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Original research
Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world
  1. Edoardo Caronna1,2,
  2. Victor José Gallardo2,
  3. Gabriella Egeo3,
  4. Manuel Millán Vázquez4,
  5. Candela Nieves Castellanos5,
  6. Javier A Membrilla6,7,
  7. Gloria Vaghi8,9,
  8. Joana Rodríguez-Montolio10,11,
  9. Neus Fabregat Fabra12,
  10. Francisco Sánchez-Caballero13,
  11. Alex Jaimes Sánchez14,
  12. Albert Muñoz-Vendrell15,
  13. Renato Oliveira16,
  14. Gabriel Gárate17,
  15. Yésica González-Osorio18,
  16. Daniel Guisado-Alonso19,
  17. Raffaele Ornello20,
  18. Cem Thunstedt21,
  19. Iris Fernández-Lázaro22,
  20. Marta Torres-Ferrús1,2,
  21. Alicia Alpuente1,2,
  22. Paola Torelli23,
  23. Cinzia Aurilia3,
  24. Raquel Lamas Pére4,
  25. Maria José Ruiz Castrillo6,
  26. Roberto De Icco8,9,
  27. Grazia Sances9,
  28. Sarah Broadhurst24,
  29. Hui Ching Ong24,
  30. Andrea Gómez García14,
  31. Sergio Campoy15,25,
  32. Jordi Sanahuja26,
  33. Gonçalo Cabral27,
  34. Isabel Beltrán Blasco28,
  35. Marta Waliszewska-Prosół29,
  36. Liliana Pereira30,
  37. Almudena Layos-Romero31,
  38. Isabel Luzeiro32,33,
  39. Laura Dorado34,
  40. María Rocio Álvarez Escudero35,
  41. Arne May36,
  42. Alba López-Bravo11,37,
  43. Isabel Pavão Martins38,
  44. Christina Sundal39,40,41,42,
  45. Pablo Irimia43,
  46. Alberto Lozano Ros44,
  47. Ana Beatriz Gago-Veiga22,
  48. Fernando Velasco Juanes45,
  49. Ruth Ruscheweyh21,
  50. Simona Sacco20,
  51. Elisa Cuadrado-Godia19,46,
  52. David García-Azorín18,
  53. Julio Pascual17,
  54. Raquel Gil-Gouveia16,47,
  55. Mariano Huerta-Villanueva15,25,
  56. Jaime Rodriguez-Vico14,
  57. Javier Viguera Romero13,
  58. Victor Obach12,
  59. Sonia Santos-Lasaosa10,11,
  60. Mona Ghadiri-Sani24,
  61. Cristina Tassorelli8,9,
  62. Javier Díaz-de-Terán6,7,
  63. Samuel Díaz Insa5,
  64. Carmen González Oria4,
  65. Piero Barbanti3,48,
  66. Patricia Pozo-Rosich1,2
  67. For the EUREkA study group
    1. 1Headache Clinic, Neurology Department, Vall d'Hebron Hospital, Barcelona, Spain
    2. 2Headache and Neurological Pain Research Group, Vall d'Hebron Research Institute, Barcelona, Spain
    3. 3Headache and Pain Unit, IRCCS San Raffaele, Roma, Italy, Italian Migraine Registry (IGRAINE) study group
    4. 4Unidad de Cefaleas, Hospital Universitario Virgen del Rocío, Sevilla, Spain
    5. 5Headache Unit, Department of Neurology, Hospital Universitari i Politècnic La Fe, Valencia, Spain
    6. 6Headache Unit, Department of Neurology, La Paz University Hospital, Madrid, Spain
    7. 7La Paz Institute for Health Research (IdiPAZ), Autonomous University of Madrid, Madrid, Spain
    8. 8Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
    9. 9Headache Science & Neurorehabilitation Center, IRCCS Mondino Foundation, Pavia, Italy
    10. 10Department of Neurology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
    11. 11Aragon Institute for Health Research (IIS Aragón), Zaragoza, Spain
    12. 12Neurology Department Headache Unit, Hospital Clinic, Barcelona, Spain
    13. 13Headache Unit, Hospital Virgen Macarena, Seville, Spain
    14. 14Headache Unit, Hospital Universitario Fundación Jiménez Díaz Madrid, Madrid, Spain
    15. 15Headache Unit, Neurology Department, Hospital Universitari de Bellvitge-IDIBELL, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
