Tolerability Of Perampanel Research Articles

Perampanel in post-stroke epilepsy: Clinical practice data from the PERampanel as Only Concomitant antiseizure medication (PEROC) study

IntroductionPost-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy. Nevertheless, there is limited evidence regarding the clinical profile of antiseizure medications (ASMs) in PSE. This study aims to evaluate the 12-month effectiveness and tolerability of perampanel (PER) used as only add-on treatment in patients with PSE in a real-world setting. MethodsWe performed a subgroup analysis of PSE patients included in a previous retrospective, longitudinal, multicentre observational study on adults. Treatment discontinuation, seizure frequency and adverse events were collected at 3, 6 and 12 months. Sub-analyses by early (≤1 previous ASM) or late PER add-on were also conducted. ResultsOur analysis included 56 individuals with PSE, characterized by varying initial treatment modalities and timeframes relative to disease onset. We found notable retention rates (92.8%, 83.7%, and 69% at 3, 6, and 12 months), with treatment withdrawal mainly due to poor tolerability. One year after PER introduction, seizure frequency significantly reduced, with a responder rate (≥50% reduction) of 83.9% and a seizure-free rate of 51.6%. Adverse events occurred in 25 (46.3%) patients, mainly dizziness, irritability, and behavioural disorders. No major statistical differences were found between early (30 patients, 53.6%) and late add-on groups, except for a higher 6-month responder rate in the early add-on group. ConclusionAdjunctive PER was effective and well-tolerated in patients with PSE in a real-world setting. Perampanel demonstrated good efficacy and safety as both early and late add-on treatment, making it a compelling option for this unique patient population.

Efficacy and tolerability of perampanel in pediatric patients with Dravet syndrome.

In 1978, Charlotte Dravet first described a form of epilepsy termed Dravet syndrome (DS). It is a form of genetic epilepsy with early-onset, intractable epilepsy episodes, and neurodevelopmental delay. In children, DS can lead to refractory seizures that are resistant to standard therapy. Recently, perampanel (PER) was approved as an antiepileptic drug for patients as young as 4 years old. The medical records were retrospectively reviewed and patients with DS who used PER were included in this study. The diagnosis was established using whole-exome sequencing, and the collected data included the patients' demographic characteristics, seizure pattern, PER dosage, laboratory and imaging findings. This study included 18 pediatric patients with a clinical diagnosis of DS. The mean age of PER initiation was 7.67±3.865. Most patients had two types of seizures (61.1%) followed by three types (22.2%), with generalized tonic-clonic being the most frequently reported type of seizure. The mean efficacy of PER was 29.17%±29.368%, and only one patient had an efficacy of 100%. Moreover, patients aged 8 years and younger presented with higher efficacy than those who were older (49.17%±34.120% vs. 19.17%±21.829%, P=0.03). This study presented supporting evidence of the promising therapeutic effect of PER among patients with DS. PER can be considered one of the treatment options for this group of patients. However, several patients presented with unfavorable side effects that led to medication cessation. Future multicenter studies are required to explore further treatment options for patients with DS.

A 3.5-year clinical experience with perampanel for refractory epilepsy.

