Headache, Headache (Migraine), Migraine, Migraine Disability, Migraine Disease, Migraine Disorder, Migraine Headache
Conditions
Keywords
Migraine, Atogepant, CGRP, anti-CGRP, Gepant, Headache, Long-term, Preventive treatment, Real-world evidence, Real-world, Treatment resistance, Chronic migraine, Refractory migraine, Resistant migraine, Treatment-resistant migraine, Medication overuse, Gepants, Calcitonin gene-related peptide, CGRP pathway, Oral CGRP antagonist, Preventive migraine therapy, Preventive therapy, Migraine prevention, Real-world study, Mutlicentre study, Observational study, Prospective study, Long-term effectiveness, Long-term safety, Tolerability, Effectiveness, Safety, Adverse events, Monthly headache days, MHD, MMD, Monthly migraine days, HIT-6, HADS, ISI, Treatment response, Patient-reported outcomes
Brief 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.
Detailed description
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
DRUGAtogepant 60 mg
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.
OTHERHeadache diary
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.
Sponsors
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Hospital Universitario de Fuenlabrada
Fundación Jimenez Diaz de Madrid
Hospital Virgen del Puerto
Hospital San Carlos, Madrid
Hospital Universitario 12 de Octubre
Hospital Clínico Universitario de Valladolid
Hospital Universitario Fundación Alcorcón
Hospital General Universitario Gregorio Marañon
Hospital Universitario La Paz
Hospital Son Espases
Hospital Clínico Universitario Lozano Blesa
Hospital Universitario Getafe
Hospital Torrejón de Ardoz
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in monthly headache days (MHD) | 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). | 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. | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterization of sustained, late, and ultra-late treatment response | 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 | 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 | 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 | 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 | 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 | 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 | 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). |
Countries
Spain
Contacts
PRINCIPAL_INVESTIGATORAna B Gago-Veiga
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Outcome results
None listed