Barbanti Piero, Egeo Gabriella, Pistoia Francesca, Aurilia Cinzia, Scatena Paola, Rinalduzzi Steno, Strumia Silvia, Salerno Antonio, Frediani Fabio, Galli Andrea, Autunno Massimo, Di Clemente Laura, Zucco Maurizio, Albanese Maria, Bono Francesco, Bruno Pietrantonio, Borrello Laura, Messina Stefano, Doretti Alberto, Ranieri Angelo, Camarda Cecilia, Vecchio Rosario, Drago Valeria, Fiorentini Giulia, Tomino Carlo, Bonassi Stefano, Torelli Paola, Mannocci Alice
Headache and Pain Unit, IRCCS San Raffaele Rome, Rome, Italy.
Department for the Promotion of Human Sciences and Quality of Life, San Raffaele University, Rome, Italy.
J Headache Pain. 2025 May 19;26(1):122. doi: 10.1186/s10194-025-02068-2.
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.
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.
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.
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.
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.
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.
阿托格潘是首个被批准用于预防偏头痛的口服降钙素基因相关肽（CGRP）受体拮抗剂，已在随机临床试验（RCT）中证明了其有效性和安全性。然而，前瞻性的真实世界数据尚缺。
探讨12周时60毫克阿托格潘对高频发作性（HFEM：每月8 - 14天）或慢性偏头痛（CM）且有多次治疗失败经历的患者的有效性、安全性及耐受性。
这项正在进行的多中心（n = 16）前瞻性真实世界研究纳入了符合意大利药品管理局（AIFA）标准、先前接受≥3种预防性治疗均失败的HFEM或CM成年患者。参与者每日服用60毫克阿托格潘，计划治疗长达12个月。
HFEM患者每月偏头痛天数（MMD）以及CM患者每月头痛天数（MHD）从基线到第12周的变化。次要终点：每月镇痛药摄入量（MAI）、疼痛强度（数字评分量表，NRS）、残疾程度（头痛影响测试-6，HIT-6；偏头痛残疾评定量表，MIDAS）、发作间期负担（偏头痛发作间期负担量表-4，MIBS-4）、治疗满意度（患者整体印象变化量表，PGIC）、缓解率（≥50%、≥75%、100%），以及与治疗前最后一周相比，治疗第一周偏头痛频率变化。全程监测不良事件。
共纳入183例患者，82例完成了≥12周的随访。其中，41.5%的患者先前抗CGRP单克隆抗体治疗失败。在第12周时，观察到MMD（-6.0）和MHD（-11.2）显著降低（p < 0.001）。次要结局也显著改善（p < 0.001）：MAI（-10.9）、NRS（-2.7）、HIT-6（-13.2）、MIDAS（-61.1）和MIBS-4（-5.4）。缓解率分别为65.9%（≥50%）、36.6%（≥75%）和6.1%（100%）。PGIC显示患者满意度高（改善很多/非常多：70.7%）。到第1周时，偏头痛频率已显著下降（p < 0.001）（总体：-2.5天，HFEM：-1.5天，CM：-3.1天）。在单克隆抗体治疗失败亚组中，≥50%和≥75%的缓解率分别为52.9%和23.5%，所有主要和次要终点均有显著改善（p < 0.001）。5.5%的患者发生不良事件，1.6%的患者停止治疗。
GIANT研究提供了真实世界证据，证明阿托格潘对有多次治疗失败经历和合并症的HFEM和CM患者有效、安全且耐受性良好。该研究扩展了随机临床试验数据，显示出起效迅速、疼痛强度和发作间期残疾程度显著降低、患者满意度高，甚至在抗CGRP单克隆抗体治疗失败的患者中也有效。
