Abstracts

Rationale:
Nearly eighty percent of Tuberous Sclerosis Complex (TSC) patients have intractable epilepsy. This study aims to assess the efficacy of cenobamate (CBM) in controlling seizures in patients with TSC who have intractable epilepsy, where there is limited information on this population.

Methods:
We performed a retrospective review to identify TSC patients with epilepsy who received CBM at Cincinnati Children’s Hospital, USA, from January 2021 until May 2023. Seizure frequency (parental report) within the three months before CBM initiation was considered the baseline, and follow-up seizure frequency at 3, 6, 12, and 18 months post-CBM initiation data was collected. We excluded patients with insufficient information at baseline or at more than half of the follow-ups within the duration of CBM treatment. We defined responder rate and seizure-free rates as the proportion of patients with ≥ 50% and 100% reduction in seizure frequency compared to the baseline, respectively.

Results:
Seventy patients with TSC received CBM, and 16 were excluded due to insufficient data per exclusion criteria. Fifty-four patients aged 2 to 39 years (median 17.9, IQR 9.5) were included. The age of seizure onset ranged from one day to four months (mean 7.9 ± 14.6 months), and the epilepsy duration before CBM averaged 16.6 ± 9.2 months. The mean baseline seizure frequency was 66.1 (± 88.9) per month, including all seizure types. They took a median of three concurrent ASMs and used eight other ASMs in the past. Fifteen patients (27.8%) had a vagus never stimulator (VNS), and 23 (42.6%) had previous resective epilepsy surgery. CBM treatment duration ranged from 3 to 28 months (mean 14.9 ± SD 7.4 months). The mean dose was 4.5 mg/kg/day (± 2.3), and the mean daily dose was 246 mg (± 132). Treatment retention rates at 3, 6, 12, and 18 months were 94.4%, 79.6%, 66.7%, and 44.4%, respectively. Of all patients, regardless of their follow-up duration, the responder rates were 30% at three months, 28% at 6 months, 31% at 12 months, and 24% at 18 months. The seizure-free rates were 5.6%, 7.4%, 3.7%, and 3.7% at the respective follow-ups. Side effects were seen in 35 (64.8%) patients; most commonly sedation (23, 42.6%), behavioral disturbance (13, 24.1%), and gastrointestinal disturbance (12, 22.2%). Three patients (5.6%) had sleep disturbance, and three had dizziness. One patient (1.9%) stopped CBM due to intolerable behavioral side effects, and four (7.4%) stopped due to lack of efficacy. No patient developed drug rash with eosinophilia and systemic symptoms (DRESS).

Conclusions:
This study showed lower responder and seizure-free rates than the pivotal trials for CBM and most published real-world experiences, suggesting a highly intractable nature of seizures in the TSC population. Side effects were common, particularly sedation and behavioral disturbances. While CBM demonstrates a potential to reduce seizures in the TSC population, this study underscores the persistent demand for highly effective antiseizure treatments.

Funding: None