ConexiantCenobamate Shows Stronger Real-World Seizure Control

The CREW study pooled real-world data from 71 epilepsy centers and nearly 2,000 patients with drug-resistant focal epilepsy, finding cenobamate delivered significantly higher seizure response and freedom versus brivaracetam, lacosamide, and perampanel at both 6 and 12 months. The advantage held even though cenobamate patients had more refractory disease at baseline.

Clinical Considerations

• Cenobamate’s efficacy advantage persisted after adjusting for baseline seizure burden and prior treatment exposure, strengthening the real-world signal beyond unadjusted results.
• Somnolence, dizziness, and CNS symptoms were the most common adverse effects, occurring in 57.8% of cenobamate patients, the highest rate among all four agents.
• Despite its adverse effect burden, cenobamate retention outpaced brivaracetam and perampanel at 12 months, suggesting patients continued therapy even with side effects.
• Lacosamide carried the lowest adverse effect rate at 14.8%, remaining a viable option when tolerability drives sequencing decisions.

Practice Applications

• Prioritize cenobamate earlier in adjunctive sequencing for drug-resistant focal epilepsy when efficacy is the primary goal.
• Counsel patients on somnolence and dizziness before cenobamate initiation, particularly during titration.
• Consider lacosamide when comorbidities or polypharmacy make tolerability the deciding factor.
• Track seizure frequency at 6 months to evaluate responder status and inform continuation decisions.

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