Sacco et al. The Journal of Headache and Pain (2021) 22:39 https://doi.org/10.1186/s10194-021-01252-4 The Journal of Headache and Pain RESEARCH ARTICLE Open Access Burden and attitude to resistant and refractory migraine: a survey from the European Headache Federation with the endorsement of the European Migraine & Headache Alliance Simona Sacco1,2* , Christian Lampl3, Antoinette Maassen van den Brink4, Valeria Caponnetto1,2, Mark Braschinsky5, Anne Ducros6, Patrick Little7, Patricia Pozo-Rosich8,9, Uwe Reuter10, Elena Ruiz de la Torre7, Margarita Sanchez Del Rio11, Alexandra J. Sinclair12,13, Paolo Martelletti14,15, Zaza Katsarava16,17,18,19 and On behalf of the Burden and Attitude to Resistant and Refractory (BARR) Study Group Abstract Background: New treatments are currently offering new opportunities and challenges in clinical management and research in the migraine field. There is the need of homogenous criteria to identify candidates for treatment escalation as well as of reliable criteria to identify refractoriness to treatment. To overcome those issues, the European Headache Federation (EHF) issued a Consensus document to propose criteria to approach difficult-to- treat migraine patients in a standardized way. The Consensus proposed well-defined criteria for resistant migraine (i.e., patients who do not respond to some treatment but who have residual therapeutic opportunities) and refractory migraine (i.e., patients who still have debilitating migraine despite maximal treatment efforts). The aim of this study was to better understand the perceived impact of resistant and refractory migraine and the attitude of physicians involved in migraine care toward those conditions. Methods: We conducted a web-questionnaire-based cross-sectional international study involving physicians with interest in headache care. (Continued on next page) * Correspondence: simona.sacco@univaq.it 1 Neuroscience section – Department of Biotechnological and Applied Clinical Sciences and (Edificio Coppito 2), University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy 2 Regional Referral Headache Center of the Abruzzo Region, ASL Avezzano-Sulmona-L’Aquila, L’Aquila, Italy Full list of author information is available at the end of the article © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Sacco et al. The Journal of Headache and Pain (2021) 22:39 Page 2 of 10 (Continued from previous page) Results: There were 277 questionnaires available for analysis. A relevant proportion of participants reported that patients with resistant and refractory migraine were frequently seen in their clinical practice (49.5% for resistant and 28.9% for refractory migraine); percentages were higher when considering only those working in specialized headache centers (75% and 46% respectively). However, many physicians reported low or moderate confidence in managing resistant (8.1% and 43.3%, respectively) and refractory (20.7% and 48.4%, respectively) migraine patients; confidence in treating resistant and refractory migraine patients was different according to the level of care and to the number of patients visited per week. Patients with resistant and refractory migraine were infrequently referred to more specialized centers (12% and 19%, respectively); also in this case, figures were different according to the level of care. Conclusions: This report highlights the clinical relevance of difficult-to-treat migraine and the presence of unmet needs in this field. There is the need of more evidence regarding the management of those patients and clear guidance referring to the organization of care and available opportunities. Keywords: Migraine, Resistant migraine, Refractory migraine, Migraine care Background Methods New migraine treatments, both acute and preventa- Study design, setting, and participants tive, such as lasmiditan, monoclonal antibodies We conducted a web-questionnaire-based cross- (mAbs) targeting the calcitonin gene-related peptide sectional international study involving headache physi- (CGRP) pathway, and gepants are changing the land- cians. All physicians involved in the care of patients with scape of migraine treatment offering new opportun- headache, without any restriction referring to country of ities and challenges [1–5]. Those treatments raised residency, specialization, and years of experience in the issue of appropriate selection of patients because headache care were entitled to fill the questionnaire. their direct cost is higher than the conventional medi- The e-questionnaire was shared at the 2020 annual cations [6]. Additionally, despite having a high re- EHF virtual conference and by advertisement on social sponder rate, a proportion of patients still do not media. Additionally, the questionnaire was publicized by respond according to conventionally accepted defini- mailing lists and national websites by the national head- tions [7–10]. A recent real-life observational study ache societies affiliated to the EHF. Sharing was started found that 38% of patients who failed all available in July 2020 and the data base was locked on 03 October preventatives were non-responders after 6 months of 2020. treatment to one CGRP targeting monoclonal anti- body (erenumab) [11]. Instruments