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Introduction <p>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.</p> Methods <p>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.</p> Results <p>Among the 850 subjects included in this analysis (259, 240 and 351 receiving LCM, BRV and PER, respectively; 53.4% female; median age 43&#xa0;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.</p> Conclusion <p>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.</p>

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

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  • 发表日期：

    2025年11月20日

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  • Roberta Roberti,
  • Cristina Politi,
  • Francesca Anzellotti,
  • 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,
  • Antonio Gambardella,
  • Alfonso Giordano,
  • Angelo Labate,
  • Angela La Neve,
  • Simona Lattanzi,
  • Ugo Leggio,
  • Claudio Liguori,
  • Marta Maschio,
  • Pietro Mattioli,
  • Annacarmen Nilo,
  • Francesca Felicia Operto,
  • Angelo Pascarella,
  • Giada Pauletto,
  • Luciano Pellegrino,
  • Rosaria Renna,
  • Gionata Strigaro,
  • Vincenzo Andreone,
  • Dario Arnaldi,
  • Valeria Badioni,
  • Chiara Bedetti,
  • Lara Buttarelli,
  • Claudia Cagnetti,
  • Roberto Cantello,
  • Alberto Danieli,
  • Francesco Deleo,
  • Giacomo Evangelista,
  • Mariana Fernandes,
  • Francesco Fortunato,
  • Sara Gasparini,
  • Matilde Lazzari,
  • Andrea Maialetti,
  • Nicola Biagio Mercuri,
  • Miriam Olivieri,
  • Elisa Osanni,
  • Maria Grazia Pascarella,
  • Chiara Pastori,
  • Stefano L Sensi,
  • Payam Tabaee Damavandi,
  • Lorenzo Tinti,
  • Lorenzo Verriello,
  • Flavio Villani,
  • Pio Zoleo,
  • Emilio Russo,
  • Gianfranco Di Gennaro

摘要

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.