Abstracts

Rationale: Epilepsy affects many patients who do not respond to initial antiseizure medications. Despite additional medications, some patients remain refractory. Cenobamate (CNB), approved in May 2020, shows promising trial results but raises concerns about long-term efficacy outside controlled settings. CNB is indicated for focal seizures in adults. Its efficacy was established in two randomized, double-blind trials, later supported by an open-label extension study. This study evaluates the real-world effectiveness, safety, and tolerability of adjunctive CNB therapy in drug-resistant epilepsy over an extended follow-up. By comparing our findings with prior controlled and OLE studies, we provide insights into CNB's real-world use, focusing on reasons for CNB failure.

Methods: This retrospective, observational study was conducted at the University of California, Davis, Epilepsy clinic by retrospective analysis of clinical records. It included patients aged ≥18 years who started CNB after May 2020.

Results: A study of 54 patients with medically refractory epilepsy (median age 41.5 years, 55.56% male, 44.44% female) found that 75.93% had focal epilepsy, 12.96% generalized, 9.26% unknown, and 1.85% syndrome, with a median epilepsy duration of 23.28 years and baseline seizure frequency of about 6.5/month. The median number of prior antiseizure medications (ASMs) was 4, decreasing to 2 after incorporating CNB. CNB failed in 44% of patients, with a median use duration of 7.5 months and a median dose of 150 mg at failure. Retention rates were 88.9% at 3 months, 81.5% at 6 months, 70.4% at 12 months, and 59.3% at 24 months. Among non-failures, responder rates were 29.17% (≥90% reduction), 35.42% (≥75% reduction), and 52.08% (≥50% reduction), with a median reduction rate of 50.0%. Seizure freedom was achieved in 12% of all patients and 6% of those who failed. CNB failure was due to incomplete efficacy (38.10%), adverse effects (38.10%), both (9.52%), and other reasons (4.76%). Common adverse effects included fatigue (17%), somnolence (12%), dizziness (12%), and imbalance (12%).

Conclusions: This study highlights the importance of real-world CNB data to complement controlled trials and OLE studies. Despite promising trial results, our findings show complexities in real-world settings. CNB significantly reduces seizure frequency, with high retention rates at 3, 6, 12, and 24 months, indicating sustained benefits. However, nearly half of the patients discontinued CNB due to incomplete efficacy or adverse effects, emphasizing the need for careful patient selection and monitoring, particularly with patients who are on multiple sodium channel blockers. Understanding CNB failures can help clinicians optimize therapy for drug-resistant epilepsy.
References:
Klein P, Aboumatar S, Brandt C, Dong F, Krauss GL, Mizne S, Sánchez-Álvarez JC, Steinhoff BJ, Villanueva V. Long-term Efficacy and Safety From an Open-Label Extension of Adjunctive Cenobamate in Patients With Uncontrolled Focal Seizures. Neurology. 2022 Sep 5;99(10). doi: 10.1212/WNL.0000000000200792. PMID: 35705501; PMCID: PMC9519254.


Funding: None