Cenobamate in adult patients with epilepsy and intellectual disability

In people with intellectual disability (ID), prevalence of epilepsy is up to 50-times higher than in the general population and often difficult to treat. Multiple randomized controlled, observational and retrospective studies have demonstrated favorable efficacy of adjunctive cenobamate (CNB). So far, people with epilepsy and ID (PWE+ID) have remained significantly underrepresented. This retrospective study evaluated efficacy and tolerability of CNB specifically in adult PWE+ID compared to those without ID (PWE-ID).

Between 2021 and 2024, PWE at a tertiary epilepsy center were surveyed by telephone on a quarterly basis as part of clinical quality control after starting CNB. Retention rate, seizure outcome (comparing the preceding 3 months to 3 months baseline), and adverse events were assessed. Chi-square and Mann-Whitney U tests were used to compare groups, and a Bayesian analysis evaluated non-inferiority.

A total of 108 PWE (51 PWE+ID) were monitored over 12 months after CNB initiation. Retention rates significantly differed between patients with and without ID after 3 months (100 % vs. 84 %, p = 0.04), but were not different after 6 (88 % vs. 77 %, p = 0.57) and 12 months (75 % vs. 70 %, p = 0.99). The 50 % responder rates were comparable at 6 months (46 % in PWE+ID vs. 47 % in PWE-ID, p = 0.99) and at 12 months (53 % vs. 53 %, p = 0.99). At 12 months, 21 % of PWE+ID (13 % of PWE-ID, p = 0.69) have remained free of disabling seizures. In Bayesian analysis, the probability of non-inferiority of 12-month outcomes in PWE+ID compared to PWE-ID was 97 % for retention and 94 % for 50 % responder rates. Adverse events (most frequently tiredness and dizziness) were reported by 59 % of PWE+ID (60 % of PWE-ID, p = 0.99) and resulted in CNB discontinuation within 12 months in 24 % of PWE+ID (28 % of PWE-ID, p = 0.70).

In adult PWE and intellectual disability, cenobamate is similarly efficacious and tolerated as in patients without ID.