Atogepant after anti-CGRP monoclonal antibodies failure in migraine: a multicenter real-world study of effectiveness, safety, persistence and predictors of response

Abstract

Background: Atogepant is approved for migraine prevention and has shown strong efficacy in clinical trials. However, its effectiveness following failure of anti-CGRP monoclonal antibodies (MAbs) has not been evaluated in large real-world populations. Methods: This multicenter observational study conducted across Spanish headache units included adults with migraine who initiated atogepant after failure of ≥ 1 anti-CGRP MAb and had ≥ 3 months of follow-up. Baseline demographic and clinical variables were collected prospectively, with follow-up assessments at months 3 and 6. The primary outcome was the proportion of patients achieving a ≥ 50% reduction in monthly migraine days (MMD) at three months. Secondary outcomes included ≥ 30%, ≥ 75%, and 100% response rates; changes in headache days, pain intensity, acute medication use, and patient-reported outcomes; adverse events; treatment persistence; and factors associated with response. Results: A total of 252 patients were included (mean age 48.9 ± 12 years; 83.3% female; 80.6% with chronic migraine; 45.6% with continuous daily headache). Prior to atogepant, 39.7% had failed one anti-CGRP MAb, 27.0% two, 20.2% three, and 13.1% four. Median baseline MMD was 16, monthly headache days 27, and acute medication days 20. At 3 months, 44.4% achieved a ≥ 30% reduction in MMD, 29.7% ≥50%, and 11.7% ≥75%. Adverse events were reported in 52.5% of patients, most commonly constipation (30%) and nausea (25%). At three months, 26.2% had discontinued treatment (65.1% due to inefficacy, 28.8% due to intolerance). Treatment persistence at 180 days was 61% (95% CI 54 to 69%). A higher number of previously failed MAbs was independently associated with reduced odds of ≥ 50% response (RR 0.79, 95% CI 0.64 to 0.97). Moreover, a higher number of previously failed MAbs was associated with diminished improvements across multiple clinical endpoints, including headache frequency, intensity, acute medication use, and disability measures. Conclusion: Atogepant may represent a viable treatment option for patients with migraine who have failed anti-CGRP MAbs. In this large real-world cohort, approximately one-third of patients achieved a ≥ 50% response, despite a treatment-refractory profile. However, the likelihood of response decreases with a higher number of previously failed MAbs, and mild adverse events are frequent.