OBJECTIVE: To examine the efficacy and safety of perampanel (PER) in patients with post-stroke epilepsy (PSE), brain tumor-related epilepsy (BTRE), and post-traumatic epilepsy (PTE) using Japanese real-world data.
METHODS: The prospective post-marketing observational study included patients with focal seizures with or without focal to bilateral tonic-clonic seizures who received PER combination therapy. The observation period was 24 or 52 weeks after the initial PER administration. The safety and efficacy analysis included 3716 and 3272 patients, respectively. This post hoc analysis examined responder rate (50% reduction in seizure frequency), seizure-free rate (proportion of patients who achieved seizure-free), and safety in patients included in the post-marketing study who had PSE, BTRE, and PTE in the 4 weeks prior to the last observation.
RESULTS: Overall, 402, 272, and 186 patients were included in the PSE, BTRE, and PTE subpopulations, and 2867 controls in the \"Other\" population (etiologies other than PSE, BTRE, or PTE). Mean modal dose (the most frequently administered dose) values at 52 weeks were 3.38, 3.36, 3.64, and 4.04 mg/day for PSE, BTRE, PTE, and \"Other,\" respectively; PER retention rates were 56.2%, 54.0%, 52.6%, and 59.7%, respectively. Responder rates (% [95% confidence interval]) were 82% (76.3%-86.5%), 78% (70.8%-83.7%), 67% (56.8%-75.6%), and 50% (47.9%-52.7%) for PSE, BTRE, PTE, and \"Other,\" respectively, and seizure-free rates were 71% (64.5%-76.5%), 62% (54.1%-69.0%), 50% (40.6%-60.4%), and 28% (25.8%-30.1%), respectively. Adverse drug reactions tended to occur less frequently in the PSE (14.7%), BTRE (16.5%), and PTE (16.7%) subpopulations than in the \"Other\" population (26.3%).
CONCLUSIONS: In real-world clinical conditions, efficacy and tolerability for PER combination therapy were observed at low PER doses for the PSE, BTRE, and PTE subpopulations.
CONCLUSIONS: To find out how well the medication perampanel works and whether it is safe for people who have epilepsy after having had a stroke, brain tumor, or head injury, we used information from real-life medical situations in Japan. We looked at the data of about 3700 Japanese patients with epilepsy who were treated with perampanel. We found that perampanel was used at lower doses and better at controlling seizures, and had fewer side effects for patients with epilepsy caused by these etiologies than the control group.

BACKGROUND: Data on the efficacy of perampanel in refractory status epilepticus (RSE) and postanoxic encephalopathy (PAE) are limited; its use in such conditions is currently off-label.
METHODS: We conducted a retrospective cohort study of consecutive adult patients with RSE, including PAE, exhibiting electroencephalographic patterns indicative of status epilepticus who were treated at our center (January 2018 to December 2022) with assessment of clinical and electroencephalographic outcomes.
RESULTS: Thirty-six patients were included in the study, of whom 29 had nonanoxic RSE and 7 had PAE. Within the nonanoxic RSE subgroup, 45% (13 of 29; 95% confidence interval [CI] 27-63%) of study participants were responders, 34% (10 of 29; 95% CI 17-52%) were partial responders, and 21% (6 of 29; 95% CI 6-35%) were nonresponders. In the PAE subgroup (n = 7), no patients fully responded to perampanel; 43% (3 of 7; 95% CI 6-80%) were partial responders, and 57% (4 of 7; 95% CI 20-95%) were nonresponders. Responder and nonresponder study participants exhibited overlapping baseline characteristics. No significant differences in duration of hospitalization were observed between responders and nonresponders in both subgroups. Responders in the RSE subgroup had a median discharge modified Rankin Scale score of 3 (interquartile range 3-4), and nonresponders had a median discharge modified Rankin Scale score of 5 (interquartile range 5-6).
CONCLUSIONS: Despite limitations from the retrospective design and the small population size, this study suggests that perampanel use in nonanoxic RSE appears to yield promising results at moderate doses, including a tendency toward a better functional outcome at discharge, without significant adverse effects. However, in patients with PAE, the drug seems to show suboptimal performance. Perampanel appears to have promising efficacy as an add-on therapy in nonanoxic RSE. However, in patients with PAE, its efficacy seems to be lower. Further studies are warranted to confirm these observations.

