.277). For those treated for ≥2 years, it was 0.469 (95% CI, 0.196 to 1.124).
Data from Merck’s (EMD Serono) safety database included 2039 adverse events, of which 21% (n = 421) were medically confirmed. In total, 66% (n = 1345) were deemed serious, with 28% (n = 375)of these being medically confirmed. The overall reporting rate for stroke was 13.286 per 10,000 patient-years.
The most frequently reported event in line with stroke, in those receiving interferon β-1a, was hemiparesis (n = 893). Of these adverse events, 230 were classed as serious and 54 of these were medically confirmed (23.5%). The remaining 663 were non-serious, of which 46 were medically confirmed (7%).
These findings were in direct contrast with a 2017 nested case-control evaluation of the safety of the therapy based on a real-world population which showed a 1.8-fold increased risk of stroke associated with interferon ß-1a.3 Venkatesh and colleagues noted that this may be explained partially by potential selection bias in the controlled trials towards, with them leaning toward “healthier” patients.
“However, it is important to note that the present study includes patients with different severities of MS,” they wrote. “The nested case-control study is based on data from a claims database and it should be noted that this type of analysis is subject to limitations when compared with data from randomized controlled trials.”
1. Sabidó M, Venkatesh S, Hayward B, Aldridge J, Gillet A. Subcutaneous interferon-β1a does not increase the risk of stroke in patients with multiple sclerosis: analysis of pooled clinical trials and post-marketing surveillance. Adv Ther. epub September 25, 2018. doi: 10.1007/s12325-018-0790-1.
2. Allen NB, Lichtman JH, Cohen HW, Fang J, Brass LM, Alderman MH. Vascular disease among hospitalized multiple sclerosis patients. Neuroepidemiology. 2008;30(4):234-8. doi: 10.1159/000128103.
3. de Jong HJI, Kingwell E, Shirani A, et al. Evaluating the safety of β-interferons in MS: A series of nested case-control studies. Neurology. 2017;88(24):2310-2320. doi: 10.1212/WNL.0000000000004037.