Long-term Atogepant in Real-world Practice (GEMA PROJECT)
Long-term Atogepant for Treatment-resistant Migraine in Real-world Clinical Practice: 12-month Result
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Inscription (Réel)
Contacts et emplacements
Lieux d'étude
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Madrid
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Madrid, Madrid, Espagne, 28006
- Hospital Universitario de La Princesa
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
Méthode d'échantillonnage
Population étudiée
Adult patients with migraine, according to ICHD-3 criteria, initiating preventive treatment with atogepant in routine clinical practice were included in this prospective, multicentre, open-label observational study. No masking was applied. Patients were recruited from headache units and neurology departments across Spain:
- Hospital Universitario de La Princesa
- Hospital Universitario de Fuenlabrada
- Fundación Jiménez Díaz-UTE
- Hospital de Torrejón
- Hospital Virgen del Puerto
- Hospital Clínico San Carlos
- Hospital Universitario 12 de Octubre
- Hospital Clínico Universitario de Valladolid (IBIoVALL)
- Hospital Universitario La Paz
- Hospital Clínico Universitario Lozano Blesa
- Hospital Universitario de Getafe
- Hospital Ruber Internacional Treatment initiation with atogepant for migraine prevention was determined by the treating neurologist according to clinical practice guidelines and standard of care.
La description
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.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
Intervention / Traitement |
|---|---|
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Migraine cohort
Adult patients with migraine initiating atogepant for preventive treatment in routine clinical practice across 15 tertiary Headache Units in Spain.
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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.
Autres noms:
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.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Change from baseline in monthly headache days (MHD)
Délai: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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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.
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From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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Change from baseline in monthly migraine days (MMD).
Délai: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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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.
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From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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Proportion of patients achieving ≥30%, ≥50%, ≥75%, and 100% response rates over 12 months.
Délai: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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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.
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From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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Persistence of treatment response
Délai: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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Persistence of treatment response will be assessed as the proportion of patients who maintain their clinical response between Months 6 and 12.
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From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Characterization of sustained, late, and ultra-late treatment response
Délai: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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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.
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From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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Changes in migraine-related disability - HIT-6
Délai: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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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.
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From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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Changes in psychiatric comorbidities - HADS
Délai: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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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.
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From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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Changes in migraine-related comorbidities - ISI
Délai: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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Insomnia Severity Index (ISI) total score will be assessed at baseline and during follow-up in the subset of patients with available data.
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From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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Clinical predictors of sustained response at 12 months
Délai: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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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).
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From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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Impact of prior exposure to anti-CGRP monoclonal antibodies on treatment response
Délai: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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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).
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From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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Long-term safety of atogepant
Délai: From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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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).
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From baseline (initiation of atogepant treatment) to 12 months of follow-up.
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Collaborateurs et enquêteurs
Collaborateurs
Les enquêteurs
- Chercheur principal: Ana Belen Gago Veiga, Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
- Sécurité
- Migraine
- Mal de tête
- Tolérance
- Efficacité
- Surconsommation de médicaments
- Étude observationnelle
- Réponse au traitement
- Migraine chronique
- CGRP
- Sécurité à long terme
- Événements indésirables
- Étude prospective
- Long terme
- Résultats rapportés par les patients
- Résistance au traitement
- MMD
- Thérapie préventive
- HADS
- Monde réel
- Atogépant
- Prévention des migraines
- Peptide lié au gène de la calcitonine
- HIT-6
- Preuve du monde réel
- MHD
- Traitement préventif
- Étude du monde réel
- Gépant
- Gépants
- Migraine réfractaire
- anti-CGRP
- Resistant migraine
- Treatment-resistant migraine
- CGRP pathway
- Oral CGRP antagonist
- Preventive migraine therapy
- Mutlicentre study
- Long-term effectiveness
- Monthly headache days
- Monthly migraine days
- ISI
Termes MeSH pertinents supplémentaires
- Abus de drogues
- La douleur
- Manifestations neurologiques
- Maladies du cerveau
- Maladies du système nerveux central
- Maladies du système nerveux
- Les troubles mentaux
- Céphalées, primaires
- Troubles de la tête
- Troubles liés à une substance
- Troubles induits chimiquement
- Abus de médicaments sur ordonnance
- Conditions pathologiques, signes et symptômes
- Signes et symptômes
- Surconsommation de médicaments sur ordonnance
- Troubles migraineux
- Mal de tête
- Administration des services de santé
- Qualité des soins de santé, accès et évaluation
- Techniques d'investigation
- Méthodes épidémiologiques
- Collecte de données
- Mécanismes d'évaluation des soins de santé
- Qualité des soins de santé
- Santé publique
- Environnement et santé publique
- Économie et organisations des soins de santé
- Évaluation des résultats, soins de santé
- Évaluation des résultats et des processus, soins de santé
- Enquêtes et questionnaires
- Planification de la santé
- Enquêtes sur les soins de santé
- Recherche des services de santé
- Évaluation des résultats des patients
- atogepant
- Mesures des résultats signalés par les patients
Autres numéros d'identification d'étude
- 5600
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime IPD
Individual participant data (IPD) will not be shared with other researchers. This decision is based on data protection and confidentiality requirements in accordance with applicable European and national regulations (including GDPR). Given that this is a multicentre observational study conducted in routine clinical practice, access to IPD is restricted to the study investigators for the purposes of the predefined analyses.
Any potential secondary use of the dataset would only be considered in fully anonymized form and subject to prior ethical approval and compliance with applicable data protection legislation.
Informations sur les médicaments et les dispositifs, documents d'étude
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