This prospective multicentre observational study aims to evaluate the long-term effectiveness, safety, tolerability, and treatment persistence of atogepant for migraine prevention in routine clinical practice. Adult patients with migraine initiating atogepant across 15 tertiary Headache Units in Spain are followed for 12 months. Clinical outcomes, including monthly headache days, monthly migraine days, medication overuse, adverse events, treatment discontinuation, and patient-reported outcomes in a subset of participants, are assessed at baseline and after 3, 6, and 12 months. The study also characterizes different response trajectories, including sustained, delayed, and transient responses, in a real-world population with high disease burden and multiple prior preventive treatment failures.
Preventive migraine therapies targeting the calcitonin gene-related peptide (CGRP) pathway have transformed clinical practice, particularly monoclonal antibodies and, more recently, gepants. Atogepant, an oral CGRP receptor antagonist, has demonstrated efficacy and safety in randomized controlled trials and extensions across episodic, chronic, and treatment-refractory migraine populations. However, these studies are based on highly selected cohorts with limited external validity. In routine clinical practice, patients present with high disease burden, multiple preventive treatment failures, prior exposure to CGRP-targeted therapies, medication overuse, and psychiatric comorbidities, all of which may influence outcomes. Although short- and mid-term real-world data support clinically meaningful benefit within 3-6 months, evidence beyond this period remains limited, particularly regarding long-term effectiveness, tolerability, and treatment persistence, as well as sustained, delayed, or transient response trajectories. This prospective multicentre observational study was conducted within the GEMA (GEpants in MigrAine-Atogepant) Project across 15 tertiary Headache Units in Spain. Adults with migraine initiating atogepant in routine clinical practice were consecutively enrolled between June 2024 and March 2025 and followed for 12 months. Data were collected at baseline and at 3, 6, and 12 months using standardized REDCap case report forms through structured interviews. Variables included sociodemographic and clinical characteristics, migraine phenotype, disease duration, prior preventive treatment failures, concomitant preventive therapies, monthly headache days (MHD), monthly migraine days (MMD), analgesic overuse, adverse events, and treatment discontinuation. Definitions were based on ICHD-3 criteria. In a subset, patient-reported outcomes were assessed using validated instruments: Headache Impact Test (HIT-6), Hospital Anxiety and Depression Scale (HADS), and Insomnia Severity Index (ISI). Analyses were performed using both all-available-observation and complete-case approaches, without imputation of missing outcome data.
Study Type
OBSERVATIONAL
Enrollment
513
Atogepant was administered as preventive treatment for migraine in routine clinical practice. Treatment initiation, dose selection, dose modifications, and discontinuation were determined by the treating physician according to the approved prescribing information and routine clinical practice. As this was an observational study, no study-specific intervention or randomization was performed.
Patients systematically recorded monthly headache days, monthly migraine days, and use of acute medication throughout follow-up.
Patients completed standardized validated questionnaires including HIT-6, HADS, and ISI at predefined follow-up visits to assess migraine-related disability and associated comorbidities.
Hospital Universitario de La Princesa
Madrid, Madrid, Spain
Change from baseline in monthly headache days (MHD)
Monthly headache days (MHD) will be assessed at baseline and after 3, 6, and 12 months of atogepant treatment to evaluate clinical effectiveness in routine clinical practice.
Time frame: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
Change from baseline in monthly migraine days (MMD).
Monthly migraine days (MMD) will be assessed at baseline and after 3, 6, and 12 months of atogepant treatment to evaluate clinical effectiveness in routine clinical practice.
Time frame: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
Proportion of patients achieving ≥30%, ≥50%, ≥75%, and 100% response rates over 12 months.
The proportion of patients achieving ≥30%, ≥50%, ≥75%, and 100% reduction from baseline in monthly headache days (MHD) and monthly migraine days (MMD) will be assessed over 12 months.
Time frame: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
Persistence of treatment response
Persistence of treatment response will be assessed as the proportion of patients who maintain their clinical response between Months 6 and 12.
Time frame: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
Characterization of sustained, late, and ultra-late treatment response
Patients will be classified as sustained, late, or ultra-late responders according to the predefined response criteria, and the proportion of patients in each response category will be assessed over 12 months.
Time frame: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
Changes in migraine-related disability - HIT-6
Headache Impact Test-6 (HIT-6) total score will be assessed at baseline and during follow-up in the subset of patients with available data.
Time frame: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
Changes in psychiatric comorbidities - HADS
Hospital Anxiety and Depression Scale (HADS) total score will be assessed at baseline and during follow-up in the subset of patients with available data.
Time frame: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
Changes in migraine-related comorbidities - ISI
Insomnia Severity Index (ISI) total score will be assessed at baseline and during follow-up in the subset of patients with available data.
Time frame: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
Clinical predictors of sustained response at 12 months
Baseline clinical characteristics associated with sustained response at Month 12 will be evaluated. Sustained response will be defined as achieving a ≥50% reduction from baseline in monthly headache days (MHD) and monthly migraine days (MMD).
Time frame: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
Impact of prior exposure to anti-CGRP monoclonal antibodies on treatment response
Treatment response will be compared according to prior anti-CGRP monoclonal antibody exposure, number of prior anti-CGRP monoclonal antibodies, and prior target (ligand vs receptor).
Time frame: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
Long-term safety of atogepant
Long-term safety will be assessed by recording adverse events, treatment discontinuation, and reasons for treatment discontinuation over 12 months, stratified by follow-up interval (0-3, 3-6, and 6-12 months).
Time frame: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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