Real-World Use of Cenobamate in Paediatric Drug-Resistant Epilepsy: Long-Term Efficacy, Safety, and Co-Medication...

We evaluated the real-world efficacy, tolerability, treatment retention, and quality-of-life effects of cenobamate in paediatric drug-resistant epilepsy.

We retrospectively studied 78 paediatric patients with drug-resistant epilepsy treated with cenobamate for ≥ 3 months at a tertiary epilepsy centre. We assessed seizure frequency, adverse effects, cognitive/behavioural outcomes, and changes in concomitant antiseizure medications. The primary efficacy endpoint was a ≥ 50% reduction in seizure frequency. We assessed safety through reported adverse events and clinical improvement using the Clinical Global Impression-Improvement (CGI-I) scale. We used Kaplan-Meier analyses to assess responder rates and treatment retention over 18 months.

A ≥ 50% seizure reduction was achieved in 67.9% of patients including 6.4% who became seizure-free. Polytherapy was simplified in 38% overall and in 56.6% of responders. Adverse events occurred in 43.6% of patients, were mostly mild, and led to discontinuation in only one patient (1.3%). CGI-I indicated clinical improvement in 24.4%. Kaplan-Meier analysis showed sustained response in 93% of initial responders at 18 months. Treatment retention remained high: 94.7% at 3 months, 89.6% at 12 months, and 86.8% at 18 months. Median follow-up was 12 months (range 3-18), with 60.3% followed for ≥ 12 months and 41% for the full 18 months.

Our study confirms and extends recent evidence on the efficacy and favourable tolerability of cenobamate in paediatric drug-resistant epilepsy. We observed functional improvements and polytherapy simplification, suggesting broader therapeutic benefits. These findings warrant prospective validation in specific paediatric epilepsy syndromes and may help support regulatory approval for paediatric use.