Cenobamate as an Early Adjunctive Treatment in Drug-Resistant Focal-Onset Seizures: An Observational Cohort Study

Abstract

Background and objectives: Cenobamate (CNB) is a new antiseizure medication (ASM) to treat drug-resistant, focal-onset seizures. Data on its use in early therapy lines are not yet available, and clinicians frequently consider CNB to be a later ASM drug choice. We investigated the efficacy and safety of CNB as an early adjunctive treatment in drug-resistant, focal-onset seizures.

Methods: The study population were patients with drug-resistant, focal-onset seizures who were initiated with CNB after they did not respond to two or three lifetime ASMs, including all prior and concomitant ASMs. These patients were matched (1:2) by sex, age, and seizure frequency to controls who were initiated with any ASM other than CNB. All participants participated in the Mainz Epilepsy Registry. We evaluated the retention rate after 12 months of CNB and after each new adjunctive ASM in the control group. In addition, seizure freedom and the response rate (reduction of seizure frequency by ≥ 50% from baseline) after 12 months were estimated.

Results: We included 231 patients aged 44.4 ± 15.8 years. Of these, 33.3% (n = 77) were on CNB, 19.0% (n = 44) on valproate (VPA), 17.3% (n = 40) on lacosamide (LCS), 16.4% (n = 38) on levetiracetam (LEV), and 13.9% (n = 32) on topiramate (TPM). The highest retention rate after 12 months since the beginning of the early adjunctive therapy was observed on CNB (92.0%), compared with LCS (80.0%), LEV (73.3%), VPA (68.2%), or TPM (62.5%) (p < 0.05). Seizure freedom and response rate were also the best on CNB (19.5% and 71.4%, respectively) compared with other ASMs (8.3% and 52.5%, respectively; p < 0.05). No significant differences in adverse events between CNB and other ASMs were observed.

Conclusions: Our study provides evidence that CNB is an effective ASM with a good safety profile in the early therapy lines of drug-resistant, focal-onset seizures. This data should support medical decision making in the management of patients with refractory epilepsy.

Clinical trial id: NCT05267405.

Fig. 1

12-month retention rates (%) across treatment groups. A *12-month retention rate of CNB was at p < 0.05 higher compared with LCS, LEV, TPM, or VPA. ^†12-month retention rate of LCS was at p < 0.05 higher compared with TPM, or VPA. ^‡12-month retention rate of LEV was at p < 0.05 higher compared with TPM. B *12-month retention rate of dual mechanism of action (SCB and GABAergic) was at p < 0.05 higher compared with other mechanisms of action. ^‡12-month retention rate of slow inactivators of sodium channels and SV2A modulators was at p < 0.05 higher compared with carbonic anhydrase inhibition. Abbreviations: CNB, cenobamate, LCS, lacosamide; LEV, levetiracetam; SCB, sodium channel blocker; TPM, topiramate; VPA, valproate

Fig. 2

Responder rates (%) after 12 months for all subtypes of seizures. Responder rates related to the percentage of patients reaching 50% or more, 75% or more, and 100% reduction in seizure frequency after 12 months in comparison with baseline. *Statistically significantly higher at p < 0.05 for the comparison of CNB with LCS, LEV, VPA, or TPM. ^†Statistically significantly higher at p < 0.05 for the comparison of CNB with LCS, LEV, or TPM. Abbreviations: CNB, cenobamate; LCS, lacosamide; LEV, levetiracetam; TPM, topiramate; VPA, valproate

Fig. 3

Responder rates (%) after 12 months among different seizure subtypes. Responder rates related to the percentage of patients reaching 50% or more, 75% or more, and 100% reduction in seizure frequency after 12 months in comparison with baseline. *Significantly higher at p < 0.05 in comparison with LCS, LEV, VPA, and TPM. ^†Significantly higher at p < 0.05 in comparison with LCS, LEV, and TPM. ^⍺Significantly higher at p < 0.05 in comparison with LCS. Abbreviations: CNB, cenobamate; LCS, lacosamide; LEV, levetiracetam; TPM, topiramate; VPA, valproate