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. 2025 Nov 20.
doi: 10.1007/s40120-025-00860-5. Online ahead of print.

Lacosamide is Associated with a Higher Treatment Persistence at 12 Months than Brivaracetam and Perampanel Despite Similar Efficacy

Roberta Roberti  1 , Cristina Politi  1   2 , Francesca Anzellotti  3 , Vincenzo Belcastro  4 , Simone Beretta  5 , Giovanni Boero  6 , Paolo Bonanni  7 , Laura Canafoglia  8 , Alfredo D'Aniello  9 , Filippo Dainese  10 , Carmen De Caro  1   11 , Giancarlo Di Gennaro  9 , Roberta Di Giacomo  12 , Jacopo C DiFrancesco  5 , Fedele Dono  3   13 , Giovanni Falcicchio  14 , Edoardo Ferlazzo  15   16 , Nicoletta Foschi  17 , Antonio Gambardella  18 , Alfonso Giordano  19 , Angelo Labate  20 , Angela La Neve  14 , Simona Lattanzi  17 , Ugo Leggio  21 , Claudio Liguori  22   23 , Marta Maschio  24 , Pietro Mattioli  25   26 , Annacarmen Nilo  27 , Francesca Felicia Operto  1   18 , Angelo Pascarella  15   16 , Giada Pauletto  28 , Luciano Pellegrino  10 , Rosaria Renna  29 , Gionata Strigaro  30 ; COMPARE Study Group; Emilio Russo  31 , Gianfranco Di Gennaro  1
Collaborators, Affiliations

Lacosamide is Associated with a Higher Treatment Persistence at 12 Months than Brivaracetam and Perampanel Despite Similar Efficacy

Roberta Roberti et al. Neurol Ther. .

Abstract

Introduction: Evidence directly comparing newer antiseizure medications (ASMs) is limited but crucial for guiding treatment decisions. This study compared the real-world effectiveness and tolerability of brivaracetam (BRV), lacosamide (LCM) and perampanel (PER) as add-on therapy in adults with epilepsy, applying a causal-inference extension of the COMPARE study. The aim of this approach was to overcome the limitations of standard multivariable analyses, better approximate causal effects, and reinforce the credibility of the results.

Methods: Data were retrospectively collected in the Italian multicentre COMPARE study. To emulate a randomized setting, we estimated multinomial propensity scores and applied stabilized inverse probability weights. The primary analysis used a log-logistic accelerated failure time model to estimate time-to-treatment discontinuation, adjusting for adverse events (AEs), clinical response and follow-up duration. Secondary analyses evaluated changes in total and concomitant drug load and tolerability over time.

Results: Among the 850 subjects included in this analysis (259, 240 and 351 receiving LCM, BRV and PER, respectively; 53.4% female; median age 43 years), the estimated probability of 12-month retention was highest for LCM (86.1%), followed by BRV (79.1%) and PER (75.4%). Long-term trends suggested convergence of PER and LCM retention, whereas BRV discontinuation remained higher. In the adjusted analyses, BRV and PER were associated with shorter time-to-treatment discontinuation than LCM, but this negative effect decreased over time, while the beneficial effect of clinical response strengthened. Total drug load increased across all groups but remained lowest for LCM; concomitant ASM load decreased, particularly among responders. AEs were mostly mild, with dizziness, irritability and somnolence the most common AEs. AE rates were initially higher for PER and BRV, but differences diminished over time.

Conclusion: Treatment discontinuation in epilepsy emerges as a dynamic process shaped by both tolerability and clinical response. Early persistence was higher for LCM, whereas long-term retention was improved for BRV and PER. These results support a personalized approach to ASM selection that integrates early tolerability with sustained effectiveness.

Keywords: Antiseizure medications; Comparative analysis; Drug load; Epilepsy; Real world study; Retention rate; Safety.

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Conflict of interest statement

Declarations. Conflict of Interest: Roberta Roberti has received speaker’s or consultancy fees from Eisai, UCB Pharma and Jazz Pharmaceuticals. Francesca Anzellotti has received travel support from Eisai, UCB and Angelini Pharma; and has speaker honoraria from Eisai and Angelini Pharma. Giovanni Boero has received speaker’s or consultancy fees from Eisai, Angelini Pharma and UCB Pharma. Paolo Bonanni has received speaker’s or consultancy fees from Bial, Eisai, GW, LivaNova, Lusofarmaco, Proveca and Roche. Laura Canafoglia has participated in pharmaceutical industry-sponsored clinical trials for UCB Pharma and other pharmaceutical industries; and has received speaker honoraria from Eisai. Alfredo D’Aniello has participated in pharmaceutical industry-sponsored clinical trials for UCB Pharma; has received speaker honoraria and consultancy fees from Eisai, UCB Pharma, Angelini Pharma and Neuraxpharm; and has served on advisory boards for Angelini Pharma. Filippo Dainese has received speaker’s or consultancy fees from UCB Pharma, Eisai and Bial. Giancarlo Di Gennaro has received speaker honoraria from UCB Pharma, Eisai, Lusofarmaco, Livanova, Angelini Pharma and Jazz Pharmaceuticals; and has served on advisory board for Bial, Arvelle, Angelini Pharma, Livanova, Neuraxpharma and UCB Pharma. Fedele Dono has received travel support from Eisai, UCB Pharma and Angelini Pharma; and has received speaker honoraria from Eisai. Giovanni Falcicchio has received speaker fees from Angelini Pharma. Edoardo Ferlazzo has received speaker honoraria from UCB Pharma, Eisai and Angelini Pharma. Antonio Gambardella has received speaker honoraria from UCB Pharma, Eisai, Angelini Pharma, Jazz, Bial and Zambon. Angela La Neve has received speaker’s or consultancy fees from Eisai, Mylan, Sanofi, Bial, GW, Arvelle, Angelini Pharma and UCB Pharma; and has served on scientific advisory boards for GW Pharma, Jazz Pharmaceuticals and Angelini Pharma. Simona Lattanzi has received speaker’s or consultancy fees from Angelini Pharma, Eisai, GW Pharmaceuticals, Medscape and UCB Pharma; and has served on advisory boards for Angelini Pharma, Arvelle Therapeutics, BIAL, Eisai and GW Pharmaceuticals outside the submitted work. Simona Lattanzi received research grant support from the Ministry of Health and the Ministry of University and Research outside the submitted work. Pietro Mattioli has received speaker honoraria from Angelini Pharma. Emilio Russo has received speaker fees or funding from and has participated on advisory boards for Angelini Pharma, Eisai, Ethypharm, GW Pharmaceuticals, Jazz Pharmaceuticals, Kolfarma and UCB Pharma. Simona Lattanzi is an Editorial Board member of Neurology and Therapy, but was not involved in the selection of peer reviewers for the manuscript or in any of the subsequent editorial decisions. Cristina Politi, Vincenzo Belcastro, Simone Beretta, Carmen De Caro, Roberta Di Giacomo, Jacopo C DiFrancesco, Nicoletta Foschi, Alfonso Giordano, Angelo Labate, Ugo Leggio, Claudio Liguori, Marta Maschio, Annacarmen Nilo, Francesca Felicia Operto, Angelo Pascarella, Giada Pauletto, Luciano Pellegrino, Rosaria Renna and Gionata Strigaro and Gianfranco Di Gennaro have no conflicts of interest. Ethical Approval: The overall, anonymized data collection was approved by the Ethics Committee of Calabria Region, Italy (protocol number 115/19) and conducted in accordance with the Declaration of Helsinki. As the study was based on retrospective and fully anonymized data, written informed consent was not required.

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