Efficacy and safety of cenobamate in the treatment of drug-resistant epilepsy: a systematic review and meta-analysis in adult, pediatric, and combined populations.

完整摘要 · 英文原文

OBJECTIVES: Cenobamate (CNB), a next-generation anti-seizure medication approved by the US Food and Drug Administration (FDA) in 2019, offers a new treatment option for adult with focal-onset seizures. However, clinical experience with CNB in children remains limited, as do comparative analyses of its efficacy between children and adults. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of CNB for treating drug-resistant epilepsy (DRE) across both age groups. METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library for studies published from inception to May 2026. Data were analyzed using RStudio with the meta, metafor, and dplyr packages. A random-effects model was used for all pooled estimates because substantial heterogeneity was anticipated and observed. Risk of bias in randomized controlled trials (RCTs) was assessed using the Cochrane Risk of Bias 2.0 tool, while the ROBINS-I (Risk Of Bias In Non-randomized Studies of Interventions) tool was used for retrospective, non-randomized studies. RESULTS: After duplicate removal, 304 records were identified. Based on prespecified inclusion and exclusion criteria, 36 studies (36 reports: 35 full-text articles and 1 conference abstract) were included in the final analysis. Of these, 22 studies comprised 6,256 adults with epilepsy, 6 studies included 256 pediatric patients, and 8 mixed-age studies involving 451 patients did not provide separable age-specific data; these studies were therefore included only in the overall (all-age) analysis and were not included in the adult or pediatric subgroup analyses. In adults, the pooled responder proportion (≥ 50% seizure reduction) was 0.65 (21 studies, 3,871 patients; 95% CI: 0.58-0.71), the seizure freedom rate was 0.15 (21 studies, 3,963 patients; 95% CI: 0.10-0.21), the incidence of adverse events (AEs) was 0.63 (17 studies, 3,611 patients; 95% CI: 0.51-0.74), and the incidence of serious adverse events (SAEs) was 0.00 (19 studies, 3,487 patients; 95% CI: 0.00-0.02). In pediatric patients, the preliminary response rate was 0.60 (6 studies, 256 patients; 95% CI: 0.39-0.78), the preliminary seizure freedom rate was 0.20 (4 studies, 212 patients; 95% CI: 0.15-0.26), the preliminary incidence of AEs was 0.48 (5 studies, 236 patients; 95% CI: 0.42-0.55), and the preliminary incidence of SAEs was 0.03 (4 studies, 63 patients; 95% CI: 0.01-0.12). These estimates were numerically similar to those observed in adults. In the overall analysis (all patients combined), the response rate was 0.63 (35 studies, 4,578 patients; 95% CI: 0.58-0.68), the seizure freedom rate was 0.15 (32 studies, 4,392 patients; 95% CI: 0.11-0.19), the incidence of AEs was 0.62 (29 studies, 4,253 patients; 95% CI: 0.53-0.69), and the incidence of SAEs was 0.00 (30 studies, 3,767 patients; 95% CI: 0.00-0.02). CONCLUSION: In summary, this is the first comprehensive meta-analysis to evaluate the efficacy and safety of CNB across pediatric, adult, and combined populations. Although pediatric point estimates were numerically similar to adult estimates, these findings are derived from indirect subgroup comparisons and should be interpreted cautiously. Most included studies were retrospective observational studies with notably small pediatric samples, inherently limiting the strength of evidence in children. Therefore, further prospective studies are warranted to better investigate the efficacy and safety of CNB specifically in pediatric patients.