GIANT: a prospective, multicenter, real-world study on the effectiveness, safety, and tolerability of atogepant in migraine patients with multiple therapeutic failures
Abstract Background Atogepant, the first oral CGRP receptor antagonist approved for migraine prevention, has demonstrated efficacy and safety in randomized clinical trials (RCT). However, prospective real-world data are lacking. Objective To explore the effectiveness, safety, and tolerability of ato...
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2025-05-01
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| Series: | The Journal of Headache and Pain |
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| Online Access: | https://doi.org/10.1186/s10194-025-02068-2 |
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| author | Piero Barbanti Gabriella Egeo Francesca Pistoia Cinzia Aurilia Paola Scatena Steno Rinalduzzi Silvia Strumia Antonio Salerno Fabio Frediani Andrea Galli Massimo Autunno Laura Di Clemente Maurizio Zucco Maria Albanese Francesco Bono Pietrantonio Bruno Laura Borrello Stefano Messina Alberto Doretti Angelo Ranieri Cecilia Camarda Rosario Vecchio Valeria Drago Giulia Fiorentini Carlo Tomino Stefano Bonassi Paola Torelli Alice Mannocci for the Italian Migraine Registry (I-GRAINE) study group |
| author_facet | Piero Barbanti Gabriella Egeo Francesca Pistoia Cinzia Aurilia Paola Scatena Steno Rinalduzzi Silvia Strumia Antonio Salerno Fabio Frediani Andrea Galli Massimo Autunno Laura Di Clemente Maurizio Zucco Maria Albanese Francesco Bono Pietrantonio Bruno Laura Borrello Stefano Messina Alberto Doretti Angelo Ranieri Cecilia Camarda Rosario Vecchio Valeria Drago Giulia Fiorentini Carlo Tomino Stefano Bonassi Paola Torelli Alice Mannocci for the Italian Migraine Registry (I-GRAINE) study group |
| author_sort | Piero Barbanti |
| collection | DOAJ |
| description | Abstract Background Atogepant, the first oral CGRP receptor antagonist approved for migraine prevention, has demonstrated efficacy and safety in randomized clinical trials (RCT). However, prospective real-world data are lacking. Objective To explore the effectiveness, safety, and tolerability of atogepant 60 mg at week 12 in patients with high-frequency episodic (HFEM: 8-14 days/month) or chronic migraine (CM) with multiple therapeutic failures. Methods This ongoing, multicenter (n = 16), prospective real-world study included consecutive adults with HFEM or CM who had failed ≥3 prior preventive treatments, according to AIFA criteria. Participants received atogepant 60 mg daily, with treatment planned for up to 12 months. Primary endpoint: change from baseline to week 12 in monthly migraine days (MMD) for HFEM and monthly headache days (MHD) for CM. Secondary endpoints: changes in monthly analgesic intake (MAI), pain intensity (NRS), disability (HIT-6, MIDAS), interictal burden (MIBS-4), treatment satisfaction (PGIC), responder rates (≥ 50%, ≥ 75%, 100%), and changes in migraine frequency during the first treatment week compared to the last pre-treatment week. Adverse events were monitored throughout. Results A total of 183 patients were enrolled and 82 completed ≥ 12 weeks of follow-up. Of these, 41.5% had previously failed anti-CGRP mAbs. At week 12, significant reductions (p < 0.001) were observed in MMD (–6.0) and MHD (–11.2). Secondary outcomes also improved significantly (p < 0.001): MAI (–10.9), NRS (–2.7), HIT-6 (–13.2), MIDAS (–61.1), and MIBS-4 (–5.4). Responder rates were 65.9% (≥ 50%), 36.6% (≥ 75%), and 6.1% (100%). PGIC documented high satisfaction (much/very much improved: 70.7%). A significant decrease (p < 0.001) in migraine frequency was already evident by week 1 (overall: − 2.5 days, HFEM: − 1.5, CM: − 3.1). In the mAb-failure subgroup, ≥ 50% and ≥ 75% response rates were 52.9% and 23.5%, with significant improvements in all primary and secondary endpoints (p < 0.001). Adverse events occurred in 5.5% of patients, and 1.6% discontinued treatment. Conclusion The GIANT study provides real-world evidence of atogepant’s effectiveness, safety, and tolerability in patients with HFEM and CM with multiple therapeutic failures and comorbidities. It extends RCT data by showing rapid onset of action, meaningful reductions in pain intensity and interictal disability, high patient satisfaction, and effectiveness even in patients with anti-CGRP mAb failures. |