    16. 16Hospital da Luz Headache Center, Neurology Department, Hospital da Luz, Lisboa, Portugal
    17. 17Neurology Department, University Hospital Marqués de Valdecilla, Universidad de Cantabria, Santander, Spain
    18. 18Headache Unit, Department of Neurology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
    19. 19Department of Neurology, Hospital del Mar, Barcelona, Spain
    20. 20Department of Applied Clinical Sciences and Biotechnology, University of L'Aquila, L'Aquila, Italy
    21. 21Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany
    22. 22Headache Unit, Department of Neurology, Hospital Universitario La Princesa, Madrid, Spain
    23. 23Neurology Unit, Department of Medicine and Surgery, Headache Center, University of Parma, Parma, Italy, Italian Migraine Registry (IGRAINE) study group
    24. 24The Walton Centre NHS Foundation Trust, Liverpool, UK
    25. 25Neurology Department, Hospital de Viladecans-IDIBELL, Viladecans, Barcelona, Spain
    26. 26Headache Unit, Department of Neurology, Hospital Universitari Arnau de Vilanova-IRBLleida, Lleida, Spain
    27. 27Neurology Department, Hospital de Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal
    28. 28Headache Clinic, Neurology Departament, Hospital General Universitario Dr Balmis, ISABIAL, Alicante, Spain
    29. 29Department of Neurology, Wrocław Medical University, Wrocław, Poland
    30. 30Department of Neurology, Hospital Garcia de Orta, Almada, Portugal
    31. 31Headache Unit, Neurology Department, Hospital General Universitario de Albacete, Albacete, Spain
    32. 32Headache Outpatient Unit, Hospitalar and University Centre of Coimbra, Coimbra, Portugal
    33. 33Coimbra Health School/ESTeSC, Coimbra, Portugal
    34. 34Department of Neuroscience, Germans Trias i Pujol University Hospital, Badalona, Spain
    35. 35Headache Unit, Department of Neurology, University Hospital Central de Asturias, Oviedo, Spain
    36. 36University Clinic Hamburg, Hamburg, Germany
    37. 37Headache Unit, Department of Neurology, Hospital Reina Sofía, Tudela, Spain
    38. 38Headache Outpatient Clinic, Neurology Department, Hospital Universitario Sta Maria, Faculty of Medicine University of Lisbon & Campus Neurologico, Lisbon, Portugal
    39. 39Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway
    40. 40NorHEAD, Norwegian Headache Research Centre, Oslo, Norway
    41. 41Department of Neurology, NeuroClinic, Norway, Lillestrøm, Norway
    42. 42Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy University of Gothenburg, Gothenburg, Sweden
    43. 43Department of Neurology, Clinica Universidad de Navarra, Pamplona, Spain
    44. 44Headache Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
    45. 45Department of Neurology, Hospital Universitario Cruces, Biocruces Bizkaia Health Research Institute, Bilbao, Spain
    46. 46Neuroscience Research Program, Hospital del Mar Research Institute, Pompeu Fabra University, Barcelona, Spain
    47. 47Center for Interdisciplinary Research in Health, Universidade Católica Portuguesa, Lisboa, Portugal
    48. 48University San Raffaele, Rome, Italy
    1. Correspondence to Dr Patricia Pozo-Rosich, Neurology Department, Vall d’Hebron Hospital, Barcelona, Spain; patricia.pozo{at}vallhebron.cat

