Add‐on treatment with cenobamate is already effective at low doses in refractory focal epilepsy: A prospective observational study

Abstract

AbstractObjectiveCenobamate, a novel antiseizure medication with a dual mechanism of action, has been shown in pivotal trials to significantly improve seizure control in treatment‐resistant focal epilepsy. We aimed to evaluate whether these promising results could be confirmed in a real‐world setting with a follow‐up period of up to 12 months.MethodsPatients from a tertiary epilepsy center who received cenobamate add‐on between June 2021 and October 2023 were followed up prospectively at 3, 6, and 12 months after treatment initiation for assessment of seizure outcomes and treatment‐related adverse events.ResultsThe clinical cohort included 112 adult patients with 30% nonlesional cases and a wide spectrum of epileptogenic lesions underlying refractory focal epilepsy. We observed a significant reduction in monthly seizure frequency of all seizure types already after 3 months of treatment at a median cenobamate dose of 100 mg/day. Forty‐six percent of patients were responders with a ≥50% seizure reduction, 26% had a ≥75% seizure reduction, and 9% became seizure‐free. Among the 74 patients with available follow‐up of 12 months, the responder rates reached 55%, 35%, and 19% for ≥50%, ≥75%, and 100% seizure reduction, respectively. After 3 months of treatment, 38% of patients reported adverse effects, mainly (84%) mild to moderate in intensity. Adjustment of comedication allowed successful management of adverse effects in 32% of patients. At a group level, there was no correlation between the cenobamate daily dose and the incidence of adverse events.SignificanceWe found a clinically relevant response to cenobamate already at a low daily dose of 100 mg also in a patient cohort with a higher degree of drug resistance than in pivotal trials. Our prospectively collected data provide real‐world evidence for high efficacy and good tolerability of the drug, although no standardized treatment protocol or comparison with a control group was applied.