This study aimed to evaluate the efficacy and tolerability of perampanel, which was used in a cohort of patients with refractory epilepsy for up to 3.5 years in a real-world setting in Saudi Arabia. Data from the medical records of patients treated with perampanel between March 13th, 2017, and September 6th, 2020, at neurology clinics at King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh and Jeddah, Saudi Arabia, was collected. The Liverpool Adverse Events Profile (LAEP) scale was also used to measure the adverse effects of perampanel. Of the 75 included patients, 66.7% responded to perampanel at the last follow-up, including 22.7% seizure-free for at least the last six months, and 44% of patients responded with a ≥ 50% reduction in seizure frequency from baseline. The overall incidence of adverse effects that led to perampanel discontinuation was 13.3%; the most common adverse effect was aggressive behavior followed by sedation. Pre-existing psychiatric comorbidity was significantly associated with the incidence of psychiatric and behavioral adverse effects on perampanel (p = 0.0206). The mean score of LEAP was 40. The most frequently rated adverse effects in LEAP were "feelings of anger and aggression to others", "nervousness and/or agitation" and "sleepiness". The efficacy and tolerability of perampanel were dose-dependent. Dose 6 mg/day was the most frequently used dose that was taken by about one-third of patients at their last visit. Perampanel was effective as an adjunctive treatment for intractable seizures, with a responder rate of 66.7%. The long-term tolerability of perampanel was generally good. Aggressive behavior was the most common reason for perampanel discontinuation. Patients should be counseled and monitored for these adverse effects, particularly those with a history of previous psychiatric and behavioral problems.

PerSurge (NOA-30) phase II trial of perampanel treatment around surgery in patients with progressive glioblastoma

BackgroundGlioblastoma is the most frequent and a particularly malignant primary brain tumor with no efficacy-proven standard therapy for recurrence. It has recently been discovered that excitatory synapses of the AMPA-receptor subtype form between non-malignant brain neurons and tumor cells. This neuron-tumor network connectivity contributed to glioma progression and could be efficiently targeted with the EMA/FDA approved antiepileptic AMPA receptor inhibitor perampanel in preclinical studies. The PerSurge trial was designed to test the clinical potential of perampanel to reduce tumor cell network connectivity and tumor growth with an extended window-of-opportunity concept.MethodsPerSurge is a phase IIa clinical and translational treatment study around surgical resection of progressive or recurrent glioblastoma. In this multicenter, 2-arm parallel-group, double-blind superiority trial, patients are 1:1 randomized to either receive placebo or perampanel (n = 66 in total). It consists of a treatment and observation period of 60 days per patient, starting 30 days before a planned surgical resection, which itself is not part of the study interventions. Only patients with an expected safe waiting interval are included, and a safety MRI is performed. Tumor cell network connectivity from resected tumor tissue on single cell transcriptome level as well as AI-based assessment of tumor growth dynamics in T2/FLAIR MRI scans before resection will be analyzed as the co-primary endpoints. Secondary endpoints will include further imaging parameters such as pre- and postsurgical contrast enhanced MRI scans, postsurgical T2/FLAIR MRI scans, quality of life, cognitive testing, overall and progression-free survival as well as frequency of epileptic seizures. Further translational research will focus on additional biological aspects of neuron-tumor connectivity.DiscussionThis trial is set up to assess first indications of clinical efficacy and tolerability of perampanel in recurrent glioblastoma, a repurposed drug which inhibits neuron-glioma synapses and thereby glioblastoma growth in preclinical models. If perampanel proved to be successful in the clinical setting, it would provide the first evidence that interference with neuron-cancer interactions may indeed lead to a benefit for patients, which would lay the foundation for a larger confirmatory trial in the future.Trial registrationEU-CT number: 2023-503938-52-00 30.11.2023.

Perampanel as only add-on epilepsy treatment in elderly: A subgroup analysis of real-world data from retrospective, multicenter, observational study

IntroductionDrug management of epilepsy in the elderly presents unique but data on this population are scarce. This study aimed to assess the effectiveness and tolerability of perampanel (PER) used as only add-on to a background anti-seizure medication (ASM) in the elderly in a real-world setting. MethodsWe performed a subgroup analysis of patients aged ≥65 years included in a previous 12-month multicenter study on adults. Treatment discontinuation, seizure frequency, and adverse events were recorded at 3, 6 and 12 months after PER introduction. Sub-analyses by early (≤1 previous ASM) or late PER add-on were also conducted. ResultsThe sample included 65 subjects (mean age: 75.7 ± 7.2 years), with mainly focal (73.8%) epilepsy. The mean PER daily dose was ≈4 mg during all follow-up. Retention rates at 3, 6, and 12 months were 90.5%, 89.6%, and 79.4%ly. The baseline median normalized per 28-day seizure number significantly decreased at 3-, 6- and 12-month visits. One year after PER introduction, the responder rate (≥50% reduction in baseline seizure frequency) was 89.7%, with a seizure freedom rate of 72.4%. Adverse events occurred in 22 (34.9%) patients with dizziness and irritability being the most frequent. No major differences between early (41 patients, 63.1%), and late add-on groups were observed. ConclusionAdjunctive PER was effective and well-tolerated when used as only add-on treatment in elderly people with epilepsy in clinical practice, thus representing a suitable therapeutic option in this age category.