    Abstract

    Background Anti-CGRP monoclonal antibodies (anti-CGRP MAbs) are approved and available treatments for migraine prevention. Patients do not respond alike and many countries have reimbursement policies, which hinder treatments to those who might respond. This study aimed to investigate clinical factors associated with good and excellent response to anti-CGRP MAbs at 6 months.

    Methods European multicentre, prospective, real-world study, including high-frequency episodic or chronic migraine (CM) patients treated since March 2018 with anti-CGRP MAbs. We defined good and excellent responses as ≥50% and ≥75% reduction in monthly headache days (MHD) at 6 months, respectively. Generalised mixed-effect regression models (GLMMs) were used to identify variables independently associated with treatment response.

    Results Of the 5818 included patients, 82.3% were females and the median age was 48.0 (40.0–55.0) years. At baseline, the median of MHD was 20.0 (14.0–28.0) days/months and 72.2% had a diagnosis of CM. At 6 months (n=4963), 56.5% (2804/4963) were good responders and 26.7% (1324/4963) were excellent responders. In the GLMM model, older age (1.08 (95% CI 1.02 to 1.15), p=0.016), the presence of unilateral pain (1.39 (95% CI 1.21 to 1.60), p<0.001), the absence of depression (0.840 (95% CI 0.731 to 0.966), p=0.014), less monthly migraine days (0.923 (95% CI 0.862 to 0.989), p=0.023) and lower Migraine Disability Assessment at baseline (0.874 (95% CI 0.819 to 0.932), p<0.001) were predictors of good response (AUC of 0.648 (95% CI 0.616 to 0.680)). These variables were also significant predictors of excellent response (AUC of 0.691 (95% CI 0.651 to 0.731)). Sex was not significant in the GLMM models.

    Conclusions This is the largest real-world study of migraine patients treated with anti-CGRP MAbs. It provides evidence that higher migraine frequency and greater disability at baseline reduce the likelihood of responding to anti-CGRP MAbs, informing physicians and policy-makers on the need for an earlier treatment in order to offer the best chance of treatment success.

    • migraine
    • health policy & practice

    Data availability statement

    Data are available on reasonable request. All data are available and any anonymised data will be shared on reasonable request from any qualified investigator.

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    Data availability statement

    Data are available on reasonable request. All data are available and any anonymised data will be shared on reasonable request from any qualified investigator.

