Authors :
Presenting Author: Michal Tzadok, MD – Safra Children's Hospital, Sheba Medical Center
Rinat Komargodski, BSc – Shamir Medical Center
Eli Heyman, MD – Shamir medical center
Bruria Ben Zeev, MD – Safra Children's Hospital, Sheba Medical Center
Leo Arkush, MBBS BSc (Hons) – Safra Children's Hospital, Sheba Medical Center
Rationale:
Cenobamate is a new oral antiseizure medication (ASM) associated with other carbamate-containing ASMs which have been in longstanding use such as felbamate. It is thought to act by reducing repetitive neuronal firing by inhibiting voltage-gated sodium currents, and also modulates the GABA-A receptor. Cenobamate was approved by the US Food and Drug Administration for treatment of focal, drug resistant epilepsy in adults in November 2019 and is at present given off-label to children in some countries. Randomized controlled trials as well as open-label extension studies demonstrated significant reductions in seizure frequency and high responder rates, with good long-term treatment retention in adults. However, there is limited data in the pediatric population. We aimed to investigate the efficacy and tolerability of cenobamate in the pediatric population in a retrospective multicenter study.
Methods:
We performed a retrospective real-world study in two Israeli tertiary referral centers for epilepsy (Safra Children’s Hospital, Sheba Medical Center and Shamir Medical Center). Patients were included if they had focal, drug resistant epilepsy between the ages of 0-21 years and received cenobamate with at least 6 months follow-up. The primary outcome was treatment response at 3, 6 and 12 months. Secondary outcomes were adverse effects, retention rates and change in concomitant ASMs. We extensively characterized seizure and epilepsy types, epilepsy etiology, previous and concomitant ASMs, history of epilepsy surgery and neuromodulation and developmental/cognitive background of all patients.
Results:
48 patients were included in the analysis. Preliminary data shows that median age of epilepsy onset was 3 years with a background of development delay/intellectual disability in 53%. 35% had a genetic etiology and 38% had structural etiology. Cenobamate was initiated after a median of 8 previous ASMs at a median age of 12 years; of note 47% patients were under the age of 12 years. Overall 68% had seizure reduction at 3 months; further data will be presented of 6 and 12 month follow-up. 24% reported adverse effects at 3 months. 38% discontinued cenobamate treatment during follow-up. Dose reduction was performed in particular with lacosamide and clobazam due to suspected/reported interactions.
Conclusions:
Our study provides evidence that cenobamate is an effective and overall well-tolerated ASM in children and adolescents. Significantly, we demonstrate this in the younger pediatric population, which has not previously been reported in the literature. Our findings support the administration of cenobamate in children and adolescents with focal, drug resistant epilepsy as adjunctive therapy alongside the use of more established ASMs, although with caution required regarding drug interactions. Large prospective trials are required to confirm these findings in children.
Funding: Not applicable