Real-world experience with cenobamate: A systematic review and meta-analysis

•Treatment response was achieved in about two-thirds (68 %) of patients with DRE, and seizure freedom in 16.2 %.•Cenobamate was taken with a high retention rate and discontinued predominantly due to a lack of efficacy.•More than 50 % of patients showed adverse effects requiring dose adjustment of concomitant anti-seizure medication. Despite many new ASM, the rate of patients with drug-resistant epilepsy (DRE) has not changed. Cenobamate (CNB) is a novel ASM for the treatment of focal-onset seizures in adults with high seizure freedom rates in randomized controlled trials (RCT). Although CNB appears to be effective, it is not commonly prescribed to patients with DRE, resulting in a lack of “real-world data”. To evaluate the real-world effect of CNB and to assess the generalizability of RCT data, a systematic review and meta-analysis was conducted. Pooled proportions were calculated using a random intercept logistic regression model. The analysis included seven studies with a total of 229 patients with DRE, 77.3 % of whom were adults and 91.5 % had focal-onset seizures. Seizure reduction >50 % was achieved in 68 % of patients [54.54; 79.07], with seizure freedom in 16.2 % [8.38; 28.97]. There was no difference between pediatric and adult patients. CNB was discontinued in 10 % [6.74; 14.6] of patients, mostly due to lack of efficacy (39 %) or adverse effects (AE, 43 %). AE, observed in 57.3 % [39.7; 73.2] of patients, included fatigue and vertigo. A comparison of the rates calculated in this meta-analysis to the active arm of equivalent RCTs revealed no significant difference. CNB achieves a good treatment response in patients with DRE in real-world settings, like the effect reported in RCTs. The high heterogeneity between studies calls for studies focusing on specific DRE subpopulations.