Plasma Concentration, Efficacy, and Tolerability of Perampanel in Chinese Pediatric Patients with Epilepsy: Real-World Clinical Experience.

Information on the efficacy and plasma concentration of perampanel (PER) in Chinese pediatric patients with epilepsy is limited. Therefore, this real-world retrospective study aimed to assess the efficacy, tolerability, and plasma concentration of the maximum dose of PER for epilepsy treatment in Chinese pediatric patients. A total of 107 pediatric patients from 2 hospitals in China were enrolled in this study. The plasma concentration of PER was determined using ultrahigh-performance liquid chromatography. The primary efficacy endpoint was the seizure reduction rate after PER treatment at the last follow-up. The response rate to PER therapy was 59.8% (64/107). The authors observed that patients younger than 6 years of age (n = 49) showed a significantly lower concentration-to-dose ratio than patients with ages between 6 and 14 years (n = 58) (2.2 ± 1.7 vs. 3.0 ± 1.8 mcg·mL -1 ·kg·mg -1 , respectively; P < 0.05). Patients who received enzyme-inducing antiseizure medication had significantly lower concentration-to-dose ratios than those who did not receive enzyme-inducing antiseizure medication (EIASM) (2.1 ± 1.8 vs. 3.1 ± 2.0 mcg·mL -1 ·kg·mg -1 , P < 0.05). A total of 37 patients (34.6%) reported treatment adverse events. Patients with somnolence and irritability had a significantly higher PER plasma concentration than the "no treatment-emergent adverse effect" groups ( P < 0.05). PER is an effective and well-tolerated treatment option for patients with epilepsy. To ensure the clinical efficacy and safety of PER in pediatric patients, it is necessary to monitor its plasma concentrations.

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

ObjectiveTo 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. MethodsThe 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). ResultsFull 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). ConclusionIn 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.

Efficacy and safety of perampanel monotherapy in patients with focal-onset seizures:A real-world experience in eastern China

ObjectiveTo assess the effectiveness and tolerability of perampanel (PER) monotherapy in real-world practice for the treatment of focal-onset seizures (FOS) in eastern China. MethodThis is a single-center, retrospective study of patients with FOS, aged ≥ 4 years, who had been prescribed PER as monotherapy. Outcomes included retention, seizure-free, and responder rates at 3, 6 and 12 months and adverse events (AEs) throughout the follow-up period. The efficacy and AEs of PER monotherapy in patients with aged < 14 years old and ≥ 14 years old were also compared. ResultsSixty-seven patients with FOS who received PER monotherapy and completed a one-year follow-up were included in the analysis. The median maintenance dose was 4 mg. Modified intent-to-treat analysis demonstrated that the retention rates of PER monotherapy at follow-up of 3, 6 and 12months were 75%, 70% and 63%, respectively. At the same points, seizure-free rates of PER monotherapy were 69%, 63% and 52%, and responder rates were 69%, 66% and 61%, respectively. Patients with sleep-related seizures had higher seizure-free rates at 12 months of follow-up. No significant difference in seizure-free and responder rates was found between the aged < 14 years old and the aged ≥ 14 years old. Twenty-one patients (31.3%) had AEs and five patients discontinued using PER because of intolerant AEs. Common AEs were dizziness, irritability and somnolence. The AEs rate in patients < 14 years was 17.9%, significantly lower than patients ≥ 14 years. ConclusionsOur findings revealed the real-world data of patients in eastern China with FOS using PER as monotherapy. Patients had good retention, seizure-free and responder rates, and relatively low AEs rate at a low dose of PER treatment.