| format | Article |
| id | doaj-art-945e703f484e4db8a5596892a10c122b |
| institution | DOAJ |
| issn | 1129-2377 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | The Journal of Headache and Pain |
| spelling | doaj-art-945e703f484e4db8a5596892a10c122b2025-08-20T03:08:43ZengBMCThe Journal of Headache and Pain1129-23772025-05-0126111210.1186/s10194-025-02068-2GIANT: a prospective, multicenter, real-world study on the effectiveness, safety, and tolerability of atogepant in migraine patients with multiple therapeutic failuresPiero Barbanti0Gabriella Egeo1Francesca Pistoia2Cinzia Aurilia3Paola Scatena4Steno Rinalduzzi5Silvia Strumia6Antonio Salerno7Fabio Frediani8Andrea Galli9Massimo Autunno10Laura Di Clemente11Maurizio Zucco12Maria Albanese13Francesco Bono14Pietrantonio Bruno15Laura Borrello16Stefano Messina17Alberto Doretti18Angelo Ranieri19Cecilia Camarda20Rosario Vecchio21Valeria Drago22Giulia Fiorentini23Carlo Tomino24Stefano Bonassi25Paola Torelli26Alice Mannocci27for the Italian Migraine Registry (I-GRAINE) study group28Headache and Pain Unit, IRCCS San Raffaele RomeHeadache and Pain Unit, IRCCS San Raffaele RomeDepartment of Biotechnological and Applied Clinical Sciences, University of L’AquilaHeadache and Pain Unit, IRCCS San Raffaele RomeDepartment of Neurology and Stroke Unit, San Camillo de Lellis, General District HospitalDepartment of Neurology and Stroke Unit, San Camillo de Lellis, General District HospitalDepartment of Neurology, G.B. Morgagni L. Pierantoni HospitalHeadache Center, San Giovanni Addolorata HospitalStroke Unit, Neurology Division, and Headache Center, San Carlo Borromeo Hospital, ASST Santi Paolo e CarloStroke Unit, Neurology Division, and Headache Center, San Carlo Borromeo Hospital, ASST Santi Paolo e CarloDepartment of Clinical and Experimental Medicine, University of MessinaHeadache Center, Neurology Unit, San Camillo-Forlanini HospitalHeadache Center, Neurology Unit, San Camillo-Forlanini HospitalDepartment of Systems Medicine, University of Rome Tor VergataCenter for Headache and Intracranial Pressure Disorders, Neurology Unit, A.O.U. Mater DominiCenter for Headache and Intracranial Pressure Disorders, Neurology Unit, A.O.U. Mater DominiHeadache Center, Francesco Spaziani HospitalDepartment of Neurology and Laboratory of Neuroscience, Istituto Auxologico Italiano, IRCCSDepartment of Neurology and Laboratory of Neuroscience, Istituto Auxologico Italiano, IRCCSHeadache Centre, Division of Neurology and Stroke-Unit, Antonio Cardarelli HospitalDepartment of Biomedicine, Neurosciences, and Advanced Diagnostics, University of PalermoNeurology Unit Muscatello Hospital Augusta ASP SiracusaNeurology Unit Muscatello Hospital Augusta ASP SiracusaHeadache and Pain Unit, IRCCS San Raffaele RomeIRCCS San RaffaeleDepartment for the Promotion of Human Sciences and Quality of Life, San Raffaele UniversityDepartment of Medicine and Surgery, Headache Center, Neurology Unit, University of ParmaDepartment for the Promotion of Human Sciences and Quality of Life, San Raffaele UniversityHeadache and Pain Unit, IRCCS San Raffaele RomeAbstract Background Atogepant, the first oral CGRP receptor antagonist approved for migraine prevention, has demonstrated efficacy and safety in randomized clinical trials (RCT). However, prospective real-world data are lacking. Objective To explore the effectiveness, safety, and tolerability of atogepant 60 mg at week 12 in patients with high-frequency episodic (HFEM: 8-14 days/month) or chronic migraine (CM) with multiple therapeutic failures. Methods This ongoing, multicenter (n = 16), prospective real-world study included consecutive adults with HFEM or CM who had failed ≥3 prior preventive