OBJECTIVE: We aimed to identify factors that contribute to the discontinuation of perampanel.
METHODS: We retrospectively analyzed patients with epilepsy at the Department of Psychiatry, Hokkaido University Hospital. We evaluated the factors contributing to perampanel discontinuation as primary outcomes using Cox proportional hazards regression. Then, we explored the components contributing to the primary outcomes using logistic regression analysis.
RESULTS: A total of 118 patients were included, 44.9% of whom discontinued participation, 22.0% had intellectual disability, and 23.7% had a psychiatric disorder other than intellectual disability. Adverse effects occurred in 65% of the patients, 23.7% had psychiatric adverse effects (PAE), and 49.2% had common adverse effects (CAE). The effect of PER to suppress seizures was confirmed in 65.3% of them. Discontinuation was influenced by non-response (Hazard Ratio (HR) 6.70, 95% Confidence Interval (CI) 3.42-13.1), the occurrence of PAE (HR 3.68, 95% CI 1.89-7.16), CAE (HR 1.90, 95% CI 1.06-3.41), and comorbid psychiatric disorders (HR 2.35, 95% CI 1.21-4.59). Moreover, comorbid intellectual disability correlated with a low risk of PAE (OR 0.19, 95% CI 0.04-0.89).
CONCLUSIONS: The discontinuation of perampanel is influenced by poor efficacy and the occurrence of common/psychiatric adverse effects. The discontinuation of perampanel is influenced by poor efficacy and the occurrence of common/psychiatric adverse effects. Consideration of factors contributing to perampanel discontinuation may assist in determining the indication for perampanel treatment.

ELEVATE (Study 410; NCT03288129) is the first prospective, multicenter, open-label, Phase IV study of perampanel as monotherapy or first adjunctive therapy in patients aged ≥ 4 years with focal-onset seizures or generalized tonic-clonic seizures in the United States. The study included Screening, Titration (≤ 13 weeks), Maintenance (39 weeks), and Follow-up (4 weeks) Periods. During Titration, perampanel was initiated at 2 mg/day and up-titrated to 4 mg/day at Week 3. Depending on response and tolerability, optional up-titrations to a maximum of 12 mg/day occurred. The primary endpoint was retention rate; additional endpoints included seizure-freedom rate, 50% responder rate, and incidence of treatment-emergent adverse events (TEAEs). At baseline, 10 (18.5%) patients were assigned to the monotherapy group and 44 (81.5%) patients to the first adjunctive therapy group. However, due to the addition of an anti-seizure medication along with perampanel on the first day of treatment, one patient was excluded from the monotherapy subgroup analyses. The mean perampanel exposure duration was 39.8 weeks and 32 (59.3%) patients completed the study. Retention rate at 12 months (or study completion) was 63.0% (monotherapy, 77.8%; first adjunctive therapy, 59.1%). Seizure-freedom rate during the Maintenance Period was 32.7% (monotherapy, 44.4%; first adjunctive therapy, 29.5%) and the 50% responder rate was 78.7% (monotherapy, 85.7%; first adjunctive therapy, 76.9%). TEAEs and serious TEAEs were reported by 88.9% (n = 48/54) and 7.4% (n = 4/54) of patients, respectively. Overall, the efficacy and safety of perampanel as monotherapy or first adjunctive therapy support the use of perampanel as early-line treatment for epilepsy.

