Efficacy and tolerability of adjuvant perampanel: an Australian multicenter real-world observational study in refractory focal and generalized epilepsy syndromes

Sagar, Parveen; Wawryk, Olivia; Vogrin, Sara; Whitham, Emma M.; Kiley, Michelle; Frasca, Joseph; Carne, Ross; Seneviratne, Udaya; Cook, Mark; Lawn, Nicholas; Nikpour, Armin; D’Souza, Wendyl

doi:10.1016/j.yebeh.2021.107935

Cited by 9 publications

(17 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To our knowledge, only six studies have previously investigated the use of PER specifically in PWE with IGE in clinical practice, [22][23][24][25] three of which were included in PERMIT. [22][23][24] The fourth was an Australian multicenter, retrospective cohort study, which demonstrated that PER was effective and well tolerated as a late adjunctive therapy in 387 PWE with drug-resistant IGE, focal epilepsy, or developmental epileptic encephalopathy treated for a median of 12 months.…”

Section: F I G U R Ementioning

confidence: 99%

“…17,18 Clinical practice studies provide evidence on how a drug performs when used outside the relative restrictions of clinical trials, [19][20][21] but real-world evidence on the use of PER to specifically treat IGE is currently limited. [22][23][24][25][26][27] The PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study included approximately 5200 people with focal and generalized epilepsy who were treated with PER in clinical practice. 28 The purpose of this study was to assess the real-world effectiveness and safety/ tolerability of PER when used to treat people with IGE included in PERMIT.…”

Section: Introductionmentioning

confidence: 99%

“…Approval of PER for the treatment of GTCS in IGE was based on the results of one phase 3, randomized, double‐blind, placebo‐controlled trial 17,18 . Clinical practice studies provide evidence on how a drug performs when used outside the relative restrictions of clinical trials, 19–21 but real‐world evidence on the use of PER to specifically treat IGE is currently limited 22–27 …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Perampanel for the treatment of people with idiopathic generalized epilepsy in clinical practice

Trinka

Alsaadi²,

Goji

et al. 2023

Epilepsia

View full text Add to dashboard Cite

ObjectiveThis study was undertaken to evaluate perampanel (PER) when used under real‐world conditions to treat people with idiopathic generalized epilepsy (IGE) included in the PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study.MethodsThe multinational, retrospective, pooled analysis PERMIT explored the use of PER in people with focal and generalized epilepsy treated in clinical practice across 17 countries. This subgroup analysis included PERMIT participants with IGE. Time points for retention and effectiveness measurements were 3, 6, and 12 months (last observation carried forward, defined as "last visit," was also applied to effectiveness). Effectiveness was evaluated by seizure type (total seizures, generalized tonic–clonic seizures [GTCS], myoclonic seizures, absence seizures) and included ≥50% responder rate and seizure freedom rate (defined as no seizures since at least the previous visit). Safety/tolerability was monitored throughout PER treatment and evaluated by documenting the incidence of adverse events (AEs), including psychiatric AEs and those leading to treatment discontinuation.ResultsThe Full Analysis Set included 544 people with IGE (51.9% women, mean age = 33.3 years, mean epilepsy duration = 18.1 years). At 3, 6, and 12 months, 92.4%, 85.5%, and 77.3% of participants were retained on PER treatment, respectively (Retention Population, n = 497). At the last visit, responder and seizure freedom rates were, respectively, 74.2% and 54.6% (total seizures), 81.2% and 61.5% (GTCS), 85.7% and 66.0% (myoclonic seizures), and 90.5% and 81.0% (absence seizures) (Effectiveness Population, n = 467). AEs occurred in 42.9% of patients and included irritability (9.6%), dizziness/vertigo (9.2%), and somnolence (6.3%) (Tolerability Population, n = 520). Treatment discontinuation due to AEs was 12.4% over 12 months.SignificanceThis subgroup analysis of the PERMIT study demonstrated the effectiveness and good tolerability of PER in people with IGE when administered under everyday clinical practice conditions. These findings are in line with clinical trial evidence, supporting PER's use as broad‐spectrum antiseizure medication for the treatment of IGE.

show abstract

Section: F I G U R Ementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Perampanel for the treatment of people with idiopathic generalized epilepsy in clinical practice

