doi:10.1177/03331024261431337engGago-Veiga, Ana BeatrizLópez-Rodríguez, Ana BelénSánchez Jiménez, MarinaIglesias Rubio, ÁlvaroMontes, NuriaCamiña Muñiz, JavierDomínguez Gallego, MartaCalle de Miguel, CarlosLatorre, GermánRodríguez-Vico, JaimeJaimes, AlexGómez García, AndreaUrtiaga, SaraGonzález Salaices, MartaDileone, MicheleGonzález-García, NuriaPorta-Etessam, JesúsCuadrado, María-LuzHerrero San-Martín, AlejandroGuerrero-Peral, Ángel-LuisGonzález-Osorio, YesicaCasas-Limón, JavierSánchez-Soblechero, AntonioLozano-Ros, AlbertoDíaz-De-Terán, JavierPortocarrero-Sánchez, LeonardoMolina-Martínez, Francisco-JoséSantos-Lasaosa, SoniaMartín-Ávila, GuillermoRiva, ElenaFernández-Lázaro, IrisAtogepant for migraine in real-world clinical practice: Insights from a large multicentre study in a treatment-resistant population (GEMA project)ART-2026-148964Aim Atogepant is a novel oral calcitonin gene-related peptide (CGRP) receptor antagonist approved for migraine prevention. This study primarily evaluated its effectiveness and safety in real-world clinical practice, focusing on patients with treatment-resistant migraine, defined according to the European Headache Federation (EHF) criteria as failure of at least three classes of preventive medications, including onabotulinumtoxinA or anti-CGRP monoclonal antibodies (mAbs). Methods This prospective multicentre study was conducted across 15 tertiary Headache Units in Spain. Demographic and clinical data, prior preventives, monthly headache days (MHD), monthly migraine days (MMD), and adverse events (AEs) were systematically collected at baseline, 3 months (primary endpoint), and/or 6 months (secondary endpoint). Results AimA total of 513 patients were enrolled (mean age 48 years; 88% women). The 3-month analysis included 455 patients, with median MHD decreasing from 21 (IQR 15-30) to 14 (IQR 6-30) and MMD from 14 (IQR 10-20) to 8 (IQR 3-15) (both p < 0.0001). A ≥ 50% reduction was achieved by 34% (MHD) and 29% (MMD), with ≥75% responses in 16% and 13%. Adverse events were mostly mild, mainly constipation (30%) and nausea (18%), and the 3-month discontinuation rate was 11.8%. Responders had shorter migraine chronicity, less analgesic overuse, and fewer prior preventive failures. Although prior inadequate response to anti-CGRP mAbs reduced the likelihood of improvement, it did not prevent meaningful benefit. At analysis, 151 patients had reached the 6-month visit, showing further improvement (MHD 10 [IQR 5-20]; MMD 6 [IQR 4-12]) and fewer adverse events. Conclusions Atogepant showed robust real-world effectiveness and good tolerability in a large, treatment-resistant migraine cohort, with clinically meaningful improvement at 3 months and incremental benefit in the subgroup evaluated at 6 months. Lower migraine chronicity and fewer prior preventive failures were associated with better outcomes, supporting the earlier introduction of anti-CGRP therapies in clinical practice.2026http://zaguan.unizar.es/record/17047310.1177/03331024261431337http://zaguan.unizar.es/record/170473oai:zaguan.unizar.es:170473info:eu-repo/grantAgreement/ES/ISCIII/i-PFIS-IFI15-00158CEPHALALGIA 46, 4 (2026), 1-15by-nchttps://creativecommons.org/licenses/by-nc/4.0/deed.esinfo:eu-repo/semantics/openAccess