Experience of perampanel monotherapy beyond initial titration to achieve seizure freedom in patients with focal‐onset seizures with newly diagnosed or currently untreated recurrent epilepsy: A post hoc analysis of the open‐label Study 342 (FREEDOM)

Abstract

Objective: This post hoc analysis evaluated whether continued treatment with perampanel monotherapy beyond initial titration may be appropriate for patients with focal-onset seizures (FOS) with currently untreated epilepsy to achieve seizure freedom with an effective dose. Methods: Study 342 (NCT03201900; FREEDOM) is a single-arm, open-label, Phase III study of perampanel monotherapy. Patients aged ≥12 years with untreated FOS received perampanel 4 mg/d in a 32-week Treatment Phase (6-week Titration and 26-week Maintenance Periods); in case of seizure(s) during Maintenance Period, patients could enter a 30-week Treatment Phase (4-week Titration and 26week Maintenance Periods) to be up-titrated to perampanel 8 mg/d. The primary endpoint was seizure-freedom rate during Maintenance Period in the modified Intent-to-Treat (mITT) Analysis Set (patients who had ≥1 post-dose efficacy measurement during Maintenance Period); safety was monitored. This analysis of 4mg/d efficacy data assessed the proportion of patients achieving seizure freedom during the Maintenance Period (responders) relative to patients with an early/ later response (depending on seizure status during the Titration Period).

Perampanel Monotherapy for Focal and Generalized Epilepsy in Clinical Practice

“…Notably, in this trial, PWE who experienced a seizure when treated with PER 4 mg/ day during a 26-week maintenance period could be uptitrated to 8 mg/day and reassessed in an additional 26-week maintenance period [8]. A post hoc analysis of the trial demonstrated that a third of PWE who experienced seizures during the titration period of the 4 mg phase of the study went on to achieve seizure freedom during the maintenance period at 4 mg/day [27]. This led the authors to conclude that, in clinical practice, it may be inappropriate to discontinue or switch from PER monotherapy based solely on seizure response before an effective dose has been reached, since the half-life of PER is approximately 105 hours and it may take 2-3 weeks before steadystate plasma PER concentrations are attained [27].…”

“…A post hoc analysis of the trial demonstrated that a third of PWE who experienced seizures during the titration period of the 4 mg phase of the study went on to achieve seizure freedom during the maintenance period at 4 mg/day [27]. This led the authors to conclude that, in clinical practice, it may be inappropriate to discontinue or switch from PER monotherapy based solely on seizure response before an effective dose has been reached, since the half-life of PER is approximately 105 hours and it may take 2-3 weeks before steadystate plasma PER concentrations are attained [27]. In the current study, PER monotherapy was initiated using slow titration (<2 mg/week) in less than a quarter of PWE (22.3%).…”

GBAPerampanel Monotherapy- A Novel Treatment for Seizures: A Systematic Review

“…Husni et al [13] performed a post hoc analysis study of 342 PER monotherapy patients with focal onset seizures along with untreated recurrent epilepsy with an effective dose beyond initial titration to achieve seizure freedom. It is a single-arm, open-label, Phase-III study in patients with focal-onset seizures aged over 12 years, 4 mg/day with 30-week treatment phase of 4-week titration period and 26-weeks maintenance period.…”

Efficacy and tolerability of perampanel in patients with seizures in real-world clinical practice: A systematic review and meta-analysis

“…Ikemoto et al, 2019;Kanemura et al, 2019;Lin et al, 2019;Maschio et al, 2019;Stavropoulos et al, 2019;Takahashi et al, 2019;Abril Jaramillo et al, 2020;Coppola et al, 2020;Kim et al, 2020;Liguori et al, 2020;Maschio et al, 2020;Moraes et al, 2020;Pascarella et al, 2020;Santamarina et al, 2020;Toledano Delgado et al, 2020;Yamamoto et al, 2020;Basheikh and Sadler, 2021;Canas et al, 2021;Davis Jones et al, 2021;Im et al, 2021;Inoue et al, 2021;Labate et al, 2021;Lattanzi et al, 2021;Limotai and Jirasakuldej, 2021; Lossius et al, 2021;Nilo et al, 2021;Rodríguez- Osorio et al, 2021;Sagar et al, 2021;Zhang et al, 2021;Chinvarun, 2022;Husni et al, 2022). A diagram summarizing the process of study selection is shown in Figure1.…”