Trinka

Alsaadi²,

Goji

et al. 2023

Epilepsia

View full text Add to dashboard Cite

show abstract

“…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.…”

unclassified

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

et al. 2023

View full text Add to dashboard Cite

Objectives: The aim of this study was to systematically review the efficacy and tolerability of perampanel (PER) when used as add-on treatment or monotherapy in patients with epilepsy aged 12 years and older in routine clinical practice.Methods: Electronic and clinical trials databases were searched for observational studies of PER published up to 1 March 2022. The outcomes of interest were responder rates, adverse effects (AEs), and withdrawal rates. Subgroup analyses were performed to explore the potential factors that might affect the efficacy and safety of PER usage.Results: A total of 56 studies, which included 10,688 patients, were enrolled. The results showed that after 3, 6, and 12 months of PER treatment, the pooled 50% responder rates in patients with epilepsy were 50.0% (95% CI: 0.41–0.60), 44.0% (95% CI: 0.38–0.50), and 39.0% (95% CI: 0.31–0.48), respectively, and the pooled seizure-free rates were 24.0% (95% CI: 0.17–0.32), 21.0% (95% CI: 0.17–0.25), and 20.0% (95% CI: 0.16–0.24), respectively. Subgroup analyses revealed that the efficacy of PER could be affected by the way in which PER is administrated. Patients in the groups where PER was used as the first add-on, primary monotherapy, or combined with non–enzyme-inducing AEDs (non-EIAEDs) displayed a high 50% responder rate and seizure-free rate when compared with those in the late add-on, conversion therapy, or combined with the EIAEDs groups, respectively. Furthermore, the incidences of AEs at 3, 6, and 12 months of PER treatment were 46% (95% CI: 0.38–0.55), 52.0% (95% CI: 0.43–0.60), and 46.0% (95% CI: 0.40–0.52), respectively. The withdrawal rates due to AEs were 8.0% (95% CI: 0.06–0.11), 16.0% (95% CI: 0.13–0.20), and 16% (95% CI: 0.11–0.21) at 3, 6, and 12 months of PER treatment, respectively. Subgroup analyses showed a higher withdrawal rate in the rapid (30%, 95% CI: 0.22–0.38) than in the slow (12%, 95% CI: 0.06–0.18) titration group.Conclusion: Altogether, PER was effective and could be fairly tolerated in both short-term and long-term usage in patients with epilepsy in routine clinical practice. Furthermore, PER appeared to be more effective when PER was used as the first add-on, monotherapy, or concomitant with non-EIAEDs.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022384532.

show abstract

“…The efficacy and tolerability profiles of perampanel in Asian adult patients appears to be similar to that in non-Asian populations [6,7]. Data for paediatric and adolescent patients were collected in randomized trials [8][9][10][11][12] and real-world data are also available [13][14][15][16]; however, there is a scarcity of information from large samples of adolescents treated in routine clinical settings in Asia. Therefore, we conducted a large-scale, prospective, observational, post-marketing study (PMS) to evaluate the safety and efficacy of perampanel in adolescent patients (aged 12-17 years) with drug-resistant, refractory epilepsy in real-world settings in Japan.…”

mentioning

confidence: 99%

Real‐world evaluation of perampanel effectiveness in Japanese adolescents with epilepsy

Inoue¹,

Sumitomo²,

Matsutani³

et al. 2022

Epileptic Disorders

View full text Add to dashboard Cite

Objective. Real‐world data from adolescents treated with perampanel in a routine clinical setting are lacking in Japan. We evaluated the safety and efficacy of perampanel for adolescent patients (aged 12‐17 years) with drug‐resistant, refractory epilepsy in real‐world settings. Methods. This was a large‐scale, prospective, observational post‐marketing study, with a 104‐week observation period. Safety was assessed by monitoring adverse effects (adverse drug reactions). For efficacy assessments, seizure frequency was compared between the four weeks immediately prior to the last observation and the four weeks before the commencement of perampanel. Results. In total, 519 patients were enrolled;505 and 484 patients were included in the safety and efficacy analysis sets, respectively. The mean age was 14.4 years. The mean daily dose of perampanel was 4.4 mg/day. The main reasons for discontinuation at 104 weeks were adverse events (48.4%) and inadequate efficacy (46.8%). The retention rate at 104 weeks was 50.5%. Adverse effect and severe adverse effect incidences were 42.2% and 1.8%, respectively. The most common adverse effects were somnolence (13.5%), irritability (8.5%), dizziness (5.1%), and agitation (4.8%). There were significant differences in the occurrence of adverse effects between the initial titration interval of <2 weeks and 2‐4 weeks (odds ratio=0.441, p=0.029) and 4‐8 weeks (odds ratio=0.462, p=0.027). The median percent change in seizure frequency at the last observation carried forward was –50.0 for focal aware seizures with motor signs, –73.3 for focal aware seizures without motor signs, –28.6 for focal impaired awareness seizures, –62.6 for focal to bilateral tonic‐clonic seizures, and –20.0 for generalized tonic‐clonic seizures. Significance. In adolescent patients, perampanel was well tolerated and efficacious in reducing seizure frequency. No unexpected safety issues were observed, and slow titration may reduce the incidence of adverse effects.

show abstract

Efficacy and tolerability of adjuvant perampanel: an Australian multicenter real-world observational study in refractory focal and generalized epilepsy syndromes

Cited by 9 publications

References 47 publications

Perampanel for the treatment of people with idiopathic generalized epilepsy in clinical practice

Perampanel for the treatment of people with idiopathic generalized epilepsy in clinical practice

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

Real‐world evaluation of perampanel effectiveness in Japanese adolescents with epilepsy

Contact Info

Product

Resources

About