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

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. 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. 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. 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. This is the largest real-world study to date evaluating atogepant after failure of anti-CGRP monoclonal antibodies in migraine, including a highly refractory multicenter cohort. Atogepant after anti-CGRP monoclonal antibodies failure achieved a ≥ 50% response in 29.7% of patients and a ≥ 30% response in 44.4% at 3 months, with mild adverse effects reported in over half of cases. A higher number of previously failed MAbs, trigeminoautonomic symptoms, and depression were independently associated with lower likelihood of response.