Efficacy, Tolerability, and Safety of Treatment With Perampanel in Pediatric Patients With Epilepsy Aged ≥4 Years: A Real-Life Observational Study.

Purpose: The safety and effectiveness of perampanel in clinical settings involving Chinese pediatric patients are limited, as perampanel has only recently been approved for use in China, in September 2019. We aimed to evaluate the efficacy and tolerability of perampanel as an adjunctive therapy for pediatric patients with epilepsy aged ≥ 4 years in Xinjiang, Northwest China. Methods: Efficacy was assessed by measuring changes in seizure frequency at 3-, 6-, and 12-month follow-up compared with baseline. The baseline was 3 months before the addition of perampanel, and the seizure frequency was based on the patients' seizure diary. The safety and tolerability depended on the type and frequency of any adverse event during epilepsy treatment across all pediatric patients. Results: Overall, 67 pediatric patients from 2 different hospitals were enrolled in the study. Among the pediatric patients with seizures during the baseline period, the effective rates for all seizure types at 3, 6, and 12 months were 59.1%, 58.7%, and 57.4%, respectively. During perampanel treatment, 34 patients (50.7%) experienced at least 1 adverse reaction. Conclusion: Overall, this real-world retrospective study of pediatric patients validated that perampanel is an effective treatment option as an adjunctive therapy among pediatric patients with epilepsy aged ≥4 years.

Perampanel outcomes at different stages of treatment in people with focal and generalized epilepsy treated in clinical practice: Evidence from the PERMIT study.

The PERMIT study is the largest pooled analysis of perampanel (PER) clinical practice data conducted to date. This post-hoc analysis of PERMIT investigated the effectiveness, safety and tolerability of PER when used as early add-on therapy (after failure of one or two previous antiseizure medications) in comparison with late add-on therapy (after failure of three or more previous antiseizure medications). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness was assessed by seizure type (total seizures, focal seizures, generalized tonic-clonic seizures [GTCS]) and assessments included seizure freedom rate and responder rate. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs. The Full Analysis Set included 1184 and 2861 PWE treated with PER as early and late add-on therapy, respectively. Compared to the late add-on subgroup, the early add-on subgroup was characterized by later mean age at epilepsy onset, shorter mean duration of epilepsy, lower rates of intellectual disability and psychiatric comorbidity, and lower frequency of seizures per month, suggesting a less severe form of epilepsy in this subgroup. After 12 months, retention was significantly higher in the early versus late add-on subgroup (67.7% vs. 62.4%; p = 0.004). At the last visit, responder rates in the early versus late add-on subgroup were significantly higher for total seizures (68.2% vs. 39.3%; p < 0.001), focal seizures (65.0% vs. 36.8%; p < 0.001) and GTCS (83.7% vs. 67.2%; p < 0.001), as were seizure freedom rates (total seizures, 35.9% vs. 11.9% [p < 0.001]; focal seizures, 29.4% vs. 8.7% [p < 0.001]; GTCS, 69.0% vs. 48.1% [p < 0.001]). Incidence of AEs was significantly lower in the early versus late add-on subgroup (42.1% vs. 54.7%; p < 0.001), as was the rate of discontinuation due to AEs over 12 months (15.0% vs. 18.1%; p = 0.031). This study demonstrated that PER was effective and generally well tolerated when initiated as early or late add-on therapy, but it was significantly more effective and better tolerated when initiated early. These findings support PER's use as a broad-spectrum, early add-on therapy for use in PWE with focal and generalized seizures.

