Real-World Experience Treating Pediatric Epilepsy Patients With Cenobamate

Abstract

IntroductionIn one third of all patients with epilepsy, seizure freedom is not achieved through anti-seizure medication (ASM). These patients have an increased risk of earlier death, poorer cognitive development, and reduced quality of life. Cenobamate (CNB) has recently been approved as a promising novel ASM drug for the treatment of adults with focal-onset epilepsy. However, there is little experience for its application in pediatric patients.MethodsIn a multicenter study we evaluated retrospectively the outcome of 16 pediatric patients treated “off label” with CNB.ResultsIn 16 patients with a mean age of 15.38 years, CNB was started at an age of 15.05 years due to DRE. Prior to initiation of therapy, an average of 10.56 (range 3–20) ASM were prescribed. At initiation, patients were taking 2.63 (range 1–4) ASM. CNB was increased by 0.47 ± 0.27mg/kg/d every 2 weeks with a mean maximum dosage of 3.1 mg/kg/d (range 0.89–7) and total daily dose of 182.81 mg (range 50–400 mg). Seizure freedom was achieved in 31.3% and a significant seizure reduction of >50% in 37.5%. Adverse events occurred in 10 patients with fatigue/somnolence as the most common. CNB is taken with high adherence in all but three patients with a median follow-up of 168.5 daysConclusionCenobamate is an effective ASM for pediatric patients suffering from drug-resistant epilepsy. In addition to excellent seizure reduction or freedom, it is well-tolerated. Cenobamate should be considered as a novel treatment for DRE in pediatric patients.

Real‐world safety and effectiveness of cenobamate in patients with focal onset seizures: Outcomes from an Expanded Access Program

“…14 Regarding clinical practice, somnolence was the most frequently reported AE in one series, 23 and ataxia, sedation, somnolence, and vertigo were the most common AEs in pediatric series. 21,22 Although CNSrelated AEs were the most frequently reported AEs in all series, their severity does not appear to reduce cognitive outcomes over time. Indeed, a series of 50 patients treated with CNB who were evaluated prospectively using EpiTrack© remained stable or showed improved cognitive performance.…”

“…23 Similarly, a clinical practice study including 16 pediatric patients with a mean of 10.6 prior ASMs found a seizure freedom rate of 31% and a >50% response rate of 37.5%. 21 Finally, in a pediatric real-world study, 19% of patients achieved seizure freedom, 52% had a ≥75% response rate, and 63% had a ≥50% response rate. 22 Our favorable outcomes were also consistent with recent data from an EAP in Ireland, which included 57 patients with ultraresistant epilepsy and showed 75%-99% seizure reduction in 42.1% of the cohort.…”

“…[16][17][18] However, the number of publications with CNB in this setting are limited and include low numbers of patients. [19][20][21][22][23][24] Expanded Access Programs (EAPs) provide an opportunity to expand the real-world dataset for CNB in a larger series of patients in order to gain knowledge on its clinical use. 25 The aims of this study were to describe the demographics of patients participating in a Spanish EAP, to report the effectiveness and tolerability of CNB in a large population, and to collate information on the use of CNB in clinical practice.…”

Successful treatment of adult Dravet syndrome patients with cenobamate

“…11 In addition, we and others recently reported the effectiveness of CNB in pediatric cohorts with DRE. 12,13 The exact mode of action is unknown. CNB has been proposed to act on GABA A receptors as a positive allosteric modulator.…”

“…Cenobamate (CNB) is a new ASM that is approved to treat focal‐onset seizures in adults, with a promising seizure freedom rate of about 20% in patients with drug‐resistant focal epilepsy (DRE) 11 . In addition, we and others recently reported the effectiveness of CNB in pediatric cohorts with DRE 12,13 . The exact mode of action is unknown.…”