Freedon study: Real‐life outcomes of cenobamate in different lines of treatment

OBJECTIVES: Cenobamate is an antiseizure medication (ASM) with proven effectiveness in individuals with highly refractory epilepsy. This study investigated the effectiveness and tolerability of cenobamate in different treatment lines and a less refractory setting. METHODS: This was a multicenter, retrospective, observational study. Adults with focal epilepsy, 2-6 prior ASMs, and ≥12 months between cenobamate initiation and database closure were included. Data from patients' charts were collected and included in the Drug-Resistant Epilepsy Registry of the Spanish Epilepsy Society using Research Electronic Data Capture. Primary effectiveness endpoints included changes in seizure frequency at 3, 6, and 12 months after cenobamate initiation according to different treatment lines. Primary safety endpoints included the percentage of patients with adverse events (AEs). RESULTS: In total, 486 patients were included (mean age 42.8 years). The mean number of prior ASMs was 4.4 (2-6); the mean number of concomitant ASMs at cenobamate initiation was 2.5 (1-5). At 12 months, treatment retention was 92% and median dose was 200 mg. One-year seizure-freedom rates were 32.5%, 33.3%, 21.4%, 24.2%, and 11.4% in those treated with 2-6 prior ASMs, respectively. The proportions of patients achieving ≥50%, ≥75%, ≥90%, and 100% reductions in seizure frequency at 12 months were significantly higher in patients with 2-3 (earlier treatment lines) vs 4-6 prior ASMs (later treatment lines; p ≤ .004). Improvements in seizure severity were reported in 71.9% of patients during follow-up (82.5% and 62.1% in those with 2 and 6 prior ASMs, respectively). At 12 months, 56.4% of patients had reported AEs, with somnolence the most frequent, and 4.9% had AEs requiring cenobamate discontinuation. SIGNIFICANCE: Cenobamate was effective and well tolerated in patients who had tried 2-6 prior ASMs in a real-world setting. High effectiveness was confirmed at 1 year, with better outcomes in earlier users.