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.

Autor: Wheless J; University of Tennessee Health Science Center, Le Bonheur Children's Hospital, Memphis, TN, USA. Electronic address: jwheless@uthsc.edu., Wechsler RT; Idaho Comprehensive Epilepsy Center, Boise, ID, USA. Electronic address: wechsler5@me.com., Penovich P; Minnesota Epilepsy Group PA, St Paul, MN, USA. Electronic address: patricia.penovich@gmail.com., Segal E; Northeast Regional Epilepsy Group, Hackensack University Medical Center, Hackensack Meridian School of Medicine, Hackensack, NJ, USA. Electronic address: esegal@epilepsygroup.com., Chez M; Sutter Neuroscience Institute, Roseville, CA, USA. Electronic address: michael.chez@sutterhealth.org., Coppola A; Department of Neuroscience, Odontostomatological and Reproductive Sciences, Federico II University of Naples, Naples, Italy. Electronic address: antonietta.coppola1@gmail.com., Datta A; BC Children's Hospital, Vancouver, BC, Canada. Electronic address: anita.datta@cw.bc.ca., D'Souza W; Department of Medicine, St Vincent's Hospital Melbourne, The University of Melbourne, Victoria, Australia. Electronic address: wendyl@unimelb.edu.au., Najm I; Cleveland Clinic, Cleveland, OH, USA. Electronic address: imad.najm@gmail.com., Cappucci S; Eisai Inc, Nutley, NJ, USA. Electronic address: sheri_cappucci@eisai.com., Sainz-Fuertes R; Eisai Europe Ltd, UK. Electronic address: Ricardo_SainzFuertes@eisai.net., Villanueva V; Refractory Epilepsy Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain. Electronic address: vevillanuevah@yahoo.es.
Jazyk: angličtina
Zdroj: Epilepsy & behavior : E&B [Epilepsy Behav] 2023 Oct; Vol. 147, pp. 109369. Date of Electronic Publication: 2023 Aug 22.
DOI: 10.1016/j.yebeh.2023.109369
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JW has received grant support from Aquestive, Eisai, Greenwich, INSYS Inc., LivaNova, Mallinckrodt, Neurelis, NeuroPace, the Shainberg Foundation, and West; has served as a consultant for Aquestive, BioMarin, Eisai, Greenwich, Mallinckrodt, Neurelis, NeuroPace, Shire, Supernus, and Zogenix; and has received speaker bureau honoraria from BioMarin, Eisai, Greenwich, LivaNova, Mallinckrodt, and Supernus. RTW has been a clinical trial investigator for Aquestive, Biogen, Cavion, Cerevel, Eisai, Engage Pharma, Greenwich Biosciences, Lundbeck, Otsuka, Pfizer, SK Life Science, Sunovion, UCB Pharma, Xenon, and Zogenix; has served on advisory boards and/or carried out consulting work for Brain Sentinel, Cerevel, Eisai, Engage Pharma, Greenwich Biosciences, Lundbeck, Otsuka, SK Life Science, Sunovion, and UCB Pharma; has received speaker bureau honoraria from Aquestive, Eisai, Greenwich Biosciences, LivaNova, Neurelis, SK Life Science, Sunovion, and UCB Pharma; and is a member of the Epilepsy Study Consortium. PP has received Speakers Bureaus from Bureaus Jazz, Novartis, and UCB and advisory/consultant fees from LIVIS, Novartis and UCB. ES has received honoraria from Eisai, GW Pharma, Lundbeck, Neurelis, Nutricia, and Zogenix. MC has served as a consultant for, and has received grant support and/or speaker or advisory honoraria from, Aquestive, Eisai, GW Pharma, Mallinckrodt Zogenix, Marinus, Neurelis and UCB Pharma. AC has received speaker fees from EISAI and GW/Jazz pharmaceutical company and consultancy fees by GW/Jazz pharmaceutical Company, UCB, and BIAL. AD has no disclosures. WD’s salary is part-funded by The University of Melbourne and received honoraria and/or research funds from Eisai, GSK, LivaNova, Novartis, Pfizer, Sanofi, SciGen, Tilray, and UCB Pharma, and has equity interest in EpiMinder. IN received honoraria from Eisai. SC is an employee of Eisai. RSF is an employee of Eisai. VV has received honoraria and/or research funds from Angelini, Bial, Eisai, Jazz Pharmaceuticals, NewBridge, Novartis, Nutricia, Takeda, UCB Pharma and Zogenix.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: