Incidence and determinants of seizures in multiple sclerosis: a meta-analysis of randomised clinical trials.

BACKGROUND

Seizures are reported to be more prevalent in individuals with multiple sclerosis (MS) compared with the general population. Existing data predominantly originate from population-based studies, which introduce variability in methodologies and are vulnerable to selection and reporting biases.

METHODS

This meta-analysis aims to assess the incidence of seizures in patients participating in randomised clinical trials and to identify potential contributing factors. Data were extracted from 60 articles published from 1993 to 2022. The pooled effect size, representing the incidence rate of seizure events, was estimated using a random-effect model. Metaregression was employed to explore factors influencing the pooled effect size.

RESULTS

The meta-analysis included data from 53 535 patients and 120 seizure events in a median follow-up of 2 years. The pooled incidence rate of seizures was 68.0 per 100 000 patient-years, significantly higher than the general population rate of 34.6. Generalised tonic-clonic seizures were the most common type reported, although there was a high risk of misclassification for focal seizures with secondary generalisation. Disease progression, longer disease duration, higher disability levels and lower brain volume were associated with a higher incidence of seizures. Particularly, sphingosine-1-phosphate receptor (S1PR) modulators exhibited a 2.45-fold increased risk of seizures compared with placebo or comparators, with a risk difference of 20.5 events per 100 000 patient-years.

CONCLUSIONS

Patients with MS face a nearly twofold higher seizure risk compared with the general population. This risk appears to be associated not only with disease burden but also with S1PR modulators. Our findings underscore epilepsy as a significant comorbidity in MS and emphasise the necessity for further research into its triggers, preventive measures and treatment strategies.

Informations de copyright

© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: Potential conflicts of interest: nothing to report relevant to the present study. Financial disclosures: VP: no conflicts of interests. SH: travel funding and/or speaker honoraria from Biogen, CSL Behring, Novartis, Roche and Sanofi. MDF: advisory boards and steering committees for and received speaker or writing honoraria, research support and funding for travelling from Alexion, Bristol-Mayer Squibb, Bayer, Biogen, Horizon, Janssen, Merck, Mylan, Novartis, Roche, Sanofi, Siemens Healthineers, Teva and Viatris. FC: travel grants and/or speaking honoraria from Biogen, Merck, Roche and Sanofi and research grants from Merck. VDL: no conflicts of interests. CT: honoraria for speaking and travel grants from Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi and Teva. CG: honoraria for speaking and travel grants from Biogen, Merck, Novartis, Roche, Sanofi, Teva and Viatris. LP: personal fees and non-financial support from Biogen, Bristol-Mayer Squibb, Merck, Novartis, Roche, Sanofi and Viatris.