Efficacy and Tolerability of Perampanel in Brain Tumor-Related Epilepsy: A Systematic Review

(1) Background: Epilepsy is a frequent comorbidity in patients with brain tumors, in whom seizures are often drug-resistant. Current evidence suggests that excess of glutamatergic activity in the tumor microenvironment may favor epileptogenesis, but also tumor growth and invasiveness. The selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist perampanel (PER) was demonstrated to be efficacious and well-tolerated in patients with focal seizures. Moreover, preclinical in vitro studies suggested a potential anti-tumor activity of this drug. In this systematic review, the clinical evidence on the efficacy and tolerability of PER in brain tumor-related epilepsy (BTRE) is summarized. (2) Methods: Five databases and two clinical trial registries were searched from inception to December 2022. (3) Results: Seven studies and six clinical trials were included. Sample size ranged from 8 to 36 patients, who received add-on PER (mean dosage from 4 to 7 mg/day) for BTRE. After a 6-12 month follow-up, the responder rate (% of patients achieving seizure freedom or reduction ≥ 50% of seizure frequency) ranged from 75% to 95%, with a seizure freedom rate of up to 94%. Regarding tolerability, 11-52% of patients experienced non-severe adverse effects (most frequent: dizziness, vertigo, anxiety, irritability). The retention rate ranged from 56% to 83%. However, only up to 12.5% of patients discontinued the drug because of the adverse events. (4) Conclusions: PER seems to be efficacious, safe, and well-tolerated in patients with BTRE. Further randomized studies should be conducted in more homogeneous and larger populations, also evaluating the effect of PER on tumor progression, overall survival, and progression-free survival.

Perampanel in Brain Tumor-Related Epilepsy: A Systematic Review

Brain tumor-related epilepsy (BTRE) is a common comorbidity in patients with brain neoplasms and it may be either the first symptom or develop after the tumor diagnosis. Increasing evidence suggests that brain tumors and BTRE share common pathophysiological mechanisms. Glutamatergic mechanisms can play a central role in promoting both primary brain tumor growth and epileptogenesis. Perampanel (PER), which acts as a selective antagonist of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, may play a role both in the reduction in tumor growth and the control of epileptiform activity. This systematic review aimed to summarize the pre-clinical and clinical evidence about the antitumor properties, antiseizure effects and tolerability of PER in BTRE. Eight pre-clinical and eight clinical studies were identified. The currently available evidence suggests that PER can be an effective and generally well-tolerated therapeutic option in patients with BTRE. In vitro studies demonstrated promising antitumor activity of PER, while no role in slowing tumor progression has been demonstrated in rat models; clinical data on the potential antitumor activity of PER are scarce. Additional studies are needed to explore further the effects of PER on tumor progression and fully characterize its potentialities in patients with BTRE.

Perampanel Monotherapy for Focal and Generalized Epilepsy in Clinical Practice

Objectives. To investigate the effectiveness, safety, and tolerability of perampanel (PER) when used as monotherapy to treat focal or generalized epilepsy in everyday clinical practice, using data from the PERMIT study. Methods. PERMIT was a pooled analysis of 44 real-world studies from 17 countries, in which people with focal and generalized epilepsy were treated with PER. This post hoc analysis included people with epilepsy (PWE) from PERMIT who were treated with PER monotherapy at baseline. Retention and effectiveness were assessed after 3, 6, and 12 months. Effectiveness assessments included ≥50% responder rate and seizure freedom rate (no seizures since at least the prior visit). Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs. Results. Overall, 268 PWE were treated with PER monotherapy at baseline. Retention was assessed for 168 PWE, effectiveness for 183 PWE, and safety and tolerability for 197 PWE. Retention rates were 91.1%, 87.3%, and 73.3% at 3, 6, and 12 months, respectively. At 12 months, responder rates were 84.2% overall, 82.9% in PWE with only focal-onset seizures at baseline, and 88.0% in those with only generalized-onset seizures at baseline; corresponding freedom rates were 62.9%, 57.7%, and 80.0%, respectively. AEs were reported for 45.2% of PWE. The most frequently reported AEs (≥5% of PWE) were dizziness/vertigo (16.8%), irritability (11.2%), somnolence (9.1%), and depression (6.6%). Over 12 months, 13.7% discontinued due to AEs. Conclusions. PER was effective when used as monotherapy in clinical practice, particularly in those with generalized-onset seizures, and was generally well tolerated.

