Abstracts

Rationale: Cenobamate (CNB) is a highly efficacious newer anti-seizure medication (ASM) that was approved in 2019 for the treatment of focal onset seizures in adults. Approval of ASMs for pediatric use traditionally lags by several years, leading to frequent off-label use of ASMs for children. CNB is increasingly used to treat children with drug-resistant epilepsy. The largest pediatric cohort in whom the efficacy and tolerability of CNB has been described includes 21 patients—the majority in their adolescence. The safety profile and efficacy of CNB merit further characterization in a larger cohort of pediatric patients and in younger children. This retrospective study aims to evaluate the efficacy and describe the tolerability of CNB in a larger cohort of pediatric patients.


Methods: Patients who started CNB at Cincinnati Children’s Hospital Medical Center between November 2019 and June 2023 were included in the study. Safety analyses included patients who took at least 1 dose of CNB. Efficacy analyses excluded patients who took CNB for less than 1 month at the end of the study period. Patients were censored if they started a new ASM, underwent surgery, started neuromodulation, or started dietary therapy during the follow-up period. Safety and efficacy were analyzed at 3, 6, and 12 months after CNB initiation.


Results: 123 patients between 2 to 39 years of age (mean 17.8 ± 7.1) started CNB; 59 patients were < 18 years old. On average, patients had tried 5.8 ± 3.7 prior ASMs and were concurrently on 2.6 ± 0.9 ASMs. 60% of patients (74/123) reported adverse events (AEs) that were attributed to CNB by either the treating provider or caregiver. The most common AEs were somnolence (48%), ataxia (16%), behavioral issues (12%), and weight loss (10%). Of note, there was 1 fatality, unrelated to CNB. 16 patients discontinued CNB during follow-up, including 1 patient with suicidal ideation attributed to CNB. In patients with focal seizures (n=96), a significant reduction in seizure burden was seen at 3, 6, and 12 months after CNB initiation. In patients with generalized seizures (n=47, includes bilateral tonic clonic, tonic, myoclonic, atonic, and absence), significant reduction was seen at 6 months.


Conclusions: Most patients taking CNB experienced AEs but discontinuation of therapy was uncommon, suggesting AEs were mostly tolerable. Serious AEs were quite rare but warning patients about possible suicidal ideation and prompt discontinuation is important. CNB was effective in reducing the frequency of focal seizures at all timepoints. For generalized seizures, a significant effect was seen only at the 6-month timepoint. A larger sample of patients with generalized epilepsy needs to be evaluated, and the possible impact of etiology and syndromic diagnoses needs to be explored. CNB may be more useful for a subset of generalized seizure types; further exploration and subcategorization is warranted. Overall, CNB demonstrates promising potential for pediatric and young adult patients with refractory epilepsy.


Funding: None