OBJECTIVE: To determine the efficacy and safety of perampanel (PER) as an adjunctive therapy in children aged 4-12 years with epilepsy.
METHODS: We performed a non-randomized, open-label, placebo-uncontrolled, real-world self-controlled study that included 216 young children (aged 4-12 years) with epilepsy who received PER as adjunctive therapy at the children\'s hospital affiliated with Chongqing Medical University from July 4, 2020, to September 20, 2023.
RESULTS: (1) The efficacy rates of adjunctive PER therapy at 3, 6, 9, and 12 months were 62.8%, 67.8%, 65.3%, and 61.2%, respectively. PER showed efficacy in alleviating focal seizures, generalized tonic-clonic seizures, myoclonic seizures, and absence seizures. The efficacy rates for variants of self-limited epilepsy with centrotemporal spikes (SeLECTS) and Lennox-Gastaut syndrome (LGS) were 89.5% and 66.7%, respectively. (2) Focal non-motor onset seizures with or without impaired awareness, focal to bilateral tonic-clonic seizures (FBTCS), LGS, variants of SeLECTS, the number of concomitant antiseizure medications (ASMs), a family history of epilepsy, and focal lesions on cranial magnetic resonance imaging were independent factors affecting efficacy. The order of PER addition did not affect efficacy. The retention rates at 3, 6, 9, and 12 months were 90.7%, 84.7%, 74.7%, 64.9%, respectively. (3) Adverse reactions occurred in 45 patients (45/216, 20.8%), with irritability/aggressive behavior (18/216, 8.3%) and somnolence (14/216, 6.5%) being the most common. Twelve patients (12/216, 5.6%) withdrew from the study because of adverse reactions.
CONCLUSIONS: In young Chinese children with epilepsy, PER is effective, safe, and well-tolerated as an adjunctive therapy, making it a viable option for use with broad-spectrum ASMs.

OBJECTIVE: The purposes of this study were to explore the pharmacokinetics of perampanel (PER) in children with epilepsy, identify factors that contribute to pharmacokinetic variations among subjects, evaluate the connection between PER exposure and clinical outcome, and establish an evidence-based approach for tailoring individualized antiepileptic treatment in this specific population.
METHODS: In this prospective study, PER plasma concentrations and genetic information on metabolic enzymes were obtained from 194 patients younger than 18 years. The disposition kinetics of PER in pediatric patients following oral dosing were characterized using nonlinear mixed effect models. The effective range for the plasma concentration of PER was determined by assessing the efficacy and safety of PER treatment and analyzing the relationship between drug exposure and clinical response. Monte Carlo simulations were then performed to evaluate and optimize the current dosing regimens.
RESULTS: The pharmacokinetic profile of PER was adequately described by a one-compartment model with first-order absorption and elimination. Body weight, total bilirubin level, and concomitant oxcarbazepine were found to have significant influences on PER pharmacokinetics. Model estimates of apparent clearance and volume of distribution were .016 ± .009 L/h/kg and 1.47 ± .78 L/kg, respectively. The effective range predicted from plasma concentration data in responders was 215-862 μg/L. Dosing scenarios stratified according to essential covariates were proposed through simulation analysis.
CONCLUSIONS: In this study, we captured the pharmacokinetic/pharmacodynamic characteristics of PER in pediatric epilepsy patients through analysis of real-world data and adopted a pharmacometric approach to support an individualized dosing strategy for PER in this specific population.

BACKGROUND: The non-interventional Phase IV PROVE study (NCT03208660) assessed retention, efficacy, safety and tolerability, and perampanel dosing in patients with epilepsy during routine clinical care. This analysis evaluated final data from patients aged <4 years and 4-<12 years.
METHODS: Data were obtained retrospectively from medical/pharmacy records of patients in the United States initiating perampanel after January 1, 2014, according to treating clinician recommendations. Retention rate was the primary endpoint. Secondary assessments included median percent changes in seizure frequency, seizure-freedom rates, investigator impression of seizure effect, and safety and tolerability.
RESULTS: The Safety Analysis Set (SAS) included 41 patients (<4 years; mean maximum dose, 3.5 mg/day) and 203 patients (4-<12 years; mean maximum dose, 5.3 mg/day); 24-month retention rates were 35.7% (n = 5/14) and 42.0% (n = 47/112), respectively. In the Full Analysis Set, during Months 1-3, median percent reductions in seizure frequency were 33.3% (n = 8 [<4 years]) and 26.0% (n = 32 [4-<12 years]), and seizure-freedom rates were 12.5% in both groups (n = 1/8 and n = 4/32); patient numbers were low at later time points. Most patients showed improvements in seizure control (45.9% [<4 years] versus 52.4% [4-<12 years]) or no change (45.9% versus 34.5%) (SAS). Treatment-emergent adverse events (TEAEs) were reported in 12 (<4 years: 29.3%; most common, irritability [7.3%]) and 64 patients (4-<12 years: 31.5%; most common, aggression [6.9%]).
CONCLUSIONS: Perampanel was generally well tolerated with <21% of TEAEs leading to withdrawal at 24 months, had favorable retention rates (≥50% and >35% at 12 and 24 months, respectively), and sustained efficacy in pediatric patients during routine clinical care.