Therapeutic drug monitoring of perampanel in children diagnosed with epilepsy: Focus on influencing factors on the plasma concentration-to-dose ratio.

This study aimed to investigate the efficacy and tolerability of perampanel (PER) therapy and to optimize a specific plasma reference range for PER in children. Another major aim was to evaluate the potential determinators of PER concentration. Concentrations obtained from 80 children were analyzed for routine therapeutic drug monitoring (TDM) between 2021 and 2022. We retrospectively reviewed the clinical data of these patients and assessed the efficacy at 3 months after treatment initiation. Trough concentration-to-dose ratio (C0 /Dose ratio) of PER was compared among patients on various potential influencing factors. A 3-month PER therapy produced a ≥50% reduction in seizure frequency in 58.8% of patients. Twelve patients reported at least one adverse effect (AE), mainly dizziness. The monitoring data showed that the median C0 was 325.5ng/mL. Under maintenance dosages, approximately 75% of the C0 values were 180.0-610.0ng/mL. The C0 /Dose ratio in patients aged 1 to <4 was significantly lower by twofold than in those aged 4 to ≤12 years (P= 0.001). Enzyme-inducing ASMs (EIASMs) decreased the C0 /Dose ratio of PER by 25.9% (P= 0.165). In addition, seizure frequency reduction in responders was achieved at a median PER C0 value of 357 ng/mL, which was similar to the value of 314 ng/mL found in nonresponders (P= 0.288). No significant difference was found in PER C0 values between patients with and without AEs (P= 0.082). In this study, PER treatment showed acceptable efficacy and tolerance in Chinese children with epilepsy. Contributing factors like age to variable C0 /Dose ratios were identified, and complex PER-ASMs interactions were observed. Notably, the reference range, that is, 180.0-610.0ng/mL, for routine PER monitoring may be more applicable for them. Routine TDM should be considered a positive attempt to manage the effectiveness and safety of PER.

Perampanel and childhood absence epilepsy: A real life experience.

ObjectivesThe aim of our study was to evaluate the effectiveness and tolerability of perampanel (PER) as first add-on and as second line monotherapy in subjects with childhood absence epilepsy.MethodsOur sample consisted of 20 patients with childhood absence epilepsy, aged between 8 and 10, already in therapy with a first antiseizure medication with incomplete seizure control. PER was added as first add-on in a dose ranging from 3 to 8 mg/die with 1- 2 mg/week increments. The patients that were seizure-free were shifted to a PER monotherapy. All patients underwent a standardized neuropsychological evaluation in order to assess non-verbal intelligence and executive functions before adding PER and after 6 months of drug therapy. All parents completed two questionnaires, in order to assess the emotional-behavioral problems and parental stress.Results15/20 patients responded to add-on PER and were seizure-free, in 3/20 patients we observed a reduction of seizure frequency <50%, and in the 2 remaining patients the add-on therapy with PER did not lead to a reduction in seizures frequency from baseline. The patients who were seizure-free were switched to PER monotherapy. 9/15 patients remained seizure-free in monotherapy with PER. In the first month of therapy with PER 2/20 patients (10%) reported mild, transient side effects of irritability, headache and dizziness, which did not lead to discontinuation of therapy. Adjunctive treatment with PER did not negatively affect non-verbal intelligence, executive functions, emotional/behavioral symptoms of children and parental stress levels.SignificanceOur clinical experience in real life showed that PER appears to be effective in the control of absence seizures in childhood absence epilepsy, with a favorable tolerability profile. PER would seem effective on absence seizures even in monotherapy. Further studies with larger samples, longer follow-up and controlled vs. placebo (or other first choice antiseizure medications) are needed to confirm our data.

