Sustained seizure reduction, treatment simplification, and high retention with cenobamate: A 12‐month real‐world study in refractory and ultra‐refractory focal epilepsy
Francesca Cutropia, Maria Teresa Di Claudio, Marta Robustella, Umberto Costantino, Carmela Pia Ferro, Giuseppe Miscio, Elena Conte, Nicola Amoroso, Orazio Nicolotti, Cosimo Damiano Altomare, Massimo Carella, Antonella Liantonio, Paola Imbrici, Giuseppe d'OrsiAbstract
Objective
To assess the 12‐month clinical impact of cenobamate (CNB) in adults with drug‐resistant focal epilepsy in clinical practice, exploring whether outcomes differed according to prior antiseizure medication (ASM) exposure.
Methods
This single‐center, retrospective, observational, real‐world study included 91 adults stratified by the number of prior ASMs: ≤ 6 prior ASMs ( n = 44) and > 6 prior ASMs ( n = 47). Outcomes assessed at 3, 6, and 12 months included monthly seizure frequency, seizure freedom, retention rate, CNB dose, concomitant ASM burden, and adverse drug reactions (ADRs).
Results
In the overall cohort, mean monthly seizure frequency decreased from 28.77 at baseline to 22.73 (3 months), 19.37 (6 months), and 14.58 (12 months), representing mean reductions of 21%, 33%, and 49%, respectively. Seizure freedom was achieved by 12% (11/91) of patients at 3 months, 13% (11/87) at 6 months, and 19% (16/82) at 12 months. Treatment retention rate was 100% at 3 months, 95.6% at 6 months, and 90.1% at 12 months. Both subgroups showed clinical benefit, but outcomes were more favorable in patients with ≤ 6 prior ASMs, who had a lower baseline seizure burden and higher 12‐month seizure freedom than those with > 6 prior ASMs (29% vs. 10%). At 12 months, most patients were receiving CNB doses of 200 mg or higher, and 79% were maintained on ≤ 2 concomitant ASMs. Overall, 38.5% (35/91) of patients reported at least one ADR (most frequently somnolence, vertigo, and asthenia).
Significance
In this real‐world cohort of adults with drug‐resistant focal epilepsy, CNB was associated with sustained seizure reduction, high 12‐month retention rate, and acceptable tolerability, while most patients were maintained on a low concomitant ASM burden during follow‐up. Improvement was observed even in highly treatment‐experienced patients, although outcomes were more favorable in those with lower prior ASM burden, supporting the hypothesis that earlier CNB positioning may provide greater efficacy.