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Background and Importance Atogepant is indicated for the preventive treatment of chronic migraine (CM), a highly prevalent and disabling neurological disorder. It is an orally administered drug that blocks the calcitonin gene-related peptide (CGRP) receptor. In our healthcare setting, it is funded for patients who have failed ≥3 prior prophylactic treatments and who experience ≥8 monthly migraine days (MMD).Aim and Objectives The aim of this study was to evaluate the effectiveness and tolerability of atogepant in real-world clinical practice in CM patients who had previously received another anti-CGRP drug, a cohort not represented in clinical trials.Material and Methods Retrospective and observational study conducted at a tertiary hospital. We identified all CM patients who started treatment with atogepant between 04/2024–06/2025. We collected demographic (age, sex, comorbidities) and clinical data (MMD at baseline and at 3 months of follow-up, prior treatments, reason for discontinuation, and adverse events (AEs)).Results A total of 54 CM patients receiving atogepant were identified during the study period. Of them, 87% (n=47) were women and mean age was 50 years (range 23–79 years). The two most frequent comorbidities were anxiety (51.8%, n=28) and insomnia (35.2%, n=19). Patients had received a mean of 6.6±2.9 preventive treatments prior to the first anti-CGRP therapy. Twenty-eight patients (51.8%) had received ≥3 prior anti-CGRP treatments. At 3-months follow-up (n=35): a 74.3% of patients (n=26) had no improvement in MMD and a 25.7% (n=9) had a reduction in MMD (mean reduction: 3.6±1.8 days). During the study period, 30 patients (55.6%) discontinued atogepant. The mean duration until discontinuation was 2.7±1.7 months. The main reasons for discontinuation were: ineffectiveness (40.0%, n=12), AEs (33.3%, n=10), and both ineffectiveness and AEs (10.0%, n=3). Regarding the 13 cases of discontinuation related to intolerance, the AEs reported (patients could present more than one effect) were constipation (n=5), asthenia (n=3), gastrointestinal discomfort (n=3), dizziness (n=2), and allergic reactions (n=1).Conclusion and Relevance The effectiveness of atogepant in patients pretreated with anti-CGRP therapies is limited, and tolerability issues led to treatment discontinuation in a relevant proportion of cases. It is necessary to determine the clinical benefit of atogepant in patients refractory to previous anti-CGRP treatments.Conflict of Interest No conflict of interest