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Background and Importance Atogepant inhibits calcitonin gene-related peptide (CGRP) receptors involved in migraine development.Aim and Objectives To evaluate atogepant effectiveness, quality of life and safety for adult migraine prophylaxis. Secondary endpoint: to assess atogepant effectiveness as third-line treatment in patients with prior failure of anti-CGRP monoclonal antibodies (mAb-antiCGRP).Material and Methods One-year ambispective longitudinal study of patients initiating atogepant (July 2024-2025). Approved by the Ethics Committee in collaboration with the Neurology Department. Data were analysed with Wilcoxon and Mann–Whitney-U tests in STATA v.16.0.Data collected: demographics, migraine classification and previous preventive treatment (PPT). Prospective follow-up at weeks 0 and 12 assessed migraine days/month (MDM), acute treatment days/month (TDM), intensity (0-10) and Headache Impact Test (HIT-6≥60=very severe impact). Adverse events (AEs) and treatment discontinuation.Primary effectiveness variable: median MDM reduction. Secondary variables:% responders (≥1-day MDM reduction) and% patients with ≥50% MDM reduction (50% MDM). Quality of life:% patients with ≥5 HIT-6 reduction.Results Forty-two patients (81% women), median age of 49 years (IQR: 41-55), 81% with chronic migraine (CM). Median PPT was 6 (IQR: 5-8): antidepressants (95%), antiepileptics (95%), botulinum toxin (83%), beta-blockers (71%) and calcium-antagonists (64%). The 64% (n=27) previously received mAb-antiCGRP: 2 (IQR:1-3). Median duration was 22 weeks (IQR:15-34), 18 patients discontinued (15 therapeutic failure, 3 AEs).The 90% (n=38) reached 12 weeks of treatment. MDM median baseline was 23 days (IQR:13-30) vs 10 (IQR:3-30) post-12 weeks, (p=0.0001). A 58% (n=22) were responders, with a median MDM reduction of -10 (IQR:-13-(-6)). Of these, 50% (n=11) were third-line responders, with no difference in MDM reduction by prior mAb-antiCGRP failure (p=0.125).TDM median baseline vs post-12 weeks was 20 (IQR:13-30) vs 7 (IQR: 3-20) (p=0.0001), intensity 9 (IQR: 8-10) vs 8 (IQR: 6-9) (p=0.0043) and HIT-6 72 (IQR: 65-76) vs 63 (IQR: 56-72) (p=0.0002), respectively. The 50% (n=19) achieved ≥50% MDM and 53% (n=20) reduced ≥5 HIT-6.The 64% (n=27) experienced AEs: constipation (33%), fatigue (31%), nausea (29%) and weight loss (17%).Conclusion and Relevance Most patients were women with CM and prior mAb–antiCGRP failure.Atogepant led to a significant but modest MDM/TDM reduction, consistent with pivotal trials.In responders, prior mAb–antiCGRP failure did not appear to worsen atogepant response.Half achieved ≥50% MDM, though quality of life impact remained very severe.AEs were frequent but generally mild and manageable.Conflict of Interest No conflict of interest