Status
Completed
Phase
Not applicable
Enrollment
513
Locations
1
Results
Not posted
Publications
1
Study summary
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.
Interventions
DRUG
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.
OTHER
Patients systematically recorded monthly headache days, monthly migraine days, and use of acute medication throughout follow-up.
OTHER
Patients completed standardized validated questionnaires including HIT-6, HADS, and ISI at predefined follow-up visits to assess migraine-related disability and associated comorbidities.
Timeline
First posted
Jul 13, 2026
Study start
Jun 1, 2024
Primary completion
Mar 1, 2026
Study completion
Mar 1, 2026
Results posted
Not reported
Registry updated
Jul 22, 2026
Outcomes
Change from baseline in monthly headache days (MHD)
Time frame · From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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.
Change from baseline in monthly migraine days (MMD).
Time frame · From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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.
Proportion of patients achieving ≥30%, ≥50%, ≥75%, and 100% response rates over 12 months.
Time frame · From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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.
Persistence of treatment response
Time frame · From baseline (initiation of atogepant treatment) to 12 months of follow-up.
Persistence of treatment response will be assessed as the proportion of patients who maintain their clinical response between Months 6 and 12.
Characterization of sustained, late, and ultra-late treatment response
Time frame · From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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.
Changes in migraine-related disability - HIT-6
Time frame · From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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.
Changes in psychiatric comorbidities - HADS
Time frame · From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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.
Changes in migraine-related comorbidities - ISI
Time frame · From baseline (initiation of atogepant treatment) to 12 months of follow-up.
Insomnia Severity Index (ISI) total score will be assessed at baseline and during follow-up in the subset of patients with available data.
Clinical predictors of sustained response at 12 months
Time frame · From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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).
Impact of prior exposure to anti-CGRP monoclonal antibodies on treatment response
Time frame · From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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).
Long-term safety of atogepant
Time frame · From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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).
Eligibility
Inclusion Criteria: * Adults aged ≥18 years. * Diagnosis of migraine with or without aura established by a headache specialist according to the International Classification of Headache Disorders, 3rd edition (ICHD-3), including both chronic and episodic migraine. * History of migraine of at least 1 year duration. * Stable preventive migraine treatment (if any) for at least the previous 3 months. * Normal neurological examination. * Fulfilment of national health system reimbursement criteria for atogepant treatment. Exclusion Criteria: * Cognitive impairment or any other condition that, in the investigator's opinion, may prevent the patient from reliably distinguishing prodromal symptoms. * Presence of other active primary or secondary headache disorders, except medication overuse headache or infrequent tension-type headache.
Study locations
Spain. Showing up to 24 locations stored in the fast local snapshot.
Hospital Universitario de La Princesa
Madrid, Madrid, Spain
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