Comparative Effectiveness of Brivaracetam, Cenobamate, Lacosamide, and Perampanel in Focal Epilepsy
Year: 2026
Type: article
Abstract: Importance: Treatment decisions in drug-resistant focal epilepsy remain largely empirical, as direct comparative evidence among newer antiseizure medications (ASMs) is limited. Real-world data can complement randomized clinical trials by providing insights into long-term effectiveness and safety across diverse populations. Objective: To compare effectiveness and safety of brivaracetam, cenobamate, lacosamide, and perampanel as adjunctive therapies in adults with drug-resistant focal epilepsy. Design, Setting, and Participants: This was a multicenter pooled analysis of 4 previously conducted retrospective real-world medical record-review studies (January 2017-January 2024). Included were adult patients (aged ≥16 years) with drug-resistant focal epilepsy, as defined by the International League Against Epilepsy. Participants were recruited from 71 epilepsy centers. Exposures: Add-on treatment with brivaracetam, cenobamate, lacosamide, or perampanel. Main Outcomes and Measures: The primary outcome was the responder rate at 6 months, defined as greater than or equal to 50% seizure frequency reduction from baseline. Secondary outcomes included 12-month responder rate, seizure freedom (≥3 months at 6 months and ≥6 months at 12 months), and 12-month ASM retention. Safety was assessed by incidence of adverse effects. Generalized linear mixed models adjusted for demographic and clinical covariates were used to compare treatment outcomes, with cenobamate as reference ASM. Results: Of 2386 ASM prescriptions screened, 1993 prescriptions from 1949 patients (1036 of 1947 female [53.2%]; sex information was missing in 0.1% of prescriptions) with a median (IQR) age of 42 (29-55) years at ASM prescription, met inclusion criteria and were included in the pooled analysis. Brivaracetam accounted for 953 prescriptions (47.8%), followed by perampanel (607 [30.5%]), lacosamide (241 [12.1%]), and cenobamate (192 [9.6%]). After adjustment, cenobamate demonstrated significantly higher odds of 50% or greater response at 6 months compared with brivaracetam (odds ratio [OR], 0.18; 95% CI, 0.12-0.28; P < .001), perampanel (OR, 0.26; 95% CI, 0.16-0.42; P < .001), and lacosamide (OR, 0.29; 95% CI, 0.17-0.49; P < .001). Results were consistent for secondary effectiveness outcomes at 12 months, with cenobamate outperforming other ASMs in terms of 50% or greater response and seizure freedom. Cenobamate was associated with the highest rate of adverse effects during follow-up (111 [57.8%]), and lacosamide was associated with the lowest (35 [14.8%]). Cenobamate was associated with a higher likelihood of treatment retention at 12 months compared with brivaracetam (OR, 0.43; 95% CI, 0.26-0.69; P < .001) and perampanel (OR, 0.56; 95% CI, 0.32-0.99; P = .047), with no significant difference vs lacosamide (OR, 0.81; 95% CI, 0.41-1.59; P = .53). Conclusions and Relevance: These study findings suggest superior effectiveness of cenobamate over brivaracetam, lacosamide, and perampanel in adults with drug-resistant focal epilepsy in a large real-world setting.
