Rationale: Cenobamate (CNB) was approved by the FDA in adults in November 2019 for the treatment of focal seizures. We report our experience (typical level 4 epilepsy center) with CNB.
Methods:
We conducted a retrospective chart review of patients placed on CNB at our epilepsy center since its approval in November 2019. The primary outcome measure for efficacy was mean percent reduction in seizure frequency per month, Additional outcome measures for tolerability and safety included retention rate and adverse effects (AEs). Subgroup analysis was performed on patients on concurrent VNS use and patients on three classes of concomitant ASMs: 1) SV2A modulators (levetiracetam, brivaracetam), 2) AMPA antagonists (perampanel), or 3) sodium-channel blockers (carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin). Statistical analysis was performed with one-sample and two-sample t-tests at the alpha = 0.05 level of significance using the program XLSTAT.
Results:
N=72 patients were included (44% male, 56% female). The average age was 35.2 years (range 17-74 years). Epilepsy types included focal (90%, N=65) and generalized (10%, N=7). Focal epilepsy subtypes included temporal (56%), poorly localized (13%), frontal (12%), hemispheric (12%), multifocal (5%), and occipital (2%). Generalized epilepsy subtypes included Lennox-Gastaut syndrome or Developmental Epileptic Encephalopathies (71%) and idiopathic generalized epilepsy (29%). CNB was used as adjunctive treatment in all cases. The average number of concomitant ASMs was 2.71 (range 1-5). The average dose of CNB at endpoint was 218.1 mg (range 12.5-400 mg) and average treatment duration was 12.9 months (range 0.1-29 months).
Efficacy: For focal epilepsy, there was a significant reduction of 45.0% in mean seizure frequency (95% CI 35.4 to 54.7, p< 0.0001). For generalized epilepsy, there was a mean seizure frequency reduction of 31.4%, lower but still significant (95% CI 2.0 to 60.9, p = 0.041).
Tolerability: CNB was well-tolerated with retention rates at three months, six months, and 12 months of 86%, 80%, and 75%, respectively. AEs were common and occurred in 50% of patients. 23.6% of patients stopped CNB due to AEs. The most common AEs encountered were dizziness (15.3%), followed by somnolence (9.7%), gait ataxia (8.3%), fatigue (5.6%), diplopia (4.2%), rash (2.8%), and pruritis (1.4%). Compared to patients who continued CNB, patients who discontinued CNB had a significantly higher proportion of sodium-channel blocker use (83% vs 54%, p = 0.010).
Subgroup analysis showed no significant difference in mean seizure reduction with concurrent VNS use, SV2A modulator use, AMPA antagonist use, or sodium-channel blocker use (p-values of 0.466, 0.420, 0.443, and 0.117, respectively).
Conclusions:
CNB significantly reduced mean seizure frequency per month in both focal and generalized epilepsy types, with good overall safety and tolerability, although tolerability was significantly lower in patients with concomitant sodium-channel blocker use.
Funding: None