Efficacy and safety of add‐on antiseizure medications for focal epilepsy: A network meta‐analysis

Abstract

Abstract Objective Several antiseizure medications (ASMs) have been approved for the treatment of focal epilepsy. However, there is a paucity of evidence on direct comparison of ASMs. We evaluated the comparative efficacy and safety of all approved add‐on ASMs for the treatment of focal epilepsy using network meta‐analysis. Methods Data through extensive literature search was retrieved from PubMed, Embase, Cochrane, and ClinicalTrial.gov databases using predefined search terms from inception through March 2023. PRISMA reporting guidelines (CRD42023403450) were followed in this study. Efficacy outcomes assessed were ≥50%, ≥75%, and 100% responder rates. Patient retention rate and safety outcomes such as overall treatment‐emergent adverse events (TEAEs) and individual TEAEs were assessed. “Gemtc” 4.0.4 package was used to perform Bayesian analysis. Outcomes are reported as relative risks (RRs) and 95% confidence interval (CI). Results Literature search retrieved 5807 studies of which, 75 studies were included in the analysis. All ASMs showed significantly higher ≥50% responder rate compared with placebo. Except the ≥75% seizure frequency reduction for zonisamide (2.23; 95% CI: 1.00–5.70) and 100% for rufinamide (2.03; 95% CI: 0.54–11.00), all other interventions showed significantly higher ≥75% and 100% responder rates compared with placebo. Among treatments, significantly higher 100% responder rate was observed with cenobamate compared to eslicarbazepine (10.71; 95% CI: 1.56–323.9) and zonisamide (10.63; 95% CI: 1.37–261.2). All ASMs showed a lower patient retention rate compared to placebo, with the least significant value observed for oxcarbazepine (0.77; 95% CI: 0.7–0.84). Levetiracetam showed a lower risk of incidence (1.0; 95%CI: 0.94–1.1; SUCRA: 0.885067) for overall TEAE compared with other medications. Significance All approved ASMs were effective as add‐on treatment for focal epilepsy. Of the ASMs included, cenobamate had the greatest likelihood of allowing patients to attain seizure freedom. Plain Language Summary This article compares the efficacy and safety of antiseizure medications (ASMs) currently available to neurologists in the treatment of epileptic patients. Several newer generation ASMs that have been developed may be as effective or better than the older medications. We included 75 studies in the analysis. In comparison, all drugs improved ≥50%, ≥75% and 100% responder rates compared to control, except for Zonisamide and Rufinamide in the ≥75% and 100% responder rate categories. Retention of patients undergoing treatment was lower in drugs than placebo. All drugs were tolerated, the levetiracetam showed the best tolerability. Cenobamate more likely help completely to reduce seizures.

Keywords

• add‐on therapy
• antiseizure medication
• focal epilepsy
• network meta‐analysis