Peer-reviewedCC BY 4.0Neurological Sciences
Effectiveness and safety of lasmiditan and rimegepant in the acute migraine treatment: an indirect real-world comparison
21 affiliations
- 1Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
- 2Headache Science and Neurorehabilitation Unit, IRCCS Mondino Foundation, Pavia, Italy
- 3Digital and Predictive Medicine, Pharmacology and, Clinical Metabolic Toxicology-Headache Center and Drug Abuse-Laboratory of Clinical Pharmacology and Pharmacogenomics, AOU Policlinico Di Modena, Modena, Italy
- 4Department of Medico-Surgical Sciences and Biotechnologies, Polo, Pontino, Sapienza University of Rome, C.So Della Repubblica 79, 04100 Latina, Italy
- 5Department of Neurosciences “Rita Levi Montalcini”, University of Turin, Turin, Italy
- 6Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
- 7Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy
- 8Department of Health Sciences, University of Florence, Florence, Italy
- 9Headache Center, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania ‘Luigi Vanvitelli’, Naples, Italy
- 10Headache Center of Clinical Neurology of Istituto Clinico Città Di Brescia, Brescia, Italy
- 11Neuroalgology Unit and Headache Center, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
- 12L. Amaducci” Neurological Clinic, University of Bari, Bari, Italy
- 13IRCCS Istituto Delle Scienze Neurologiche Di Bologna, UOC Clinica Neurologica Metropolitana - Programma Cefalee Ed Algie Facciali, Bologna, Italy
- 14Neurology Unit, Ospedale Santo Stefano, USL Toscana Centro, Prato, Italy
- 15Headache Centre, Neurology - Euganea, Health Unit, Padua, Italy
- 16Clinical Neurology Azienda Sanitaria Friuli Centrale. Department of Medicine, University of Udine, Udine, Italy
- 17Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy
- 18Headache Centre, Clinical Unit of Neurology, School of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services, ASUGI, University of Trieste, Trieste, Italy
- 19Unit of Neurology, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- 20Department of Neurosciences, AOU Renato Dulbecco, Catanzaro, Italy
- 21Department of Neurology- Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy
Abstract
Aim: Rimegepant and lasmiditan are effective acute migraine treatments, but real-world head-to-head comparative data are lacking. We aimed to compare their effectiveness and tolerability in clinical practice.
Methods: This post-hoc study indirectly compared two prospective, multicenter, real-world studies (GAINER and DART). Participants treated up to four migraine attacks with rimegepant 75 mg orally disintegrating tablets or lasmiditan 50 or 100 mg. Data were collected using an electronic diary every 30 min up to 2 hours after dosing. The co-primary outcomes were 2-hour pain freedom and incidence of adverse events (AEs) comparing rimegepant with lasmiditan in the first treated attack.
Results: The overall cohort included 249 individuals, 58 treated with lasmiditan and 191 with rimegepant (81.1% females, age 45.8 [43.4–48.1] years, 9.6 [8.3 – 10.8] monthly migraine days, 26.9% with chronic migraine). Pain freedom 2-hour post dose in the first treated attack was comparable between rimegepant and lasmiditan (43.5%, n = 83 vs. 32.8%, n = 19, p = 0.171). The relative risk (RR) of achieving 2-hour pain freedom with lasmiditan versus rimegepant was 0.75 [0.50 – 1.28] (p = 0.169). The percentage of participants who reported at least one AE in the first treated attack was higher with lasmiditan than with rimegepant (53.4% vs. 11.5%; RR 4.64 [2.93–7.35], p < 0.001).
Conclusion: Lasmiditan and rimegepant demonstrated comparable effectiveness, although more participants reported AEs after lasmiditan intake. Nonetheless, this indirect comparison warrants further confirmation.
Trial registration: GAINER registration at www.clinicaltrial.gov: NCT05903027; DART registration at www.clinicaltrial.gov: NCT05903040.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s10072-026-09510-6.
