Perampanel for Treatment of People with a Range of Epilepsy Aetiologies in Clinical Practice: Evidence from the PERMIT Extension Study

Abstract

Introduction: It is important to assess the effectiveness of an antiseizure medication in treating different epilepsy aetiologies to optimise individualised therapeutic approaches. Data from the PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) Extension study were used to assess the effectiveness and safety/tolerability of perampanel (PER) when used to treat individuals with a range of epilepsy aetiologies in clinical practice.

Methods: A post hoc analysis was conducted of PERMIT Extension data from individuals with a known aetiology. Retention was assessed after 3, 6 and 12 months. Effectiveness was assessed after 3, 6 and 12 months and at the last visit (last observation carried forward). Effectiveness assessments included responder rate (≥ 50% seizure frequency reduction) and seizure freedom rate (no seizures since at least the prior visit). Safety/tolerability was assessed by evaluating adverse events (AEs) and AEs leading to discontinuation.

Results: PERMIT Extension included 1945 individuals with structural aetiology, 1012 with genetic aetiology, 93 with an infectious aetiology, and 26 with an immune aetiology. Retention rates at 12 months were 61.1% (structural), 65.9% (genetic), 56.8% (infectious) and 56.5% (immune). At the last visit, responder rates (total seizures) were 43.3% (structural), 68.3% (genetic), 37.0% (infectious) and 20.0% (immune), and corresponding seizure freedom rates were 15.8%, 46.5%, 11.1% and 5.0%, respectively. AE incidence rates were 58.0% (structural), 46.5% (genetic), 51.1% (infectious) and 65.0% (immune), and corresponding rates of discontinuation due to AEs over 12 months were 18.9%, 16.4%, 18.5% and 21.7%, respectively. The types of AEs reported were generally consistent across aetiology subgroups, with no idiosyncratic AEs emerging.

Conclusion: Although PER was effective and generally well tolerated when used to treat individuals with a range of epilepsy aetiologies in clinical practice, variability in its effectiveness and tolerability across the subgroups indicates that PER may be particularly useful for individuals with specific epilepsy aetiologies.

Keywords: Anticonvulsant; Antiepileptic drug; Antiseizure medication; Focal seizures; Generalized seizures; Real-world.

Fig. 1

Retention rates after 3, 6 and 12 months of PER treatment in the total aetiology population and by aetiology subgroup (retention population). PER perampanel

Fig. 2

Kaplan–Meier plot for retention on PER treatment over 12 months a in the total aetiology population and b by aetiology subgroup (structural, genetic, infectious and immune aetiologies; retention population). Statistically significant differences were observed between aetiologies (p = 0.002; log rank test). PER perampanel

Fig. 3

Responder rate, seizure freedom rate and the proportions of individuals with unchanged and worsening seizure frequency for total seizures at 3, 6 and 12 months and the last visit in a total aetiology population, b structural aetiology subgroup, c genetic aetiology subgroup, d infectious aetiology subgroup and e immune aetiology subgroup (effectiveness population)

Fig. 4

Responder rate, seizure freedom rate and the proportions of individuals with unchanged and worsening seizure frequency for focal seizures at 3, 6 and 12 months and the last visit in a total aetiology population, b structural aetiology subgroup, c genetic aetiology subgroup, d infectious aetiology subgroup and e immune aetiology subgroup (effectiveness population)

Fig. 5

Responder rate, seizure freedom rate and the proportions of individuals with unchanged and worsening seizure frequency for generalised seizures at 3, 6 and 12 months and the last visit in a total aetiology population, b structural aetiology subgroup, c genetic aetiology subgroup and d infectious aetiology subgroup (effectiveness population). Note: there were no individuals in the immune aetiology subgroup who had data available for generalised seizures

Fig. 6

Kaplan–Meier plot for retention on PER treatment over 12 months in the three structural aetiology subgroups (tumour, vascular and TBI aetiologies; retention population). No statistically significant differences were observed between aetiologies (p = 0.906; log rank test). PER perampanel, TBI traumatic brain injury

Fig. 7

Responder rate, seizure freedom rate and the proportions of individuals with unchanged and worsening seizure frequency for focal seizures at 3, 6 and 12 months and the last visit in a tumour aetiology subgroup, b vascular aetiology subgroup, c TBI aetiology subgroup (effectiveness population). TBI traumatic brain injury