Abstracts

Rationale: Cenobamate (CNB), is an antiepileptic drug used to treat focal seizures in focal epilepsies. CNB positively modulates GABAA and inhibits voltage gated sodium channels. CNB was granted FDA approval in 2019, in Germany in 2021 and is applied to the adjunctive treatment of focal seizures in adult patients (pts) after a previous ineffective treatment with at least 2 antiseizure medications (ASM).

Methods: We sampled all data of therapy refractory epilepsy pts who got CNB between October 2020 and January 2022 in our tertiary epilepsy center and analyzed effect, side effects and retention. Median duration of CNB exposure was 7 months. Retention and effectiveness were based on data of the last visit carried out. Effectiveness assessments included 50% responder rate and seizure freedom rate (no seizures since at least the prior visit).

Results: We investigated 120 pts (52 women, 68 men) with a mean age of 40.4 years (17 to 77). We found pts with multifocal epilepsies (11), generalized epilepsies (12, Lennox-Gastaut syndromes), and focal epilepsies (97) with different etiologies: genetic causes (11), structural (52) autoimmune induced (12), or unclear (24). The comedication was lamotrigine (49), valproate (41), clobazam (35), brivaracetam/levetiracetam (37), lacosamide (15), oxcarbazepine (15), perampanel (7), zonisamide (5), stiripentol (5), topiramate (4), phenobarbital (2), rufinamide (1), felbamate (1), carbamazepine (1). Most of the pts had 2 or 3 ASM in comedication. CNB was given add-on to monotherapy in 10 pts, to dual-therapy in 57 pts, and to triple-therapy in 39 pts. In 14 pts, CNB was given add-on to more than 3 ASM. 7 pts had VNS. The mean dosage of cenobamate was 220 mg/d with a range of 50 to 400 mg/d. The retention rate after 6 month was 91.4%. Side effects were seen in 55 patients (elevated GGT in 20 pts, DRESS syndrome in 2 pts and more than 10 times dysarthria, obstipation, irritability, aggression, and double vision. 5 pts became seizure free, 65 pts achieved substantial reduction in seizure frequency, in 21 pts CNB had no or only minor effects. The subgroup of 44 pts with mental handicap show 1/44 pts with seizure freedom, one with MECP2 duplication syndrome. The rate of side effects was nearly the same in this subgroup, but we saw in 3 cases alternative psychosis as a side effect in pts with initially good response to CNB.

Conclusions: Overall, adjunct CNB has been found to be generally safe and effective for treatment-resistant seizures in adult pts, a few therapy-resistant pts got seizure free and the retention rate, a mixture of effect and side effects was 91.4% after 6 months.

Funding: None