doi:10.1186/s10194-025-02239-1engMuñoz-Vendrell, AlbertCampoy-Díaz, SergioValín-Villanueva, PalomaCasas-Limón, JavierFernández-Lázaro, IrisGonzález-García, NuriaSantos-Lasaosa, SoniaGonzález Osorio, YésicaGonzalez-Martinez, AliciaCampdelacreu, JaumePortocarrero-Sánchez, LeonardoCano Sánchez, Luis MiguelGarcía Sánchez, Sonia MaríaPérez-de-la-parte, AlbaMorollón Sánchez-Mateos, NoemíLópez-Bravo, AlbaMínguez-Olaondo, AneSánchez-Soblechero, AntonioLozano Ros, AlbertoMorales Hernández, CristianAndrés López, AlbertoLayos-Romero, AlmudenaCaronna, EdoardoTorres-Ferrús, MartaAlpuente, AliciaPozo-Rosich, PatriciaBelvís, RobertGarcia-Azorin, DavidDíaz-de-Terán, JavierGuerrero-Peral, Ángel LuisGago-Veiga, Ana BeatrizHuerta-Villanueva, MarianoAtogepant after anti-CGRP monoclonal antibodies failure in migraine: a multicenter real-world study of effectiveness, safety, persistence and predictors of responseART-2025-147440Background Atogepant is approved for migraine prevention and has shown strong efficacy in clinical trials. However, its effectiveness following failure of anti-CGRP monoclonal antibodies (MAbs) has not been evaluated in large real-world populations. Methods This multicenter observational study conducted across Spanish headache units included adults with migraine who initiated atogepant after failure of ≥1 anti-CGRP MAb and had≥3 months of follow-up. Baseline demographic and clinical variables were collected prospectively, with follow-up assessments at months 3 and 6. The primary outcome was the proportion of patients achieving a≥50% reduction in monthly migraine days (MMD) at three months. Secondary outcomes included≥30%, ≥75%, and 100% response rates; changes in headache days, pain intensity, acute medication use, and patient-reported outcomes; adverse events; treatment persistence; and factors associated with response. Results A total of 252 patients were included (mean age 48.9±12 years; 83.3% female; 80.6% with chronic migraine; 45.6% with continuous daily headache). Prior to atogepant, 39.7% had failed one anti-CGRP MAb, 27.0% two, 20.2% three, and 13.1% four. Median baseline MMD was 16, monthly headache days 27, and acute medication days 20. At 3 months, 44.4% achieved a≥30% reduction in MMD, 29.7% ≥50%, and 11.7% ≥75%. Adverse events were reported in 52.5% of patients, most commonly constipation (30%) and nausea (25%). At three months, 26.2% had discontinued treatment (65.1% due to inefficacy, 28.8% due to intolerance). Treatment persistence at 180 days was 61% (95% CI 54 to 69%). A higher number of previously failed MAbs was independently associated with reduced odds of ≥50% response (RR 0.79, 95% CI 0.64 to 0.97). Moreover, a higher number of previously failed MAbs was associated with diminished improvements across multiple clinical endpoints, including headache frequency, intensity, acute medication use, and disability measures. Conclusion Atogepant may represent a viable treatment option for patients with migraine who have failed antiCGRP MAbs. In this large real-world cohort, approximately one-third of patients achieved a≥50% response, despite a treatment-refractory profile. However, the likelihood of response decreases with a higher number of previously failed MAbs, and mild adverse events are frequent.2025http://zaguan.unizar.es/record/16594510.1186/s10194-025-02239-1http://zaguan.unizar.es/record/165945oai:zaguan.unizar.es:165945The Journal of headache and pain 27, 2 (2025), [12 pp.]byhttps://creativecommons.org/licenses/by/4.0/deed.esinfo:eu-repo/semantics/openAccess