Cenobamate as add-on treatment in ultra-refractory focal epilepsy: Real-world results from The Danish Epilepsy Centre, Dianalund, Denmark

OBJECTIVES: At The Danish Epilepsy Centre, Dianalund, Denmark, we aimed to assess the long-term efficacy, tolerability profile, and influence on concomitant antiseizure medications (ASMs) of cenobamate as an add-on treatment in patients with ultra-refractory focal epilepsies.

METHODS: Adult patients with ultra-refractory epilepsy (defined as focal epilepsies in which ≥ 6 treatments, including ASM trials, epilepsy surgery, and vagus nerve stimulator, failed to achieve seizure control) treated with add-on cenobamate between October 2021 and June 2024 were included in our retrospective, observational study. Data were collected through electronic patient records and seizure-diaries.

RESULTS: 32 patients were included. The mean length of treatment was 21 months (range 2-32 months) and the median dose of cenobamate was 250 mg (range 50-400 mg). Fourteen/32 (44%) patients were responders (≥ 50% reduction in seizure frequency) to cenobamate, including five patients who became seizure-free (15.6% of the total cohort). Eleven/32 (34%) discontinued due to adverse effects (AEs) or lack of efficacy. Patients with active focal-to-bilateral-tonic-clonic seizures remaining on treatment decreased by 50%. The ASM most frequently reduced was lacosamide, while the one most often discontinued was lamotrigine. Fifteen/32 (47%) patients reported at least one AE during the treatment period of 32 months. Two-thirds were resolved by dose-reduction of ASMs or cenobamate. AEs most frequently reported were tiredness and dizziness; the lowest incidence of these AE was found when cenobamate was added as the third drug.

SIGNIFICANCE: Our study underlines the usefulness of cenobamate in treating patients with ultra-refractory epilepsy and indicates its long-term effectiveness in real-world clinical practice.