Effectiveness and tolerability of atogepant in the prevention of migraine: A real life, prospective, multicentric study (the STAR study)

Background: Focusing on calcitonin gene-related peptide (CGRP) as a specific target has changed and improved migraine management. After the positive results of monoclonal antibodies directed to the CGRP pathway (anti-CGRP mAbs), randomized controlled trials also demonstrated the efficacy of gepants in migraine prevention. The present study aimed to assess the effectiveness of atogepant in preventing migraine after a 12-week treatment in clinical practice. Methods: Adult patients with a clinical indication for atogepant 60 mg daily were screened for participation in this multicentric prospective observational cohort study. At baseline (T0) and after 12 weeks (T3) since the first atogepant administration, monthly migraine days (MMDs), monthly headache days (MHDs) and monthly acute medications (MAMs) were assessed. The co-primary endpoints were the changes in MMDs from T0 to T3 and the percentage of T3 Responders (those with a reduction of MMDs ≥50%, i.e. 50% response rate (RR)). At T0 and T3, we also collected the Headache Impact Test (HIT-6), the Migraine Disability Assessment (MIDAS) questionnaire, the Migraine Treatment Optimization Questionnaire-6 (mTOQ-6), the Migraine-Specific Quality-of-Life Questionnaire (MSQ), the 12-item Allodynia Symptom Checklist (ASC-12) and the Migraine Interictal Burden Scale (MIBS-4). Results: One hundred and six patients (56/106 (52.8%) with chronic migraine (CM), 93/106 (87.7%) female, aged 50.6 ± 13.2 years) from 10 Italian centers completed the 12-week observation since the first atogepant tablet intake. From baseline to T3, a reduction of 6.9 MMDs (SD 9.7; p < 0.001) was achieved in the whole group and, specifically, of −4.9 (SD 6.6; p < 0.001) in episodic migraine (EM) and of −8.6 (SD 11.7; p < 0.001) in CM patients. Overall, 60/106 (56.6%) of patients were Responders (60.0% in the EM and 46.4% in the CM group). Non-Responders previously experienced more ineffective treatments than Responders with anti-CGRP mAbs (65.2% vs. 43.3%, respectively, p = 0.031) and with onabotulinumtoxinA (56.5% vs. 28.3%, p = 0.005), and presented more medication overuse at baseline (55.7% vs. 44.3%, p = 0.003). However, no baseline characteristics were significantly associated with the Responder status in the multiple regression analysis. For T0 to T3, MAMs, MIDAS, ASC-12 and mTOQ-6 reduced (p ≤ 0.001 consistently), and MSQ role-function restriction increased (p = 0.026), whereas HIT-6 and MIBS-4 did not change. Only seven subjects (7/106, 6.6%) dropped out of atogepant treatment: four for lack of effectiveness and three for adverse events or poor tolerability. Conclusions: The STAR study demonstrates the effectiveness and tolerability of atogepant 60 mg at 12 weeks in a real-world setting. Previous ineffective anti-CGRP mAbs were not a relevant prognostic factor. Trial Registration: The study was preregistered on clinicaltrial.gov, NCT06414044.