Effectiveness, safety and tolerability of perampanel by age group when used to treat people with focal and generalized epilepsy in clinical practice: The PERMIT Extension study.

OBJECTIVE: To assess the effectiveness and safety/tolerability of perampanel (PER) in people with epilepsy (PWE) treated in everyday clinical practice for focal and generalized seizures, both in the total cohort and by age group. METHODS: The PERMIT Extension study was a pooled analysis of data from PWE included in two large previous clinical practice studies (PERMIT and PROVE). Retention was assessed over 12 months. Effectiveness was assessed based on total seizures and by seizure type (focal and generalized) after 3, 6, and 12 months of PER treatment and at final follow-up (last observation carried forward; "last visit"); assessments included responder rate (≥50% seizure frequency reduction from baseline) and seizure freedom rate (no seizures since at least the previous visit). Safety/tolerability was assessed throughout PER treatment by evaluating adverse events (AEs). All assessments were conducted for the total population and by age category (<12, ≥12 to <18, ≥18 to <65, and ≥65 years at baseline). RESULTS: Full Analysis Set included 6,822 PWE (51.1% female; mean age, 36.9 years; mean duration of epilepsy 21.4 years) with 6,433, 4,648, and 6,233 PWE assessed for retention, effectiveness, and safety/tolerability, respectively. The majority of PWE (81.1%) were aged 18-64 at baseline, with 4.5% aged <12 years, 8.4% aged 12-17 years, and 5.9% aged ≥65 years. In the overall population, retention rates at 3, 6, and 12 months were 88.0%, 77.6%, and 61.4%, respectively; responder rates at 12 months were 58.5% for total seizures, 54.6% for focal seizures, and 77.7% for generalized seizures, and corresponding seizure freedom rates were 23.6%, 19.0%, and 51.3%, respectively. PER was effective regardless of age category, although effectiveness was greatest in PWE aged ≥65 years, for both focal and generalized seizures. In the overall population, the incidence of AEs was 49.2% and the most frequent AEs (≥5% of PWE) were dizziness/vertigo (13.4%), somnolence (8.8%), irritability (7.3%), and behavioral disorders (5.3%); AEs led to treatment discontinuation in 18.3% of PWE over 12 months. The incidence of AEs and the discontinuation rate due to AEs increased with increasing age (55.0% and 23.9%, respectively, in PWE aged ≥65 years). CONCLUSION: In this study, the largest pooled analysis of PER clinical practice data conducted to date, PER was shown to be effective and generally well tolerated when used to treat people with focal or generalized epilepsy in everyday clinical practice, regardless of age category. No new or unexpected side effects emerged following long-term use in the real-world setting.

Perampanel for the treatment of epilepsy with genetic aetiology: Real-world evidence from the PERMIT Extension study.

Genetic factors contribute to the aetiology of epilepsy in >50% of cases, and information on the use of antiseizure medications in people with specific aetiologies will help guide treatment decisions. The PERMIT Extension study pooled data from two real-world studies (PERMIT and PROVE) to investigate the effectiveness and safety/tolerability of perampanel (PER) when used to treat people with focal and generalised epilepsy in everyday clinical practice. This post-hoc analysis of PERMIT Extension explored the use of PER when used to treat individuals presumed to have epilepsy with a genetic aetiology. Assessments included retention rate (evaluated at 3, 6 and 12 months), effectiveness (responder and seizure freedom rates; evaluated at 3, 6, 12 months and the last visit [last observation carried forward) and tolerability (adverse events [AEs]). Of the 6822 people with epilepsy included in PERMIT Extension, 1012 were presumed to have a genetic aetiology. The most common genetic aetiologies were idiopathic generalised epilepsy (IGE; 58.2%), tuberous sclerosis (1.1%), Dravet syndrome (0.8%) and genetic epilepsy with febrile seizures plus (GEFS+; 0.5%). Retention rates at 3, 6 and 12 months in the total genetic aetiology population were 89.3%, 79.7% and 65.9%, respectively. In the total genetic aetiology population, responder rates at 12 months and the last visit were 74.8% and 68.3%, respectively, and corresponding seizure freedom rates were 48.9% and 46.5%, respectively. For the specific aetiology subgroups, responder rates at 12 months and the last visit were, respectively: 90.4% and 84.4% (IGE), 100% and 57.1% (tuberous sclerosis), 100% and 71.4% (Dravet syndrome), and 33.3% and 20.0% (GEFS+). Corresponding seizure freedom rates were, respectively: 73.1% and 64.6% (IGE), 33.3% and 22.2% (tuberous sclerosis), 20.0% and 28.6% (Dravet syndrome), and 0% and 0% (GEFS+). The incidence of AEs was 46.5% for the total genetic aetiology population, 48.8% for IGE, 27.3% for tuberous sclerosis, 62.5% for Dravet syndrome, and 20% for GEFS+. Tolerability findings were consistent with PER's known safety profile. PER was effective and generally well tolerated when used in individuals with a presumed genetic epilepsy aetiology in clinical practice. PER was effective across a wide range of genetic aetiologies.

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

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.