A multicenter cohort study on the efficacy, retention, and tolerability of cenobamate in patients with developmental and epileptic encephalopathies.

Objective: This study was undertaken to evaluate retention and treatment characteristics of cenobamate (CNB) in patients with developmental and epileptic encephalopathies (DEEs) in clinical practice.

Methods: This multicenter, retrospective cohort study recruited all patients with DEEs who started CNB treatment between October 2020 and April 2023 at participating epilepsy centers.

Results: A total of 41 patients (mean age = 28.3 ± 13.1 years, median = 26 years, range = 4-73 years; 24 male [58.5%]) were treated with CNB. Of these, 33 had Lennox-Gastaut syndrome, seven had tuberous sclerosis complex, and one had Dravet syndrome. The median number of antiseizure medications (ASMs) at enrollment was three, and patients had a median of eight failed ASMs in the past. The retention rate for CNB was 94.9% at 3 months, 82.9% at 6 months, and 72.4% at 12 months of follow-up. Cumulative exposure to CNB was 477 months (39.2 years). Efficacy (50% responder rate) at 3 months was 39% including 7.3% seizure-free patients. Long-term, the 50% responder rate at 12 months was 34.5% (seizure-free [10.3%]). There was no difference in response at 3 months regarding sex, age (adult vs. children), previous and concomitant number of ASMs, or first target dose of CNB. Treatment-emergent adverse events were predominantly sedation and dizziness and were observed in 58.5% of patients. Children and adolescents showed comparable efficacy, retention, and tolerability compared to adults.

Significance: The findings from this open-label, retrospective study suggest that CNB may be effective in some patients with DEEs. Its overall use in DEEs seems to be safe and well tolerated. We observed similar response, retention, and adverse event profiles in children and adults.