Use of perampanel in children with refractory epilepsy of genetic aetiology

Pathogenic mutations in refractory childhood epilepsy are being increasingly discovered. In this study, we analysed the efficacy and tolerability of perampanel as treatment for genetically-related refractory childhood epilepsy. This prospective study, conducted in China, included 50 patients with refractory epilepsy of genetic aetiology, who were treated with adjunctive perampanel therapy. Perampanel treatment was considered effective when the seizure frequency was reduced by >50%. Perampanel treatment was evaluated over at least nine months, from January 2020. A total of 184 paediatric patients with refractory epilepsy received addon perampanel therapy, and of these, 128 received treatment for ≥nine months and underwent genetic analysis. Fifty children were identified with pathogenic or likely pathogenic variants. A total of 24 different causative monogenic mutations were found, and the most common causative monogenic variants were observed in the SCN1A gene (n = 15). The mean maximal dose of perampanel was 3.4±1.2 mg/day in responders. The response rates to perampanel in children with genetically-related refractory epilepsy (n=50) were 68.0%, 58.0%, and 46.0% at three, six and nine months post-initiation, respectively. Adverse events were reported in 23 patients (46.0%) with genetic aetiology. Somnolence, ataxia, and irritability were the most common adverse events. The response rates to perampanel in children with pathogenic or likely pathogenic variants associated with Dravet syndrome, tuberous sclerosis, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes, Rett syndrome, and dentatorubral-pallidoluysian atrophy were high. A low maintenance dose of perampanel may be effective and well-tolerated as adjunctive treatment in children with refractory epilepsy of genetic aetiology.

Perampanel as adjunctive therapy in drug resistant epilepsy in adolescents and children waiting for epilepsy surgery: A multicenter observational study in Thailand

PurposeTo evaluate the effectiveness and tolerability of perampanel (PER) in real-world settings in patients between 1 month and 18 years of age with drug resistant epilepsy (DRE) waiting for epilepsy surgery. MethodsIn this multicenter study, patients between 1 month and 18 years of age with DRE treated with PER between January 2020 and June 2021 were selected. The study outcome was effectiveness of PER treatment reported as reduction in seizure frequency and seizure freedom rate. Effectiveness was assessed at 30, 60, 90, 120, 150 and 180 days after initiation of PER. Tolerability profiles were reported as adverse events according to the observations of the patients’ family members and physician. ResultsEighty-five patients treated with PER were included in the study. The mean initial dose and mean maximum dose of adjunctive PER was 2 mg/day and 5.8 mg/day, respectively. The mean seizure frequency (rate/week) was 41.3, 25.4, 18.9, 14.3, 11.2, 11.1 and 8.9 seizures at baseline, 30, 60, 90, 120, 150 and 180 days, respectively; the reduction in the mean seizure frequency at all timepoints was significant compared at the baseline (p<0.001). At 180 days, ≥75% seizure reduction was seen in 64.9% (37/57) of the patients and seizure freedom was achieved in 36.8% (21/57). Drowsiness, ataxia, and behavioral changes were the common adverse events observed, and these improved after the dose of PER was reduced. No discontinuation of PER was required due to side effects or intolerance. ConclusionIn real-world settings, PER is well tolerated and effective in seizure control in pediatric and adolescent patients with DRE.