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.

UNASSIGNED: There is currently a lack of studies examining the long-term therapeutic effectiveness of the third-generation anti-sezure medication, perampanel (PER), for focal-onset seizures (FOS), particularly in Chinese patients with sleep-related epilepsy (SRE). Additionally, the appropriate dosage, plasma concentration, and the relationship between dose and plasma concentration of PER in Chinese patients are still uncertain.
UNASSIGNED: A prospective, single-center, 24-month observational study was conducted in patients diagnosed with FOS, with a focus on patients with SRE. Changes in seizure frequency from baseline, adverse events, and retention rates were analyzed at 12 and 24 months following the start of the treatment. Tolerability was evaluated based on adverse events and discontinuation profiles. PER plasma concentrations were used to assess dose-concentration-response relationships.
UNASSIGNED: A total of 175 patients were included (median age: 25 years; range: 4-72 years; 53. 1% males and 46.9% females), with the SRE population accounting for 49. 1% (n = 86). The patients diagnosed with SRE showed considerably higher response rates than those who did not have this diagnosis (p = 0.025, odds ratio = 3.8). Additionally, the SRE group adhered better to PER treatment (r = 0.0009). Patients with a shorter duration of epilepsy (median: 3 years; range:2-7 years) demonstrated a more favorable therapeutic response to PER (p = 0.032). Throughout the administration of maintenance doses, among the entire FOS population, the concentration of PER (C0) ranged between 101.5 and 917.4 ng/mL (median, 232.0 ng/mL), and the mean plasma concentration of PER in the responders was 292.8 ng/mL. We revealed a linear relationship between PER dose and plasma concentration, regardless of whether PER was used as monotherapy or add-on therapy. The retention rates were 77.7% and 65. 1% at 12 and 24 months, respectively. Drug-related adverse events occurred in 45.0% of the patients and were mostly manageable.
UNASSIGNED: PER effectively reduced seizure frequency in Chinese patients with FOS, particularly in those with SRE, over a 24-month period. The treatment was well-tolerated and had a clear linear dose-plasma concentration relationship.

UNASSIGNED: Since 2019, Perampanel (PER) has been endorsed in China as an adjunctive treatment for focal seizures, both with and without impaired awareness, and for the transition from focal to bilateral tonic-clonic seizures. Limited research exists regarding the efficacy of PER in treating post-stroke epilepsy (PSE) in China. Empirical studies are essential to guide treatment protocols. We conducted a retrospective study to assess the efficacy and tolerability of PER in 58 PSE patients treated between October 2019 and July 2023.
UNASSIGNED: This study encompassed 58 patients with PSE, treated with PER either as monotherapy or as part of adjunctive therapy, and underwent follow-up for a minimum duration of 6 months. The study assessed changes in seizure frequency, adverse events (AEs), drug retention rate, maintenance dose, and adverse reactions following PER treatment.
UNASSIGNED: The study included 58 PSE patients, with 60.3% males and 39.7% females, ranging in age from 18 to 89, mostly within the 61-70 age group. Ischemic strokes constituted 58.6% of cases, while hemorrhagic strokes accounted for 41.4%. Focal seizures, either with or without impaired awareness, were noted in 62.1% of patients, and a transition from focal to bilateral tonic-clonic seizures was seen in 32.8%. The retention rates for PER at 3 and 6 months stood at 94.8% and 84.5% respectively, and the most commonly administered maintenance dose was 4 mg/day (41.28%). In the adjunctive therapy group, efficacy rates were 66.7% at 3 months and 78.6% at 6 months, compared to 80.0% at 3 months and 85.7% at 6 months in the monotherapy group. In the efficacy analysis, with a criterion of ≥50% reduction in seizure frequency, the overall efficacy rates at 3 and 6 months were 69.1% and 79.6%, respectively. Adverse reactions occurred in 46.6% of patients, primarily involving irritability and somnolence (both 27.6%), with no marked difference in incidence between the adjunctive and monotherapy groups (P > 0.05).
UNASSIGNED: PER exhibits favorable efficacy and tolerability in Chinese PSE patients, possibly at lower doses.