treatments, according to AIFA criteria. Participants received atogepant 60 mg daily, with treatment planned for up to 12 months. Primary endpoint: change from baseline to week 12 in monthly migraine days (MMD) for HFEM and monthly headache days (MHD) for CM. Secondary endpoints: changes in monthly analgesic intake (MAI), pain intensity (NRS), disability (HIT-6, MIDAS), interictal burden (MIBS-4), treatment satisfaction (PGIC), responder rates (≥ 50%, ≥ 75%, 100%), and changes in migraine frequency during the first treatment week compared to the last pre-treatment week. Adverse events were monitored throughout. Results A total of 183 patients were enrolled and 82 completed ≥ 12 weeks of follow-up. Of these, 41.5% had previously failed anti-CGRP mAbs. At week 12, significant reductions (p < 0.001) were observed in MMD (–6.0) and MHD (–11.2). Secondary outcomes also improved significantly (p < 0.001): MAI (–10.9), NRS (–2.7), HIT-6 (–13.2), MIDAS (–61.1), and MIBS-4 (–5.4). Responder rates were 65.9% (≥ 50%), 36.6% (≥ 75%), and 6.1% (100%). PGIC documented high satisfaction (much/very much improved: 70.7%). A significant decrease (p < 0.001) in migraine frequency was already evident by week 1 (overall: − 2.5 days, HFEM: − 1.5, CM: − 3.1). In the mAb-failure subgroup, ≥ 50% and ≥ 75% response rates were 52.9% and 23.5%, with significant improvements in all primary and secondary endpoints (p < 0.001). Adverse events occurred in 5.5% of patients, and 1.6% discontinued treatment. Conclusion The GIANT study provides real-world evidence of atogepant’s effectiveness, safety, and tolerability in patients with HFEM and CM with multiple therapeutic failures and comorbidities. It extends RCT data by showing rapid onset of action, meaningful reductions in pain intensity and interictal disability, high patient satisfaction, and effectiveness even in patients with anti-CGRP mAb failures.https://doi.org/10.1186/s10194-025-02068-2AtogepantMigraineCGRPTreatmentReal-worldDisability |
| spellingShingle | Piero Barbanti Gabriella Egeo Francesca Pistoia Cinzia Aurilia Paola Scatena Steno Rinalduzzi Silvia Strumia Antonio Salerno Fabio Frediani Andrea Galli Massimo Autunno Laura Di Clemente Maurizio Zucco Maria Albanese Francesco Bono Pietrantonio Bruno Laura Borrello Stefano Messina Alberto Doretti Angelo Ranieri Cecilia Camarda Rosario Vecchio Valeria Drago Giulia Fiorentini Carlo Tomino Stefano Bonassi Paola Torelli Alice Mannocci for the Italian Migraine Registry (I-GRAINE) study group GIANT: a prospective, multicenter, real-world study on the effectiveness, safety, and tolerability of atogepant in migraine patients with multiple therapeutic failures The Journal of Headache and Pain Atogepant Migraine CGRP Treatment Real-world Disability |
| title | GIANT: a prospective, multicenter, real-world study on the effectiveness, safety, and tolerability of atogepant in migraine patients with multiple therapeutic failures |
| title_full | GIANT: a prospective, multicenter, real-world study on the effectiveness, safety, and tolerability of atogepant in migraine patients with multiple therapeutic failures |
| title_fullStr | GIANT: a prospective, multicenter, real-world study on the effectiveness, safety, and tolerability of atogepant in migraine patients with multiple therapeutic failures |
| title_full_unstemmed | GIANT: a prospective, multicenter, real-world study on the effectiveness, safety, and tolerability of atogepant in migraine patients with multiple therapeutic failures |
| title_short | GIANT: a prospective, multicenter, real-world study on the effectiveness, safety, and tolerability of atogepant in migraine patients with multiple therapeutic failures |
| title_sort | giant a prospective multicenter real world study on the effectiveness safety and tolerability of atogepant in migraine patients with multiple therapeutic failures |
| topic | Atogepant Migraine CGRP Treatment Real-world Disability |
| url | https://doi.org/10.1186/s10194-025-02068-2 |
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