Source: JAMA Neurology
Authors: Emanuele Cerulli Irelli, Roberta Roberti, Maria Sole Borioni, Francesca Anzellotti, Vincenzo Belcastro, Simone Beretta, Giovanni Boero, Paolo Bonanni, Valentina Chiesa, Alfredo D’Aniello, Filippo Dainese, Francesco Deleo, Giovanni De Maria, Giancarlo Di Gennaro, Gianfranco Di Gennaro, Giuseppe Didato, Fedele Dono, Giovanni Falcicchio, Edoardo Ferlazzo, Francesco Fortunato, Angela La Neve, Oriano Mecarelli, Elisa Montalenti, Alessandra Morano, Annacarmen Nilo, Francesca Felicia Operto, Francesco Paladin, Angelo Pascarella, Giada Pauletto, Nicola Pietrafusa, Pietro Pignatta, Patrizia Pulitano, Rosaria Renna, Eleonora Rosati, Ilaria Sammarra, Carlo Di Bonaventura, Emilio Russo, Simona Lattanzi, Comparative REal-World Evidence (CREW) Study Group, Domenico Abelardo, Angela Alicino, Vincenzo Andreone, Dario Arnaldi, Giovanni Assenza, Valeria Badioni, Irene Bagnasco, Emanuele Bartolini, Maria A. Bassetti, Giulia Battaglia, Chiara Bedetti, Francesca Bisulli, Francesco Brigo, Emanuele Caggia, Claudia Cagnetti, Costanza Calabrese, Laura Canafoglia, Maria P. Canevini, Sara Casciato, Susanna Casellato, Natascia Casula, Edward Cesnik, Gigliola Chianale, Clotilde Ciampa, Vittoria Cianci, Roberta Ciuffini, Dario Cocito, Francesco Corea, Cinzia Costa, Giovanni Crichiutti, Edoardo Cumbo, Giuseppe D'Orsi, Payam T. Damavandi, Alberto Danieli, Valentina De Giorgis, Luigi Del Gaudio, Roberta Di Giacomo, Alessandra Di Liberto, Jacopo C. DiFrancesco, Elisabetta Domina, Francesco Donato, Vania Durante, Maurizio Elia, Giacomo Evangelista, Elisa Fallica, Martina Fanella, Alessandra Ferrari, Stefania Filipponi, Nicoletta Foschi, Teresa Francavilla, Silvia Franciotta, Renato Frangiosa, Edoardo Fronzoni, Attilio Gagliano, Antonio Gambardella, Massimo Gangitano, Sara Gasparini, Stefano Gazzina, Anna T. Giallonardo, Francesca Gilio, Alfonso Giordano, Filippo S. Giorgi, Ginevra Giovannelli, Loretta Giuliano, Francesco Habetswallner, Shalom Haggiag, Francesca Izzi, Stella Jensen, Angelo Labate, Ugo Leggio, Claudio Liguori, Concetta Luisi, Angelica Lupato, Greta Macorig, Andrea Maialetti, Maria M. Mancardi, Daniela Marino, Alfonso Marrelli, Marta Maschio, Addolorata Mascia, Pietro Mattioli, Sara Matricardi, Adolfo Mazzeo, Alessandra Mazzeo, Stefano Meletti, Miriam Olivieri, Alessandro Orsini, Elisa Osanni, Pasquale Palumbo, Chiara Panzini, Maria Grazia Pascarella, Chiara Pastori, Gabriella Perri, Marianna Pezzella, Federico Piazza, Marta Piccioli, Laura R. Pisani, Chiara Pizzanelli, Patrizia Pollicino, Monica Puligheddu, Giuseppina Pustorino, Stefano Quadri, Pier Paolo Quarato, Federica Ranzato, Emilia Ricci, Adriana Rum, Licia Salimbene, Ersilia Savastano, Stefano L. Sensi, Orazio Spitaleri, David Stokelj, Pasquale Striano, Gionata Strigaro, Elena Tartara, Laura Tassi, Lorenzo Tinti, Mario Tombini, Gemma Tumminelli, Giampaolo Vatti, Lorenzo Verriello, Emanuela Viglietta, Aglaia Vignoli, Flavio Villani, Pio Zoleo, Leila Zummo
Institutions: Sapienza University of Rome, Magna Graecia University, Ospedale SS. Annunziata, Ospedale Maggiore di Lodi, Aziende Socio Sanitarie Territoriale Lodi, University of Milano-Bicocca, IRCCS Eugenio Medea, Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo, Istituto Neurologico Mediterraneo, University of Padua, Azienda Ospedale - Università Padova, Fondazione IRCCS Istituto Neurologico Carlo Besta, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, University of Chieti-Pescara, University of Bari Aldo Moro, Azienda ospedaliera "Bianchi-Melacrino-Morelli", Azienda Ospedaliera Citta' della Salute e della Scienza di Torino, University of Udine, Ospedale Santa Maria della Misericordia di Udine, Bambino Gesù Children's Hospital, Istituti di Ricovero e Cura a Carattere Scientifico, Ospedale Humanitas Gradenigo, Azienda Ospedaliero-Universitaria Careggi, Marche Polytechnic University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7128385034