Perampanel in Chinese patients with Dravet syndrome: Efficacy and tolerability assessed via a multicenter, prospective, real‐world observational study

Objective As a third‐generation antiseizure medication, the efficacy of perampanel in treating Dravet syndrome (DS) remains incompletely characterized. This multicenter, prospective, real‐world observational study aimed to evaluate the efficacy and long‐term tolerability of perampanel as adjunctive therapy in Chinese patients with DS. Methods Patients with unresolved DS were enrolled from four participating hospitals in China between January 2019 and December 2023. All patients received perampanel as add‐on therapy. Efficacy and retention rate were evaluated at 3, 6, and 12 months of perampanel treatment. Genetic screening for SCN1A mutations was performed in all enrolled patients. Results Fifty‐six patients were enrolled, of whom 48 (85.71%) harbored SCN1A mutations. The mean treatment duration of perampanel was 25.00 ± 7.65 months, with a mean maximum daily perampanel dose of 3.94 ± 1.19 mg. The retention rates at 6 and 12 months were 69.64% and 64.29%, respectively. After 6 and 12 months of treatment, the ≥50% responder rates were 66.07% and 60.71%, while seizure‐freedom rates were 21.43% and 12.50%, respectively. Seizure exacerbation occurred in three patients (5.36%). Adverse events occurred in six patients during treatment (three discontinued treatment), with no new safety concerns identified. Among 30 patients with ≥50% seizure frequency reduction throughout 12‐month treatment who carried SCN1A mutations, 33.33% had truncating mutations, 46.67% had missense mutations, 13.33% had splice site mutations, 3.33% had in‐frame mutations, and 3.33% had large chromosomal deletions encompassing SCN1A . No significant difference in the ≥50% seizure frequency reduction rate was observed between patients with SCN1A truncating mutations and those with missense mutations. Additionally, treatment response to perampanel did not differ significantly according to the specific mutation regions within the Nav1.1 sodium channel. Conclusions Perampanel demonstrated favorable efficacy and acceptable long‐term tolerability as adjunctive therapy in Chinese patients with DS. The efficacy of perampanel remained consistent regardless of the specific genotype or location of SCN1A mutations.