Abstracts

Rationale: Cenobamate has been approved by the FDA for treating adults with focal onset epilepsy and is considered an option for refractory patients. Data on its potential effectiveness and safety in subjects with developmental epileptic encephalopathies (DEE) is limited and based on case series.

Methods: Retrospective medical record review at a tertiary epilepsy center included patients with DEE who initiated treatment with cenobamate (CNB) between December 2019 - February 2022 and had at least one follow-up visit. Seizure etiology, associated syndromes, adverse effects and number of concomitant antiseizure medications (ASM) were recorded. The three and six-month retention and seizure freedom rates were evaluated. Patients were classified into three groups according to the clinical impression of the prescribing physician regarding seizure frequency and severity at the last follow-up visit: (i) improved, (ii) no change or (iii) worse. A one-way ANOVA was conducted to evaluate mean differences in age, body mass index, number of concomitant ASM, CNB dose and age of seizure onset between the groups. A logistic regression analysis was performed to ascertain potential predictors of three and six-month seizure freedom. Data are presented as mean ± standard deviation (min – max) or number (%). 

Results: Of the 192 patients who were prescribed CNB, 29 were diagnosed with a DEE and fulfilled the inclusion criteria. The clinical and demographic characteristics of the sample are displayed in Table 1. The duration of treatment was 9 ± 5 months (0 – 20 months). Improvement in seizure frequency and severity was observed in 22 (76%) participants, worsening in 2 (7%) and no change in 5 (17%). Of the two participants with worse seizures, one had a SCNA8-related epilepsy and the other had Tuberous Sclerosis. The CNB dose was higher in the group with improved seizures 211 ± 91 mg/day (50 – 400 mg/day) compared to that with no changes 80 ± 89 (12.5 – 200 mg/day), and worse seizures 87 ± 88 (25 – 150 mg/day) groups; p = .01.  The retention rate at 3 months was 25/29 (86%); 14 of these 25 patients (48%) achieved a three-month seizure freedom.  The six-months retention was reached by 19 of 24 patients (79%), six of whom (32%) were seizure-free for six months. Two participants discontinued treatment due to adverse effects and three due to ineffectiveness. Adverse effects were reported by 24/29 (83%). Sedation, the most common side effect, was reported by 15/29 (52%) subjects. The logistic regression analysis did not identify any statistically significant predictor of three or six-month seizure freedom.

Conclusions: These data suggest that CNB could be an effective and safe therapeutic option for patients with developmental epileptic encephalopathy, but this needs to be established in double-blind-placebo controlled trials. Despite the high rate of adverse effects, only a few led to the discontinuation of treatment, possibly due to improvement or resolution after reduction of concomitant ASM.

Funding: Not applicable