February 17, 2023

Adjunctive Cenobamate (XCOPRI ®) in Highly Active and Ultra-Refractory Focal Epilepsy: A ‘Real-World’ Retrospective Study

Abstract found on Wiley Online Library

Objective: Recent clinical trials showed that cenobamate substantially improves seizure control in focal-onset drug-resistant epilepsy. However, little is known about cenobamate’s performance in highly active (?20 seizures/month) and ultra-refractory focal epilepsy (?6 failed epilepsy treatments, including anti-seizure medications [ASM], epilepsy surgery and vagus nerve stimulation). Here, we studied cenobamate’s efficacy and tolerability in a ‘real-world’ severe DRE cohort.

Methods: We conducted a single-centre retrospective analysis of consecutive adults treated with cenobamate between October 2020 and September 2022. All patients received cenobamate through an Early Access Program. Cenobamate retention, seizure outcomes, treatment-emergent adverse events, and adjustments to concomitant ASMs were analysed.

Results: Fifty-seven patients received cenobamate for at least three months (median duration, 11 months). The median cenobamate dose was 250mg/day (range 75-350mg). Baseline demographics were consistent with highly active (median seizure frequency, 60/month) and ultra-refractory epilepsy (median previously failed ASMs, nine). Most (87.8%) had prior epilepsy surgery and/or vagus nerve stimulation. Six patients stopped cenobamate due to lack of efficacy and/or adverse events. One patient died from factors unrelated to cenobamate. Among patients who continued cenobamate, three achieved seizure freedom (5.3% of cohort), 24 had a 75-99% reduction in seizures (42.1% of cohort), and 16 had a 50-74% reduction (28.1% of cohort). Cenobamate led to abolition of focal to bilateral tonic-clonic seizures in 55.6% (20/36) of patients. Among treatment responders, 67.4% (29/43) were treated with cenobamate doses of ?250mg/day. Three-quarters of patients reported at least one side-effect, most commonly fatigue and somnolence. Adverse events most commonly emerged at cenobamate doses of ?250mg/day. Side-effects were partially manageable by reducing the overall ASM burden, most often clobazam, eslicarbazepine and perampanel.

Significance: Patients with highly active and ultra-refractory focal epilepsy experienced meaningful seizure outcomes on cenobamate. Emergence of adverse events at doses above 250mg/day may limit the potential for further improvements in seizure control at higher cenobamate doses.