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Multicenter Study
. 2025 May 19;26(1):122.
doi: 10.1186/s10194-025-02068-2.

GIANT: a prospective, multicenter, real-world study on the effectiveness, safety, and tolerability of atogepant in migraine patients with multiple therapeutic failures

Piero Barbanti #  1   2 , Gabriella Egeo #  3 , Francesca Pistoia  4 , Cinzia Aurilia  3 , Paola Scatena  5 , Steno Rinalduzzi  5 , Silvia Strumia  6 , Antonio Salerno  7 , Fabio Frediani  8 , Andrea Galli  8 , Massimo Autunno  9 , Laura Di Clemente  10 , Maurizio Zucco  10 , Maria Albanese  11 , Francesco Bono  12 , Pietrantonio Bruno  12 , Laura Borrello  13 , Stefano Messina  14 , Alberto Doretti  14 , Angelo Ranieri  15 , Cecilia Camarda  16 , Rosario Vecchio  17 , Valeria Drago  17 , Giulia Fiorentini  3 , Carlo Tomino  18 , Stefano Bonassi  19   20 , Paola Torelli #  21 , Alice Mannocci #  19   20 ; Italian Migraine Registry (I-GRAINE) study group
Collaborators, Affiliations
Multicenter Study

GIANT: a prospective, multicenter, real-world study on the effectiveness, safety, and tolerability of atogepant in migraine patients with multiple therapeutic failures

Piero Barbanti et al. J Headache Pain. .

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.

Keywords: Atogepant; CGRP; Disability; Migraine; Real-world; Treatment.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All patients provided written informed consent prior to participation. The study was conducted in accordance with the Declaration of Helsinki, approved by the Lazio 5 Institutional Review Board (approval number 0003898), and mutually recognized by the ethics committees of all participating centers. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Patients’ disposition
Fig. 2
Fig. 2
Change in monthly migraine days (MMD) for subjects with patients with high-frequency episodic migraine (HFEM) and in monthly headache days (MHD) for those with chronic migraine (CM) at weeks 9–12, compared to baseline
Fig. 3
Fig. 3
Response rates at weeks 9–12. All: total patient population; HFEM: patients with high-frequency episodic migraine; CM: patients with chronic migraine. ≥ 50% responders: proportion of patients with a ≥ 50% reduction in monthly migraine/headache days compared to baseline; ≥ 75% responders: proportion of patients with a ≥ 75% reduction in monthly migraine/headache days compared to baseline; 100% responders: proportion of patients with a 100% reduction in monthly migraine/headache days compared to baseline
Fig. 4
Fig. 4
Patient Global Impression of Change (PGIC) at weeks 9–12 in the overall patient population (all patients; n = 82, blue bars), in patients with prior failure to monoclonal antibodies targeting CGRP pathway (anti-CGRP mAbs; n = 34, gray bars)
Fig. 5
Fig. 5
Response rates at weeks 9–12 in the overall migraine population (all patients, n = 82), patients naïve to anti-CGRP mAbs (n = 48) and individuals with prior anti-CGRP mAb failures (n = 34). ≥ 50% responders: proportion of patients with a ≥ 50% reduction in monthly migraine/headache days compared to baseline; ≥ 75% responders: proportion of patients with a ≥ 75% reduction in monthly migraine/headache days compared to baseline; 100% responders: proportion of patients with a 100% reduction in monthly migraine/headache days compared to baseline
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