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    Footnotes

    • Collaborators European real-world study on the Use of anti-CGRP monoclonal antibodiEs in migrAine (EUREkA) study group: Daniel Guisado-Alonso, PhD, Neurology Department, Hospital del Mar, Barcelona, Spain; Neuroscience Research Program, Hospital del Mar Research Institute. Pompeu Fabra University, Barcelona, Spain. Raffaele Ornello, PhD, Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy. Cem Thunstedt, MD, Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany. Iris Fernández-Lázaro, MSc, Headache Unit. Neurology Department. Hospital Universitario La Princesa. Antonio Sánchez-Soblechero, MD, Headache Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain. Andreas Husoy, PhD, Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway; NorHEAD, Norwegian Headache Research Centre, Oslo, Norway. Beatriz Nunes Vicente, MD, Headache Outpatient Clinic, Neurology Department, Hospital Universitario Sta Maria, Lisbon, Portugal. Hauke Basedau, University Clinic Hamburg, Hamburg, Germany. Nuria Pilar Riesco Pérez, PhD, Headache Unit, Department of Neurology, University Hospital Central de Asturias, Oviedo, Spain. Belen Flores Pina, MD, Department of Neuroscience, Germans Trias i Pujol University Hospital, Badalona, Spain. Catarina Fernandes, MD, Headache Outpatient Unit, Hospitalar and University Centre of Coimbra, Coimbra, Portugal. Alberto Andrés-López, MD, Headache Unit, Neurology Department, Hospital General Universitario de Albacete, Albacete, Spain. Elisa Martins-Silva, MD, Department of Neurology, Hospital Garcia de Orta, Almada, Portugal. Sławomir Budrewicz, PhD, Department of Neurology, Hospital Garcia de Orta, Almada, Portugal. Pablo Ros Arlanzón, MD, Headache Clinic, Neurology Departament, Hospital General Universitario Dr Balmis, ISABIAL, Alicante, Spain. André Caetano, PhD, Neurology Department, Hospital de Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal. Silvana Zapata, MD, Neurology Department, Universidad de Antioquia, Antioquia, Colombia. Sonsoles Aranceta, Neurology Department, Hospital Parc Tauli, Spain. Izaro Kortazar Zubizarreta, MD, Neurology Department, Hospital Universitario de Alava, Alava, Spain. Amalia Echeverria Urabayen, MD, Neurology Department, Hospital Universitario de Alava, Alava, Spain. Inês Marques, MD, Hospital da Luz Headache Center, Neurology Department, Hospital da Luz, Lisboa, Portugal. Elsa Parreira, MD, Hospital da Luz Headache Center, Neurology Department, Hospital da Luz, Lisboa, Portugal. Vicente González-Quintanilla, PhD, Neurology Department, University Hospital Marqués de Valdecilla, Universidad de Cantabria, Santander, Spain. Ángel Luis Guerrero-Peral, PhD, Headache Unit, Department of Neurology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain; Department of Medicine, University of Valladolid, Valladolid, Spain. Isabel Miró, MD, Department of Neurology, Hospital del Mar, Barcelona, Spain. Julia Peris-Subiza, MD, Department of Neurology, Hospital del Mar, Barcelona, Spain. Valeria Caponnetto, MSN, PhD, Department of Applied Clinical Sciences and Biotechnology, University of L'Aquila, L'Aquila, Italy. Andreas Straube, MD, Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany. Alicia Gonzalez-Martinez, PhD, Headache Unit, Department of Neurology, Hospital Universitario La Princesa, Madrid, Spain. Sonia Quintas, MD, Headache Unit, Department of Neurology, Hospital Universitario La Princesa, Madrid, Spain. Margarita Sánchez-del-Río, MD, Headache Unit, Neurology Department, Clínica Universidad de Navarra, Madrid, Spain. Erling Tronvik, PhD, Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway. NorHEAD, Norwegian Headache Research Centre, Oslo, Norway. Begoña Venegas Pérez, MD, Headache Unit, Department of Neurology, University Hospital Central de Asturias, Oviedo, Spain. Agustin Oterino Durán, PhD, Headache Unit, Department of Neurology, University Hospital Central de Asturias, Oviedo, Spain. Miguel Rodrigues, MD, Department of Neurology, Hospital Garcia de Orta, Almada, Portugal. Ana Fries Ramos, MD, Headache Clinic, Neurology Departament, Hospital General Universitario Dr Balmis, ISABIAL, Alicante, Spain. Yago Vaamonde Esteban, MD, Headache Clinic, Neurology Departament, Hospital General Universitario Dr Balmis, ISABIAL, Alicante, Spain. Sabina Cevoli, MD, PhD, Headache Center IRCCS Istituto delle Scienze Neurologiche Bologna, Italy; Italian Migraine Registry (IGRAINE) study group. Bruno Colombo, MD, Headache Unit Scientific Institute San Raffaele Hospital, Vita-Salute University, Milan, Italy; Italian Migraine Registry (IGRAINE) study group. Michele Trimboli, MD, Headache Centre, Department of Neurology, AOR "San Carlo", Potenza, Italy; Italian Migraine Registry (IGRAINE) study group. Fabio Frediani, MD, Headache Center, ASST Santi Paolo Carlo, Milan, Italy; Italian Migraine Registry (IGRAINE) study group. Florindo d’Onofrio, MD, Hedache Center, San Giuseppe Moscati Hospital, Avellino, Italy; Italian Migraine Registry (IGRAINE) study group. Marco Aguggia, MD, Headache Center Cardinal Massaia Hospital, Asti, Italy; Italian Migraine Registry (IGRAINE) study group. Antonio Salerno, MD, Headache Center, S Giovanni Addolorata Hospital, Rome, Italy; Italian Migraine Registry (IGRAINE) study group. Antonio Carnevale, MD, Headache Center, Ospedale San Filippo Neri - ASL Roma 1, Rome, Italy; Italian Migraine Registry (IGRAINE) study group. Maurizio Zucco, MD, Headache Center, Neurology Unit, San Camillo-Forlanini Hospital, Rome; Italian Migraine Registry (IGRAINE) study group. Maria Albanese, MD, PhD, Headache Center, University Hospital Tor Vergata, Rome, Italy; Italian Migraine Registry (IGRAINE) study group. Cinzia Finocchi, MD, Neurology Unit, San Paolo Hospital, ASL 2 Savona, Italy; Italian Migraine Registry (IGRAINE) study group. Angelo Ranieri, MD, Headache Center, AORN A. Cardarelli, Napoli, Italy; Italian Migraine Registry (IGRAINE) study group. Francesco Zoroddu, MD, Pediatric Headache Center, Neurology Unit, University of Sassari, Italy; Italian Migraine Registry (IGRAINE) study group. Massimo Autunno, MD, Headache Center, Department of Clinical and Experimental Medicine, University of Messina, Italy; Italian Migraine Registry (IGRAINE) study group.

