Real-world safety and effectiveness of cenobamate in patients with focal onset seizures: outcomes from an Expanded Access Program
Vicente Villanueva 1 , Daniel Santos-Carrasco 2 3 , Pablo Cabezudo-García 4 , Asier Gómez-Ibáñez 5 , Mercedes Garcés 1 , Pedro Serrano-Castro 4 , Maria D Castro-Vilanova 6 , Débora Sayas 1 , Francisco J Lopez-Gonzalez 7 , Xiana Rodríguez-Osorio 7 , Gustavo Torres-Gaona 8 , Rosa A Saiz-Diaz 9 , Kevin G Hampel 1 , Meritxell Martinez-Ferri 10 , Maria J Aguilar-Amat 11 , Blanca Mercedes-Alvarez 12 , Vanessa García-Morales 13 , Ana Del Villar-Igea 14 , Andreu Massot-Tarrús 10 , Juan J Rodríguez-Uranga 2
Objective: This study investigated early, real-world outcomes with cenobamate (CNB) in a large series of patients with highly drug-resistant epilepsy within a Spanish Expanded Access Program (EAP).
Method: This was a multicentre, retrospective, observational study in 14 hospitals. Inclusion criteria were age ≥18 years, focal seizures and EAP authorization. Data were sourced from patient clinical records. Primary effectiveness endpoints included reductions (100%, ≥90%, ≥75%, ≥50%) or worsening in seizure frequency at 3-, 6- and 12-month visits and at the last visit. Safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation.
Results: The study included 170 patients. At baseline, median epilepsy duration was 26 years and median number of seizures/month was 11.3. The median number of prior antiseizure medications (ASMs) and concomitant ASMs were 12 and 3, respectively. Mean CNB dosages/day were 176 mg, 200 mg and 250 mg at 3, 6 and 12 months. Retention rates were 98.2%, 94.5% and 87% at 3, 6 and 12 months. At last available visit, the rate of seizure-freedom was 13.3%; ≥90%, ≥75% and ≥50% responder rates were 27.9%, 45.5% and 63%, respectively. There was a significant reduction in the number of seizures per month (mean 44.6%; median 66.7%) between baseline and the last visit (p<0.001). Responses were maintained regardless of the number of prior or concomitant ASMs. The number of concomitant ASMs was reduced in 44.7% of patients. The cumulative percentage of patients with AEs and AEs leading to discontinuation were 68.2% and 3.5% at 3 months, 74.1% and 4.1% at 6 months, and 74.1% and 4.1% at 12 months. The most frequent AEs were somnolence and dizziness.
Significance: In this highly refractory population, CNB showed a high response regardless of prior and concomitant ASMs. AEs were frequent but mostly mild-to-moderate, and few led to discontinuation.
CITATION Epilepsia Open. 2023 May 7. doi: 10.1002/epi4.12757