Efficacy and Tolerability of Cenobamate in Treating Refractory Focal Epilepsy: Results From the 6-month Open-label Cenobamate in Focal Epilepsy Study (CIFES).

OBJECTIVES: Refractory epilepsy remains a major therapeutic challenge, affecting approximately one third of patients with persistent seizures despite treatment with multiple antiseizure medications (ASMs). Cenobamate (CNB), a novel ASM, has shown promising efficacy in both clinical trials and real-world settings. This observational study aimed to evaluate the efficacy, tolerability, and retention of CNB in adults with drug-resistant focal-onset seizures in routine clinical practice.

METHODS: A cross-sectional analysis was conducted on 40 patients treated with CNB at Santa Lucía University Hospital between 2022 and 2024. Seizure frequency, CNB discontinuation, adverse effects, and concomitant ASMs were assessed at 1, 3, and 6 months.

RESULTS: We found a significant reduction in mean monthly seizures, from 48.4 at baseline to 12.1 at 6 months ( P =0.0001). At 6 months, 48% of patients had a ≥50% seizure reduction, and 27% were seizure-free. In addition, CNB treatment was associated with a significant reduction in Defined Daily Doses and the number of concomitant ASMs. A 95% retention rate was observed among patients after 6 months on CNB treatment. Only 2 patients discontinued CNB, neither due to adverse effects. Reported adverse effects were mild to moderate, with somnolence (13%) and dizziness (10%) being the most common.

CONCLUSIONS: These findings reinforce CNB as a valuable treatment option for patients with focal-onset drug-resistant epilepsy, supporting its integration into clinical practice. Further research is needed to evaluate long-term outcomes and its potential role as a first-line therapy.