    • Contributors PP-R and EC made substantial contributions to conception and study design. All authors worked for acquisition of data. EC and VJG contributed to data analysis. All authors contributed to the interpretation of data. EC and VJG wrote the first draft. All authors critically revised and finally approved the version to be published. All authors fully comply with and approve the version to be published. PPR acted as the guarantor.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare: EC has received honoraria from Novartis, Chiesi, Lundbeck, MedScape; his salary has been partially funded by Río Hortega grant Acción Estratégica en Salud 2017–2020, Instituto de Salud Carlos III (CM20/00217). He is a junior editor for Cephalalgia. GE received travel grants and honoraria from Eli-Lilly, Novartis, Lusofarmaco, New Penta and Ecupharma. CNC has received honoraria for advisories, educational or commercial symposia from: Abbvie-Allergan, Kern Pharma, Chiesi, Lilly, Lundbeck, Novartis and Teva Pharmaceuticals And has participated as subinvestigator in Clinical Trials for: Abbvie-Allergan, Amgen, Biohaven, Lilly, Lundbeck, Pfizer and Teva Pharmaceuticals. JAM has received honoraria as consultant and/or speaker for Lilly, Novartis, Teva. FS-C received honoraria from Novartis, Lilly, TEVA, Abbvie. AM has received honoraria from Teva, Lilly, Roche, UCB, Bial, Chiesi, Allergan, Esai, Zambon, Kern Pharma, Pfizer, Biogen Idec, Novartis, TEVA, Merck, Janssen, Neuraxpharm, Genzyme, Sanofi, Bayer, Almirall and/or Celgene. JS received honoraria from Allergan, Lilly, Teva, Novartis. IBB received honoraria for presentations from Novartis, Lilly, Teva, Lundbeck and Abbvie. MW-P received honoraria from Pfizer, Allergan-Abbvie, TEVA, Polpharma. MW-P is member of Editorial Board: The Journal of Headache and Pain. LP received honoraria from Pfizer, Lilly, Abbvie, TEVA, Novartis. AL-R received honoraria for Abbvie, Lilly, Novartis and Teva. IL received honoraria from Novartis, Abbvie, Teva, Eisai, Tecnifar and Bial. LD received honoraria as a speaker for Allergan, Lilly, Teva and Lundbeck. MRA-E, received honoraria from ABBVIE, Lilly, and Novartis. AM has no COI to declare. The University Clinic Hamburg got an unrestricted scientific grant from Novartis (2019-2023). IPM has received honoraria from Allergan Teva, Novartis, Lundbeck and Eli Lilly for lecturing or participating in advisory boards; is principal investigator for phase IV trials sponsored by Novartis, Lundbeck and Teva. CS has received personal fees for lectures/ advisory boards: Novartis, Abbvie and TEVA. PI received honoraria from TEVA, Novartis, Lilly, Abbvie, Lundbeck, Exeltis. ALR received honoraria from TEVA. ABG-V has received speaker honoraria and/or clinical advisor from Novartis, Lilly, TEVA, Exeltis, Chiesi, Abbvie, Pfizer and Lundbeck. RR has received travel grants and/or honoraria for lectures or advisory boards from Allergan/AbbVie, Hormosan, Lilly, Lundbeck, Novartis, Pfizer and Teva. SS reports consultant, speaker or advisory board fees from Abbott, Allergan/Abbvie, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Eli Lilly, Medscape, Medtronic, Novartis, Pfizer, Starmed, Teva and Uriach. EC-G received honoraria from TEVA. DGA has received personal compensation for consulting/advising from the WHO. Non-profit board membership in the Spanish Society of Neurology, and the European Union of Medical Specialist section of Neurology. Research funding from the Regional Health Administration (Gerencia Regional de Salud SACYL) in Castilla y Leon, Spain and Carlos III institute, Madrid, Spain. Speaker/travel grants/ clinical trials from Teva, Allergan, Amgen, Eli Lilly, Lundbeck, Novartis and Biohaven. JP has received honoraria from Abbvie, Lilly, Lundbeck, Novartis and Teva. RG-G received honoraria from Allergan/ Abbvie, Lilly, Lundbeck, Novartis, Pfizer, Tecnifar, Teva. MH-V