Perampanel for the treatment of patients with myoclonic seizures in clinical practice: Evidence from the PERMIT study

PurposeTo investigate the effectiveness, safety and tolerability of perampanel (PER) in treating myoclonic seizures in clinical practice, using data from the PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study. MethodsPERMIT was a pooled analysis of 44 real-world studies from 17 countries, in which patients with focal and generalised epilepsy were treated with PER. This post-hoc analysis included patients with myoclonic seizures at baseline. Retention and effectiveness were assessed after 3, 6, and 12 months; effectiveness was additionally assessed at the last visit (last observation carried forward). Effectiveness assessments included responder rate (≥50% seizure frequency reduction from baseline) and seizure freedom rate (no seizures since at least the prior visit). Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs. Results156 patients had myoclonic seizures (59.0% female; mean age, 32.1 years; idiopathic generalised epilepsy, 89.1%; Juvenile Myoclonic Epilepsy, 63.1%; monthly median myoclonic seizure frequency [interquartile range], 1.7 [1.0–10.0]; mean [standard deviation] prior antiseizure medications, 2.9 [2.6]). Retention was assessed for 133 patients (mean time, 12.1 months), effectiveness for 142, and safety/tolerability for 156. Responder and seizure freedom rates were, respectively, 89.5% and 68.8% at 12 months, and 85.9% and 63.4% at the last visit. Incidence of AEs was 46.8%, the most frequent being dizziness/vertigo (19.2%), irritability (18.6%) and somnolence (9.6%). AEs led to discontinuation of 14.0% of patients over 12 months. ConclusionPER was associated with reduction in myoclonic seizure frequency in patients with myoclonic seizures treated in everyday clinical practice.

Efficacy, tolerability and safety of perampanel in population with pharmacoresistant focal seizures: A systematic review and meta-analysis

BackgroundFocal seizures are associated with various co-morbidities. Seizure disorders also affect the quality of life of the patients. A huge proportion of patients continue to have uncontrolled seizures despite the availability of numerous antiepileptic drugs. Novel therapeutic targets too, have failed to overcome this problem. Therefore, drugs acting on conventional targets are being explored. Perampanel is one such drug. The present study aimed to assess its efficacy, safety, and effect on quality of life and cognition in patients aged 12 years and above. MethodsDatabase search was conducted using keywords perampanel, partial seizures and randomized controlled trials (RCTs). Single and double blinded RCTs were included in the analysis. The primary outcomes assessed were 50% responder rate and seizure freedom rates. Secondary outcomes assessed were Improvement in Clinical Global Improvement for Change (CGI-C), number of patients who experienced adverse events, number of patients who withdrew from trials, adverse drug reaction (ADR) profile from Vigibase, long term safety, quality of Life (QoL) assessment and cognitive assessment, especially in adolescents. The Risk ratios (RR) were calculated for these parameters. Results24 full text articles were obtained out of a total 421 studies. From these seven double blind randomized controlled trials were included in the meta-analysis. Perampanel treated patients showed higher 50% responder rates than those treated with placebo. The Risk Ratios (RRs) were 1.39 [95% confidence interval (CI) 1.08–1.79], 1.83 [95% CI 1.51 – 2.22] and 1.81 [95% CI 1.45–2.27] for the 4 mg per day, 8 mg once daily and 12 mg once daily subgroups of perampanel respectively. The RRs for the seizure freedom rates were 4.52 [95% CI 1.30–15.73], 3.65 [95% CI 1.40–9.52] and 2.14 [95% CI 1.11–4.11] for 4 mg per day, 8 mg once daily and 12 mg once daily subgroups of perampanel respectively. There was a significantly higher risk of TEAEs with the 8 mg and 12 mg doses of perampanel as compared to that with placebo. Number of patients who withdrew from the trials due to adverse events was statistically significant in only the 12 mg subgroup of perampanel in comparison to that with placebo group. ConclusionPerampanel was observed to be an effective add on drug for treating pharmacoresistant focal seizures. The patients achieved higher 50% response rates and freedom from seizures with its use. Tolerability of perampanel was more at lower doses.

Effectiveness and tolerability of perampanel in сhildren and adolescents (own experience of Svt. Luka’s Institute of Child Neurology and Epilepsy)

Effectiveness and tolerability of perampanel in сhildren and adolescents (own experience of Svt. Luka’s Institute of Child Neurology and Epilepsy)