Abstract
Objective There is a two to three-fold increased prevalence of seizures in multiple sclerosis (MS) patients compared to the general population. Conflicting reports exist of seizures occurring as an adverse event in disease modifying therapies (DMTs) such as interferon, glatiramer acetate, and fingolimod; however, DMTs have also been postulated to have anti-epileptogenic effects. We aimed to evaluate the risk of seizures in MS patients on DMTs compared to placebo.
Methods MEDLINE (OVID), EMBASE, CINAHL, and ClinicalTrials.gov were searched to 21st August 2021. Two reviewers independently screened and extracted data from full-text papers for placebo-controlled randomised trials of DMT(s) as monotherapy in patients ≥18 years and appraised the risk of bias. The primary outcome was seizure risk ratio (SRR) in dose-pooled DMT-treated patients compared to placebo. Meta-analyses and network meta-analyses (NMA) were performed using ‘R’.
Results 331 of 1509 screened studies underwent full-text eligibility review. 56 studies were included, comprising 29,388 patients randomised to placebo (n=10,479) or DMT (n=18,909). 60 seizures were reported (DMT = 41, placebo = 19). Notably, 12 seizures occurred in one trial in patients treated with siponimod 2mg daily, corresponding to 1 seizure in 276.25 patient-exposed-years; no seizures were reported in other siponimod studies. Preliminarily, meta-analyses and NMA did not demonstrate a difference in SRR between DMT and placebo, nor increased SRR according to specific DMT.
Conclusion DMT use is not associated with increased seizure risk in MS patients, which can be incorporated in the counselling of patients commencing DMTs.