has received honoraria for participating on advisory boards and for collaborations as consultant, scientific communications, speaker, research support as well as funding for travel and congress-attending expenses for Abbie-Allergan, Novartis, Lundbeck, Lilly, Almirall, Chiesi, Esai, Exeltis, Kern Pharma, Menarini, TEVA and Zambon. His research group has received research grants from Abbie-Allergan and has received funding for clinical trials from Lilly, Novartis, TEVA. JVR received honoraria from Novartis, Abbvie, Lilly, TEVA, Lundbeck. SS-L received honoraria from Allergan, Almirall, Amgen, Chiesi, Eisai, Exeltis, Lilly, Lündbeck, Novartis, Pfizer y Teva. MG-S has received honoraria and been involved in research, education and advisory boards with Teva, Lily, Novartis and Abbvie. CT received personal fees for participating in advisory or for speaking at scientific events from AbbVie, Allergan, Biohaven, Dompé, Eli Lilly, Lundbeck, Novartis and Teva. CT has received research funding from the European Commission, the Italian Ministry of Health and Migraine Research Foundation. JDdT has received honoraria as consultant and/or speaker for Lilly, Novartis, Teva. SDI has received honoraria for advisories, educational or commercial symposia from: Abbvie-Allergan, Fundació Universitat-Empresa, Ipsen Pharma, Kern Pharma, Lilly, Lundbeck, MSD-Organon, Novartis and Teva Pharmaceuticals And has participated as PI in Clinical Trials for: Abbvie-Allergan, Alder, Amgen, Biohaven, Ipsen Pharma, Lilly, Lundbeck, Pfizer and Teva Pharmaceuticals. CGO participated in clinical trials from Novartis, St Jude Medical, Lilly, Lundbeck; TEVA, Biohaven, Pfizer. CGO received honoraria as consultant for Novartis, Lilly, Allergan-abbvie, Lundbeck, TEVA, Pfizer. CGO received honoraria as speaker for Allergan-Abbvie, TEVA, Novartis,Lilly, Chiesi, MSD, Almirall. PB reports personal compensation for consulting, serving on a scientific advisory board, speaking, research support, collaborated for clinical trials or other activities with Abbvie, Alder, Allergan, Amgen, Angelini, Assosalute, Bayer, Biohaven, ElectroCore, Eli-Lilly, Fondazione Ricerca e Salute, GSK, Lundbeck, Lusofarmaco, 1MED, MSD, New Penta, Noema Pharma, Novartis, Pfizer, Stx-Med, Teva, Visufarma, Zambon and serves as President with Italian Association of Headache Sufferers. PP-R has received, in the last 3 years, honoraria as a consultant and speaker for: AbbVie, Biohaven, Chiesi, Eli Lilly, Lundbeck, Medscape, Novartis, Pfizer and Teva. Her research group has received research grants from AbbVie, Novartis and Teva; as well as, Instituto Salud Carlos III, EraNet Neuron, European Regional Development Fund (001-P-001682) under the framework of the FEDER Operative Programme for Catalunya 2014-2020 - RIS3CAT; has received funding for clinical trials from AbbVie, Amgen, Biohaven, Eli Lilly, Novartis, Teva. She is the Honorary Secretary of the International Headache Society. She is in the editorial board of Revista de Neurologia. She is an associate editor for Cephalalgia, Headache, Neurologia, The Journal of Headache and Pain and Frontiers of Neurology. She is a member of the Clinical Trials Guidelines Committee of the International Headache Society. She has edited the Guidelines for the Diagnosis and Treatment of Headache of the Spanish Neurological Society. She is the founder of www.midolordecabeza.org. PP-R does not own stocks from any pharmaceutical company. VJG, MMV, GV, JR-M, NFF, AJS, RO, GG, YG-O, GC, AL-B, FVJ, JR-V and VO reports no disclosures. RO reports personal fees from Eli Lilly, Novartis, Teva, and Pfizer, and non-financial support from Novartis, Teva, and Allergan/AbbVie. CT has received honoraria for lectures from TEVA, Lundbeck and for advisory boards from TEVA. He has received travel support from TEVA and Lundbeck. SS received honoraria