Background and Disease Burden
Drug-resistant focal epilepsy remains a significant clinical challenge, affecting approximately 30% of epilepsy patients despite treatment with standard antiseizure medications (ASMs). The condition is associated with increased morbidity, mortality, and reduced quality of life. This study addresses a critical gap in clinical decision-making by providing direct comparative effectiveness data among newer ASMs.
Study Design
This multicenter pooled analysis included 1,949 adult patients (median age 42 years) from 71 epilepsy centers who received adjunctive therapy with brivaracetam, cenobamate, lacosamide, or perampanel. The primary outcome was responder rate at 6 months (≥50% seizure reduction). Secondary outcomes included 12-month responder rate, seizure freedom duration, and medication retention.
Key Findings
Cenobamate demonstrated superior effectiveness across all outcomes. At 6 months, cenobamate had significantly higher odds of 50% seizure reduction compared to brivaracetam (OR 0.18), perampanel (OR 0.26), and lacosamide (OR 0.29). This superiority was maintained at 12-month follow-up. While cenobamate showed the highest adverse effect rate (57.8%), it also demonstrated the best 12-month retention rates compared to other ASMs.
Expert Commentary
These findings provide compelling real-world evidence supporting cenobamate as a preferred adjunctive therapy for drug-resistant focal epilepsy. The study’s large patient population enhances generalizability, though potential confounding factors and variable cenobamate dosing merit consideration in clinical application.
Conclusion
The CREW study establishes cenobamate’s superior effectiveness in real-world practice, potentially reshaping treatment algorithms for drug-resistant focal epilepsy. These results warrant consideration in future clinical guidelines while highlighting the need for continued comparative effectiveness research.