Beyond seizure control: Non–seizure‐related outcomes in focal‐onset epilepsy treated with adjunctive cenobamate. Third interim results from the BLESS study

Abstract Objective Cenobamate is approved for treatment of focal seizures in adults, but evidence on non‐seizure outcomes remains limited. This interim statistical analysis of the cenoBamate in aduLts with focal‐onsEt SeizureS (BLESS) study evaluated patient‐ and clinician‐reported outcomes for up to 52 weeks of cenobamate treatment. Methods BLESS is an observational, retrospective and prospective cohort study designed to assess the real‐world effectiveness and safety of adjunctive cenobamate in adults with uncontrolled focal epilepsy. Outcomes included patient‐reported health‐related quality of life, sleepiness, anxiety, mood, and global functioning assessed by the 31‐item Quality of Life in Epilepsy Inventory (QOLIE‐31), the Epworth Sleepiness Scale (ESS), the Hospital Anxiety and Depression Scale (HADS), and the Clinical Global Impression (CGI) scales. Results A total of 377 participants were included. Among subjects with an available score at 12 ( n = 197), 24 ( n = 363), and 52 ( n = 197) weeks, the QOLIE‐31 overall score remained stable. Subjects with sustained seizure freedom at 24 weeks showed a significantly higher QOLIE‐31 overall score ( p = 0.041) and cognitive functioning scores ( p = 0.019) compared with those who did not reach sustained seizure freedom. More than 68% of participants had normal daytime sleepiness (total ESS score 0–10) and did not report anxiety or depression according to the HADS‐A and HADS‐D subscales at each assessment up to 52 weeks. Clinicians rated 91.3% ( n / N = 179/196), 85.7% ( n / N = 300/350), and 87.4% ( n / N = 167/191) of subjects as improved for their overall condition from the initiation of treatment according to the CGI—Improvement or change (CGI‐I) scale, at 12, 24, and 52 weeks. Significance This interim analysis provides preliminary descriptive evidence on non‐seizure outcomes in subjects treated with adjunctive cenobamate. Patient‐reported outcome scores remained stable from 12 weeks and up to 52 weeks, consistent with preserved overall well‐being. Better quality of life and cognitive functioning emerged in sustained vs non‐sustained seizure‐free participants. Based on clinicians' judgment, there was signal of improvement in overall condition compared to baseline in most treated subjects throughout the observation period. Study Registration NCT05859854.