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Observational Study
. 2025 Jun 7;272(7):449.
doi: 10.1007/s00415-025-13184-z.

Effectiveness of perampanel as only concomitant antiseizure medication for highly active epilepsy: insight from a real-world, multicenter retrospective study

Angelo Pascarella  1   2 , Marilisa Pasquale  1   2 , Domenico Abelardo  1   2 , Sara Gasparini  1   2 , Oreste Marsico  1 , Roberta Cutellè  1   2 , Vittoria Cianci  3 , Alfonso Iudice  4 , Francesca Bisulli  5   6 , Paolo Bonanni  7 , Emanuele Caggia  8 , Alfredo D'Aniello  9 , Carlo Di Bonaventura  10 , Jacopo C DiFrancesco  11 , Elisabetta Domina  12 , Fedele Dono  13 , Antonio Gambardella  1   14 , Carla Marini  15 , Alfonso Marrelli  16 , Sara Matricardi  17 , Alessandra Morano  10 , Francesco Paladin  18 , Rosaria Renna  19 , Marta Piccioli  20 , Pasquale Striano  21   22 , Michele Ascoli  23 , Angela La Neve  24 , Emilio Le Piane  25 , Alessandro Orsini  26 , Claudia Torino  27 , Simone Beretta  11 , Umberto Aguglia  1   2 , Edoardo Ferlazzo  28   29 ; PEROC Study Group
Collaborators, Affiliations
Observational Study

Effectiveness of perampanel as only concomitant antiseizure medication for highly active epilepsy: insight from a real-world, multicenter retrospective study

Angelo Pascarella et al. J Neurol. .

Abstract

Introduction: Managing patients with highly frequent seizures poses significant challenges for clinicians due to their high resistance to therapy. This study aims to evaluate the 12-month efficacy, safety, and tolerability of PER as the sole add-on therapy for patients with highly active epilepsy in a real-world setting.

Methods: Data from the previous Italian retrospective, observational, multicenter "PERampanel as Only Concomitant Antiseizure Medication" (PEROC) study were analyzed, categorizing patients by baseline seizure frequency into three groups: < 5, 5-20, and > 20 seizures/month. Retention, responder (≥ 50% seizure reduction) rates, seizure-free rates and adverse events (AEs) were analyzed. Sub-analyses examined early (≤ 1 previous ASM) vs. late (> 2 previous ASMs) add-on groups.

Results: The sample included 485 patients with focal and generalized epilepsy: 354 with < 5 seizures/month, 79 with 5-20, and 52 with > 20 seizures/month. Retention rates at 12 months were 75.1%, 68%, and 58.1.7%, respectively. Perampanel significantly reduced seizure frequency in all groups, with responder rates of 71.2%, 61.8%, and 63.2% at the 12-month follow-up. Patients with more frequent seizures (> 20 and 5-20 seizures/month) had lower seizure-free rates (15.8% and 23.5%) compared to those with < 5 seizures/month (49.5%, p = 0.001). AEs, mainly dizziness and irritability occurred in 30% of patients, without significant differences between groups (p = 0.092).

Conclusions: PER, as the sole adjunctive therapy, demonstrated good effectiveness and tolerability in a real-world setting, even for patients with highly active epilepsy. These findings suggest PER as a valuable early treatment option to improve seizure control and quality of life in this challenging population.

Keywords: Anti-seizure medication; Drug-refractory epilepsy; Early add-on; Real-world evidence; Seizure freedom; Very active epilepsy.

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Conflict of interest statement

Declarations. Conflict of interest: Umberto Aguglia received speaker honoraria from Eisai; Fedele Dono received travel support and speaker honoraria from EISAI; Alfredo D'Aniello received Research grant for UCB Pharma and Speaker/Honoraria for Eisai, UCB Pharma, Angelini Pharma and Lusofarmaco; Giancarlo Di Gennaro received speaker honoraria from EISAI, UCB-Pharma, Livanova, Lusofarmaco, GW Pharmaceuticals. Served on advisory boards for Bial, Arvelle Therapeutics, Angelini Pharma; Edoardo Ferlazzo received speaker honoraria and advisory board from Arvelle Therapeutics, UCB Pharma, Eisai Pharma, Angelini Pharma; Sara Matricardi has served on an advisory board from Eisai outside the submitted work; Alessandra Morano received speaker honoraria from EISAI, UCB-Phrama, Lusofarmaco, Ecupharma, Jazz Pharmaceuticals and Taked, serve on advisory board for Jazz Pharmaceuticals; Marta Piccioli received speaker honoraria from EISAI, UCB Pharma, Angelini Pharma, Jazz Pharmaceuticals, Italfarmaco; Orsini Alessandro received speaker honoraria and advisory boards by Jazz Pharmaceuticals; Pasquale Striano received speaker honoraria and advisory boards for BioMarin, Zogenyx, Poveca, research funding by Jazz Pharmaceuticals, Kolfarma Srl. All other authors have no competing interests to declare that are relevant to the content of this article. Consent to participate: Informed consent was obtained from all participants or their legal representatives. Ethical statement: The study was performed following the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The study protocol was approved by the local Ethics Committee (Comitato Etico Sezione Area Centro Regione Calabria; Prot. N. 126, dated April 16, 2020).

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