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BibTeX
@article{vaghi2026effectiveness,
title = {{Effectiveness and safety of lasmiditan and rimegepant in the acute migraine treatment: an indirect real-world comparison}},
author = {Gloria Vaghi and Luigi Francesco Iannone and Gabriele Sebastianelli and Elisa Maria Piella and Michele Corrado and Marina Romozzi and Federico De Santis and Raffaele Ornello and Francesca Pistoia and Francesco De Cesaris and Andrea Burgalassi and Gianluca Coppola and Marcello Silvestro and Innocenzo Rainero and Giorgio Dalla Volta and Danilo Antonio Montisano and Simona Guerzoni and Maria Pia Prudenzano and Davide Mascarella and Gianluca Avino and Edoardo Mampreso and Mariarosaria Valente and Stefania Battistini and Antonio Granato and Maria Albanese and Michele Trimboli and Alberto Doretti and Roberto De Icco and Cristina Tassorelli and Cristina Tassorelli and Martina Giraudo and Francesco Casillo and Flavia Lo Castro and Rossana Allamprese and Alessia Agostinelli and Gennaro Saporito and Simona Sacco and Antonio Munafò and Alberto Chiarugi and Giovanna Carlucci and Antonio Russo and Marco Bolchini and Matteo Cortinovis and Licia Grazzi and Martino Gentile and Adriana Fallacara and Sabina Cevoli and Enrico Grassi and Catello Vollono and Sara Pez and Luca Bartole and Antonio Meo and Vittoria Carla D’Agostino and Nicola Mercuri Biagio and Eleonora Colombo and Alessandro Cocuzza},
journal = {Neurological Sciences},
year = {2026},
month = nov,
doi = {10.1007/s10072-026-09510-6},
url = {https://doi.org/10.1007/s10072-026-09510-6},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Effectiveness and safety of lasmiditan and rimegepant in the acute migraine treatment: an indirect real-world comparison
AU - Gloria Vaghi
AU - Luigi Francesco Iannone
AU - Gabriele Sebastianelli
AU - Elisa Maria Piella
AU - Michele Corrado
AU - Marina Romozzi
AU - Federico De Santis
AU - Raffaele Ornello
AU - Francesca Pistoia
AU - Francesco De Cesaris
AU - Andrea Burgalassi
AU - Gianluca Coppola
AU - Marcello Silvestro
AU - Innocenzo Rainero
AU - Giorgio Dalla Volta
AU - Danilo Antonio Montisano
AU - Simona Guerzoni
AU - Maria Pia Prudenzano
AU - Davide Mascarella
AU - Gianluca Avino
AU - Edoardo Mampreso
AU - Mariarosaria Valente
AU - Stefania Battistini
AU - Antonio Granato
AU - Maria Albanese
AU - Michele Trimboli
AU - Alberto Doretti
AU - Roberto De Icco
AU - Cristina Tassorelli
AU - Cristina Tassorelli
AU - Martina Giraudo
AU - Francesco Casillo
AU - Flavia Lo Castro
AU - Rossana Allamprese
AU - Alessia Agostinelli
AU - Gennaro Saporito
AU - Simona Sacco
AU - Antonio Munafò
AU - Alberto Chiarugi
AU - Giovanna Carlucci
AU - Antonio Russo
AU - Marco Bolchini
AU - Matteo Cortinovis
AU - Licia Grazzi
AU - Martino Gentile
AU - Adriana Fallacara
AU - Sabina Cevoli
AU - Enrico Grassi
AU - Catello Vollono
AU - Sara Pez
AU - Luca Bartole
AU - Antonio Meo
AU - Vittoria Carla D’Agostino
AU - Nicola Mercuri Biagio
AU - Eleonora Colombo
AU - Alessandro Cocuzza
PY - 2026
DA - 2026/11/05
JO - Neurological Sciences
DO - 10.1007/s10072-026-09510-6
UR - https://doi.org/10.1007/s10072-026-09510-6
AB - Aim: Rimegepant and lasmiditan are effective acute migraine treatments, but real-world head-to-head comparative data are lacking. We aimed to compare their effectiveness and tolerability in clinical practice. Methods: This post-hoc study indirectly compared two prospective, multicenter, real-world studies (GAINER and DART). Participants treated up to four migraine attacks with rimegepant 75 mg orally disintegrating tablets or lasmiditan 50 or 100 mg. Data were collected using an electronic diary every 30 min up to 2 hours after dosing. The co-primary outcomes were 2-hour pain freedom and incidence of adverse events (AEs) comparing rimegepant with lasmiditan in the first treated attack. Results: The overall cohort included 249 individuals, 58 treated with lasmiditan and 191 with rimegepant (81.1% females, age 45.8 [43.4–48.1] years, 9.6 [8.3 – 10.8] monthly migraine days, 26.9% with chronic migraine). Pain freedom 2-hour post dose in the first treated attack was comparable between rimegepant and lasmiditan (43.5%, n = 83 vs. 32.8%, n = 19, p = 0.171). The relative risk (RR) of achieving 2-hour pain freedom with lasmiditan versus rimegepant was 0.75 [0.50 – 1.28] (p = 0.169). The percentage of participants who reported at least one AE in the first treated attack was higher with lasmiditan than with rimegepant (53.4% vs. 11.5%; RR 4.64 [2.93–7.35], p < 0.001). Conclusion: Lasmiditan and rimegepant demonstrated comparable effectiveness, although more participants reported AEs after lasmiditan intake. Nonetheless, this indirect comparison warrants further confirmation. Trial registration: GAINER registration at www.clinicaltrial.gov: NCT05903027; DART registration at www.clinicaltrial.gov: NCT05903040. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s10072-026-09510-6.
SN - 1590-1874
SN - 1590-3478
ER -