Evaluation of real‐world effectiveness of perampanel in Japanese adults and older adults with epilepsy

Abstract

Objective. While previous studies have demonstrated the safety and effectiveness of perampanel (PER) in combination with other anti-seizure medications in adult patients, data for older patients are limited. This study aimed to confirm real-world safety and effectiveness of combination treatment with PER in Japanese patients with focal seizures with or without focal to bilateral tonic-clonic seizures (FBTCS) or generalised tonic-clonic seizures (GTCS) according to age subgroups (<65 and !65 years of age). Methods. This large-sample prospective post-marketing observational study included a 24-52-week observation period after the first PER treatment. Safety was assessed according to adverse drug reactions (ADRs) and efficacy was evaluated based on the 50% responder rate and rates of overall symptom improvement. Results. Among the 3,808 patients who were enrolled, 3,716 (3,026 patients aged <65 years and 690 patients aged !65 years) and 3,272 were included in the safety and efficacy analysis datasets, respectively. ADRs were reported for 1,247 patients (33.6%) in the safety analysis dataset. Of these, 36.2% and 22.2% were aged <65 years and !65 years, respectively, and the most common ADRs were somnolence (11.6%, 5.5%) and dizziness (9.7%, 5.4%). The 50% responder rates in patients aged <65 years and those !65 years were 60.1% and 89.0% for those with focal aware seizures (FAS) with motor signs; 48.0% and 60.0% for FAS without motor signs; 47.4% and 80.2% for focal impaired awareness seizures; 70.8% and 93.4% for FBTCS; and 63.6% and 88.9% for GTCS, respectively. The improvement rates of symptoms/conditions were also higher in patients aged !65 years than those <65 years. Significance. PER was effective in reducing seizure frequency and was safe, especially in older patients. PER may be a clinical treatment option for older patients with seizure disorders.

Optimal Use of Perampanel in Elderly Asian Patients with Epilepsy: Expert Opinion

“…The largest observational study to date investigated the efficacy and safety of long-term adjunctive perampanel treatment in Japanese patients who have epilepsy with focal seizures, with or without focal to bilateral tonic-clonic seizures or generalized tonic-clonic seizures (N=3716). 24 In a subgroup analysis of patients aged ≥65 years (n=690), the mean dose of perampanel used was 3.0 mg/day and the mean maximum dose was 3.5 mg/day – both of which were lower than those used in patients <65 years old. The 50% responder rates were higher in the elderly patient group, regardless of seizure type.…”

“…While falls have been reported to occur more frequently in elderly than adult patients on perampanel in clinical trials, 17 real-world analyses have not found this to be the case. 20 , 24 Such discrepancies could be explained by the high dosing (8–12 mg/day) and fast titration (daily dose uptitrated at 2 mg each week) 17 that are characteristic of the clinical trials. 20 This underpins the importance of the “start low and go slow” strategy for elderly patients.…”

“…Based on clinical trial data and real-world experience, perampanel is observed to have broad-spectrum efficacy in different seizure types, and good safety and tolerability profiles among elderly patients. [17][18][19][20][21][22][23][24] Clinical trial and real-world data focusing on this patient population are summarized below.…”

“…In this population, perampanel at doses lower than the indicated starting and maintenance doses for the general population offers effective seizure reduction while minimizing AEs. [22][23][24]…”

“…The expert group recommends that the optimal maintenance dose is 4 mg/day. As perampanel has demonstrated low-dose efficacy in elderly patients with minimal AEs, [22][23][24] the maintenance dose for this patient group can be lower than the recommended 8 mg/day for the general adult population.…”