ArticleNeurology and therapy2026
Early Cenobamate as a Third-Line Option in Drug-Resistant Focal Epilepsy: A Paradigm Shift?
Article in Neurology and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionDrug-resistant epilepsy (DRE) affects nearly 30% of patients with epilepsy, and the optimal sequencing of adjunctive anti-seizure medications (ASMs) remains uncertain. Comparative real-world evidence on early use of newer ASM is limited. This study explores real-world comparative effectiveness, safety and 12-month retention of cenobamate (CNB) introduced as early third-line adjunctive therapy compared with perampanel (PER) and brivaracetam (BRV) in adults with focal-onset DRE.
methodsThis multicenter observational study included 34 CNB patients and 37 matched controls treated with PER or BRV, all after failure of two prior ASMs. Primary outcome was 12-month treatment retention; secondary outcomes included responder rates (≥ 50%, ≥ 75%, 100%) and adverse events at 3, 6 and 12 months. Comparative analyses were exploratory. Univariate analyses and longitudinal generalized linear mixed-effects models (GLMMs) were used to describe outcome trajectories over time.
resultsCNB showed a 12-month retention rate of 94.1%. Descriptively, seizure freedom was achieved in 62.5% of CNB patients at 12 months compared with 43.7% with PER and 16.6% with BRV. Adverse events were less frequent with CNB (9.4% at 12 months) than in controls (35.3%) and were generally non-treatment-limiting. GLMMs confirmed a significant time × treatment interaction for seizure frequency, indicating a steeper reduction in CNB patients, while no significant interaction emerged for adverse events.
conclusionsIn this real-world study, early third-line CNB exhibits potentially favorable effectiveness compared with other commonly used third-line ASMs, and tolerability remained acceptable. These findings support the need for larger prospective studies to better define optimal treatment sequencing in focal-onset DRE.
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