Aim of the study: To evaluate the long-term retention rate, efficacy, and tolerability of adjunctive cenobamate (CNB) in patients with drug-resistant epilepsy within the Polish Expanded Access Programme (EAP).
Clinical rationale for the study: Long-term retention rate is a useful measure of effectiveness including efficacy, safety, and tolerability of antiseizure medications.
Material and methods: We conducted a multicentre retrospective analysis of consecutive patients with focal epilepsy treated with CNB in the EAP between January 2020 and May 2023. All patients who completed the open-label extension phases of the YKP3089C013 and YKP3089C017 trials were offered the opportunity to continue CNB treatment within the EAP. We analysed cenobamate retention, seizure outcomes, and adverse events.
Results: 38 patients (18 females; 47.3%) continued CNB treatment within the Expanded Access Programme for 41 months. The mean baseline age of patients was 39.3 years (range: 18-57). All patients were on polytherapy, with the most commonly used antiseizure medications being valproate, levetiracetam, and carbamazepine. Adjunctive CNB treatment resulted in a reduced mean seizure frequency from 8.1 seizures (range: 4-20) per month to 3 seizures (range: 0-8) per month. At the final follow-up, the median CNB dose was 200 mg/day (range: 50-350). Among the patients, 24 (63.1%) achieved ≥ 50% seizure reduction, and eight (21%) remained seizure-free for at least 12 months. One in three patients experienced adverse events, which resolved in half of the subjects. The most frequent adverse events were dizziness, somnolence, and headache. The retention rate after completing the open-label extension phase was 100%.
Conclusions and clinical implications: Long-term effectiveness, including ≥ 50% seizure reduction and a 100% retention rate, was sustained over 41 months of CNB treatment within the Expanded Access Programme. No new safety issues were identified. These results provide support for the potential long-term clinical benefits of cenobamate.
Keywords: adverse events; cenobamate; efficacy; retention rate; safety.