PO-28 | Sex differences in the response to rimegepant for the treatment of acute migraine attacks – insights from the multicenter GAINER study

Raffaele Ornello,¹ Gloria Vaghi,^2,3 Gabriele Sebastianelli,⁴ Francesco Casillo,⁴ Antonio Russo,⁵ Marcello Silvestro,⁵ Francesca Pistoia,¹ Giorgio Dalla Volta,⁶ Matteo Cortinovis,⁶ Alberto Chiarugi,⁷ Danilo Antonio Montisano,⁸ Licia Grazzi,⁸ Maria Pia Prudenzano,⁹ Sabina Cevoli,¹⁰ Edoardo Mampreso,¹¹ Gianluca Avino,¹² Marina Romozzi,¹³ Mariarosaria Valente,¹⁴ Carla Fasano,¹⁵ Stefania Battistini,¹⁶ Antonio Granato,¹⁷ Elisa Maria Piella,¹⁸ Innocenzo Rainero,¹⁸ Federico De Santis,¹ Simona Sacco,¹ Maria Albanese,¹⁹ Michele Trimboli,²⁰ Alberto Doretti,²¹ Cristina Tassorelli,^2,3 Luigi Francesco Iannone,²² Roberto De Icco^2,3 on behalf of the Italian Headache Registry (RICe) Study Group | ¹Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila; ²Department of Brain and Behavioral Sciences, University of Pavia; ³Headache Science and Neurorehabilitation Unit, IRCCS Mondino Foundation, Pavia; ⁴Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, Latina; ⁵Headache Centre, Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples; ⁶Headache Center of Clinical Neurology of Istituto Clinico "Città di Brescia", Brescia; ⁷Department of Health Sciences, University of Florence; ⁸Neuroalgology Unit and Headache Center, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; ⁹Headache Center, Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari; ¹⁰IRCCS Istituto Di Scienze Neurologiche di Bologna, Programma Cefalee e Algie Facciali, Bologna; ¹¹Headache Centre, Neurology - Euganea, Health Unit, Padua; ¹²Neurology Unit, Ospedale Santo Stefano, USL Toscana Centro, Prato; ¹³Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome; ¹⁴Clinical Neurology, Azienda Sanitaria Universitaria Friuli Centrale, Presidio Ospedaliero Santa Maria della Misericordia, Udine; ¹⁵Headache and Facial Pain Center Neurology, AOU Careggi, Florence; ¹⁶Department of Medical, Surgical and Neurological Sciences, University of Siena; ¹⁷Headache Centre, Clinical Unit of Neurology, School of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, ASUGI, University of Trieste; ¹⁸Department of Neurosciences “Rita Levi Montalcini”, University of Turin; ¹⁹Department of Systems Medicine, University of Rome Tor Vergata, Rome; ²⁰University Magna Graecia, Catanzaro; ²¹Department of Neuroscience - Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan; ²²University of Modena and Reggio Emilia, Modena, Italy

Background: Calcitonin gene-related peptide receptor (CGRPr) has a different distribution in the brain of male and female subjects; however, it is unclear whether this affects the response to CGRPr inhibitors. Clinical trial data suggest a decreased efficacy of CGRPr oral inhibitors – i.e., gepants – in males compared with females; however, it is not clear whether this applies to real-world settings. We aimed to test the real-world effectiveness of rimegepant, a CGRPr oral inhibitor, for the acute treatment of migraine in females and males.

Methods: We included patients with either episodic or chronic migraine who treated at least one episode of migraine with rimegepant according to clinicians’ indications from June 2023 to April 2025. We only considered the first attack treated by patients. Our primary outcome was the proportion of pain-free patients two hours after rimegepant intake. Secondary outcomes included pain freedom at 30, 60, and 90 minutes after rimegepant intake and Patient Global Impression of Change (PGIC) scores. Results were compared between females and males via chi-square test.

Results: We included 191 patients of whom 153 (80.1%) were females. The characteristics of males and females were not different except from a lower prevalence of medication overuse in females compared with males (29 [19.0%] vs 13 [34.2%]; p=0.042). More females than males were pain-free at two hours (73 [47.7%] vs 10 [16.3%]; p=0.028). The difference in pain freedom was also significant at 90 minutes (54 [37.8%] vs 5 [14.7%]; p=0.014), while it was not significant at 30 and 60 minutes. Median PGIC score was higher in females than in males (5 [IQR 3-6] vs 3 [IQR 2-5]; p<0.001).

Conclusion: We found a higher effectiveness of rimegepant for the acute treatment of migraine in females compared with males. Nevertheless, the drug was effective in both sexes. Preclinical and clinical studies are needed to elucidate the possible mechanisms determining a sex difference in response to rimegepant.