from TEVA. AH declares no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. HB received honoraria from Novartis, Teva and Lundbeck. NPRP received honoraria from ABBVIE, Lilly and Novartis. CF received honoraria from Novartis and Abbvie. AAL received honoraria for Abbvie, Lilly, Novartis and Teva. EMS received a grant from the Portuguese Headache Society, supported by Teva. MTF has received honoraria from Allergan-AbbVie, Novartis, Chiesi and Teva. AA has received honoraria from Allergan-AbbVie, Novartis, Chiesi. PT received grants and honoria from Novartis, Teva, Eli-Lilly and Allergan. CA received travel grants from FB-Health, Lusofarmaco, Almirall, Eli-Lilly Novartis and Teva. RDI received speaker honoraria from Eli-Lilly, TEVA and Lundbeck. GS received personal fees as speaker or advisory board from Eli Lilly, Novartis, Teva, Lundbeck, Pfizer. SB has received honoraria from Teva. SC has received honoraria from Teva, Lilly, Roche, UCB, Bial, Chiesi, Allergan, Esai, Zambon, Kern Pharma, Pfizer, Biogen Idec, Novartis, TEVA, Merck, Janssen, Neuraxpharm, Genzyme, Sanofi, Bayer, Almirall and/or Celgene. EP reports personal fees from Novartis, Teva and Lilly. ALGP Research funding from the Regional Health Administration (Gerencia Regional de Salud SACYL) in Castilla y Leon, Spain. Speaker/travel grants/ clinical trials from Teva, Allergan, Amgen, Eli Lilly, Lundbeck, Novartis, Pfizer and Biohaven. AS has received honoraria for advisory boards and lectures from Allergan/AbbVie, Hormosan, Lilly, Lundbeck, Novartis, Sanofi, Teva. AGM has received speaker honoraria from TEVA. SQ has received speaker honoraria from Novartis, Lilly and Exeltis. MSR has received consulting fees and honoraria for lectures/presentations from Eli Lily, Lundbeck, Novartis, Teva and Pfizer. Intellectual as Secretary of the European Headache Federation, Review Editor on the Editorial Board of Headache and Neurogenic Pain (specialty section of Frontiers in Neurology). Margarita Sanchez-del-Rio serves as a member of the Board of Directors in the European Headache Federation. ET has received personal fees for lectures/ advisory boards: Novartis, Eli Lilly, Abbvie, TEVA, Roche, Lundbeck, Pfizer, Biogen. Consultant for and owner of stocks and IP in Man & Science. Stocks and IP in Nordic Brain Tech and Keimon Medical. Non-personal research grants from EU, Norwegian Research Council, Dam foundation, KlinBeForsk. Commissioned research (non-personal): Lundbeck, Pfizer. BVP received honoraria from ABBVIE. AOD received honoraria from ABBVIE, Lilly, Teva, Novartis. MR received honoraria from Lilly, Novartis. BC received grants and honoria from Eli-Lilly, Novartis, Teva; SC received travel grants, honoraria for advisory boards, speaker panels or clinical investigation studies from Novartis, Teva, Lilly, Allergan, Abvie, Ibsa, Amgen, Angelini and Lundbeck; FF has received fees for participation on advisory boards, speaker honoraria or consulting activities from Angelini, Cristalfarma, Ecupharma, IBSA, Lundbeck, Novartis, PIAM, Teva; FdO received travel grant, honoraria as a speaker or for partecipating in advisory boards from Novartis, Teva, Neopharmed Gentili, Qbgroup srl, K link srl and Eli-Lilly; MA received grants from Novartis and Lilly; RR received honoraria for speaker panels from Teva, Lilly, Novartis, Allergan, Lundbeck; MZ received travel grants and honoraria from Novartis; MA received travel grants and honoraria from Novartis, Teva, Eli-Lilly and Lundbeck; CF received grants and honoraria from Novartis, Eli Lilly, TEVA, AIM group; AR received travel grants and honoraria from Teva and Eli-Lilly; SZ, RLP, MJRC, VGQ, HCO, SA, IKZ, DGA, IFL, BFP, SB, PRA, AC, AEU, AGG, IM, JPS, VC, AFR, YVE, MT, AS, AC, FZ and MA has no disclosures to declare.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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