A real-world comparison among third-generation antiseizure medications: Results from the COMPARE study

Roberta Roberti; Gianfranco Di Gennaro; Francesca Anzellotti; Dario Arnaldi; Vincenzo Belcastro; Simone Beretta; Giovanni Boero; Paolo Bonanni; Laura Canafoglia; Alfredo D'Aniello; Filippo Dainese; Carmen De Caro; Giancarlo Di Gennaro; Roberta Di Giacomo; Jacopo C DiFrancesco; Fedele Dono; Giovanni Falcicchio; Edoardo Ferlazzo; Nicoletta Foschi; Silvia Franciotta; Antonio Gambardella; Alfonso Giordano; Luigi Francesco Iannone; Angelo Labate; Angela La Neve; Simona Lattanzi; Ugo Leggio; Claudio Liguori; Marta Maschio; Annacarmen Nilo; Francesca Felicia Operto; Angelo Pascarella; Giada Pauletto; Rosaria Renna; Gionata Strigaro; COMPARE Study Group; Emilio Russo

doi:10.1111/epi.17843

A real-world comparison among third-generation antiseizure medications: Results from the COMPARE study

Epilepsia. 2024 Feb;65(2):456-472. doi: 10.1111/epi.17843. Epub 2023 Dec 16.

Authors

Roberta Roberti¹, Gianfranco Di Gennaro¹, Francesca Anzellotti², Dario Arnaldi^{3

4}, Vincenzo Belcastro⁵, Simone Beretta⁶, Giovanni Boero⁷, Paolo Bonanni⁸, Laura Canafoglia⁹, Alfredo D'Aniello¹⁰, Filippo Dainese¹¹, Carmen De Caro¹, Giancarlo Di Gennaro¹⁰, Roberta Di Giacomo¹², Jacopo C DiFrancesco⁶, Fedele Dono^{2

13}, Giovanni Falcicchio¹⁴, Edoardo Ferlazzo^{15

16}, Nicoletta Foschi¹⁷, Silvia Franciotta¹¹, Antonio Gambardella¹⁸, Alfonso Giordano¹⁹, Luigi Francesco Iannone²⁰, Angelo Labate²¹, Angela La Neve¹⁴, Simona Lattanzi¹⁷, Ugo Leggio²², Claudio Liguori^{23

24}, Marta Maschio²⁵, Annacarmen Nilo²⁶, Francesca Felicia Operto²⁷, Angelo Pascarella^{15

16}, Giada Pauletto²⁸, Rosaria Renna²⁹, Gionata Strigaro^{30

31}; COMPARE Study Group; Emilio Russo¹

Affiliations

¹ Science of Health Department, School of Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy.
² Department of Neurology, Epilepsy Center, SS Annunziata Hospital, Chieti, Italy.
³ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Clinical Neurology, University of Genoa, Genoa, Italy.
⁴ IRCSS Ospedale Policlinico San Martino, Genoa, Italy.
⁵ Neurology Unit, Maggiore Hospital, ASST Lodi, Lodi, Italy.
⁶ Department of Neurology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
⁷ Complex Structure of Neurology, SS Annunziata Hospital, Taranto, Italy.
⁸ Epilepsy and Clinical Neurophysiology Unit, Scientific Institute, IRCCS Eugenio Medea, Conegliano, Treviso, Italy.
⁹ Integrated Diagnostics for Epilepsy, Fondazione IRCCS Istituto Neurologico Besta, Milan, Italy.
¹⁰ IRCCS Neuromed, Pozzilli, Italy.
¹¹ Clinical Neurophysiology Unit, Clinical Neurology, DIDAS Department, Padua, Italy.
¹² Epilepsy Unit, Fondazione IRCCS Istituto Neurologico Besta, Milan, Italy.
¹³ Department of Neuroscience, Imaging and Clinical Science, D'Annunzio University of Chieti-Pescara, Chieti, Italy.
¹⁴ DiBraiN Department, University of Bari Aldo Moro, Bari, Italy.
¹⁵ Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy.
¹⁶ Regional Epilepsy Center, Bianchi-Melacrino-Morelli Great Metropolitan Hospital, Reggio Calabria, Italy.
¹⁷ Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy.
¹⁸ Department of Medical and Surgical Sciences, Institute of Neurology, Magna Graecia University of Catanzaro, Catanzaro, Italy.
¹⁹ Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy.
²⁰ Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy.
²¹ Neurophysiopathology and Movement Disorders Clinic, University of Messina, Messina, Italy.
²² Unit of Neurophysiopathology, ASST Spedali Civili, Brescia, Italy.
²³ Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
²⁴ Neurology Unit, Epilepsy Center, University Hospital Tor Vergata, Rome, Italy.
²⁵ Center for Tumor-Related Epilepsy, UOSD Neuro-Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
²⁶ Clinical Neurology Unit, Department of Head, Neck, and Neurosciences, Santa Maria della Misericordia University Hospital, Udine, Italy.
²⁷ Child and Adolescent Neuropsychiatry Unit, Department of Medicine, Surgery, and Dentistry, University of Salerno, Fisciano, Italy.
²⁸ Neurology Unit, Department of Head, Neck, and Neurosciences, Santa Maria della Misericordia University Hospital, Udine, Italy.
²⁹ Neurology and Stroke Unit, Department of Emergency and Acceptance, AORN Antonio Cardarelli Hospital, Naples, Italy.
³⁰ Neurology Unit, Department of Translational Medicine, Epilepsy Center, University of Piemonte Orientale, Novara, Italy.
³¹ Maggiore della Carità University Hospital, Novara, Italy.

PMID: 38052481
DOI: 10.1111/epi.17843

Abstract

Objective: There are few comparative data on the third-generation antiseizure medications (ASMs). We aimed to assess and compare the effectiveness of brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) in people with epilepsy (PWE). Efficacy and tolerability were compared as secondary objectives.

Methods: This multicenter, retrospective study collected data from 22 Italian neurology/epilepsy centers. All adult PWE who started add-on treatment with one of the studied ASMs between January 2018 and October 2021 were included. Retention rate was established as effectiveness measure and described using Kaplan-Meier curves and the best fitting survival model. The responder status and the occurrence of adverse events (AEs) were used to evaluate efficacy and safety, respectively. The odds of AEs and drug efficacy were estimated by two multilevel logistic models.

Results: A total of 960 patients (52.92% females, median age = 43 years) met the inclusion criteria. They mainly suffered from structural epilepsy (52.29%) with monthly (46.2%) focal seizures (69.58%). Compared with LCM, all the studied ASMs had a higher dropout risk, statistically significant in the BRV levetiracetam (LEV)-naïve (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.17-3.29) and PER groups (HR = 1.64, 95% CI = 1.06-2.55). Women were at higher risk of discontinuing ESL (HR = 5.33, 95% CI = 1.71-16.61), as well as PER-treated patients with unknown epilepsy etiology versus those with structural etiology (HR = 1.74, 95% CI = 1.05-2.88). BRV with prior LEV therapy showed lower odds of efficacy (odds ratio [OR] = .08, 95% CI = .01-.48) versus LCM, whereas a higher efficacy was observed in women treated with BRV and LEV-naïve (OR = 10.32, 95% CI = 1.55-68.78) versus men. PER (OR = 6.93, 95% CI = 3.32-14.44) and BRV in LEV-naïve patients (OR = 6.80, 95% CI = 2.64-17.52) had a higher chance of AEs than LCM.

Significance: Comparative evidence from real-world studies may help clinicians to tailor treatments according to patients' demographic and clinical characteristics.

Keywords: brivaracetam; comparative study; eslicarbazepine acetate; lacosamide; perampanel.

Publication types

Multicenter Study

MeSH terms

Adult
Anticonvulsants / adverse effects
Epilepsies, Partial* / drug therapy
Epilepsy* / drug therapy
Female
Humans
Lacosamide / therapeutic use
Levetiracetam / therapeutic use
Male
Nitriles*
Pyridones*
Pyrrolidinones / therapeutic use
Retrospective Studies
Treatment Outcome

Substances

Anticonvulsants
Levetiracetam
Lacosamide
Pyrrolidinones
perampanel
Nitriles
Pyridones