and data collection In order to move forward in the field of difficult-to- The e-questionnaire was developed by discussion and treat migraine patients, the European Headache Feder- consensus within the study panel (Supplement 1). The ation (EHF) with the endorsement of the European Mi- questionnaire was built online using Redcap®, a software graine & Headache Alliance (EMHA) issued a for designing research databases [13]. Consensus document to propose criteria to approach Before starting to fill-out the questionnaire partici- those patients [12]. In details, the new definitions of the pants were provided with a figure summarizing the defi- difficult to treat migraine included non-response to nitions of resistant and refractory migraine and with the acute and preventative medications. So, two diagnostic link to the published Consensus article [12]. categories were identified, i.e., resistant and refractory Each participant had to report gender, specialization, migraine. First, 8 days with debilitating migraine despite years of experience in headache medicine, the work set- intake acute antimigraine medication was defined as the ting and the number of patients visited per week. threshold. Further, patients who tried three different Work settings categories were defined, according to classes of migraine preventative and still suffer eight de- EHF definitions of the level of care [14], as follows: 1) bilitating migraine days classify for resistant migraine. In first level of care - General primary care defined as first- order to be defined as refractory, failure to all available line headache service (accessible first contact for most classes of migraine preventatives, including mAbs target- people with headache); 2) second level of care - Special- ing the CGRP pathway, is required. interest headache care defined as ambulatory care deliv- Therefore, the aim of this study was to better under- ered by physicians with a special interest in headache; 3) stand the clinical reality and the attitude of physicians third level of care - Headache Specialists Centers defined involved in migraine care toward these patients. as advanced multidisciplinary care delivered by headache Sacco et al. The Journal of Headache and Pain (2021) 22:39 Page 3 of 10 Fig. 1 Distribution by country of participating physicians specialists in hospital-based centers. These definitions incomplete. Distribution by country is reported in [14] were also provided as a part of the e-questionnaire. Fig. 1. Characteristics of participants according to years of practice in headache medicine, specialty, Data protection, sharing, and ethics and work setting are reported in Table 1. The questionnaire was not anonymous, and participants Resistant migraine was frequently encountered in were requested to provide consent to be listed as con- clinical practice. Overall, 137/277 (49.5%) partici- tributors to the study. Guarantee was provided referring pants reported that they manage very frequently to the use of the provided information only in aggre- patients with resistant migraine, 100 (36.1%) partici- gated forms and not at an individual level. Group pants reported that they manage occasionally those authorship was granted to all those completing the ques- patients, and 40 (14.4%) reported that they manage tionnaire (Burden and Attitude to Resistant and Refrac- rarely those patients. Those percentages were tory [BARR] Study Group). As the study did not involve use data from single pa- Table 1 Characteristics of the participants who completed the tients, we did not ask for an Ethic Committee approval. survey The data base of this study is stored at the University of Characteristics n % L’Aquila and is available upon reasonable request form Females 133 48.0 authorities and researchers by contacting the corre- sponding author. Years in headache medicine after graduation ≤ 5 years 73 26.4 Statistical analyses 6–10 years 54 19.5 We used descriptive statistics and provided distributions > 10 150 54.2 of the responses to selected questions. Chi-squared test Specialty was performed to compare frequencies among variables Neurology 250 90.3 of interest. The level of significance was set at P < 0.05. All statistical analyses were performed with SPSS Other 27 9.7 Statistics 21.0. Work setting General primary care/general neurology 83 30.0 Results Special interest headache care 71 25.6 The present paper is based on questionnaires filled Headache specialist center 123 44.4 by 277 physicians (n = 133; 48.0% female); 15 ques- Academic center 131 47.3 tionnaires were discarded because they were Sacco et al. The Journal of Headache and Pain (2021) 22:39 Page 4 of 10 significantly different among the three possible levels 46% of physicians reported that they manage very fre- of care (P < 0.0001). In fact, in headache specialist quently patients with refractory migraine the corre- centers, 75% of physicians reported that they manage sponding proportion was 23% for special interest very frequently patients with resistant migraine; the headache care and 8% for general primary care/neur- corresponding proportion was 48% for special inter- ology (Fig. 2). est headache care and 13% for general primary care/ Overall, 22 (8.1%) respondents reported low, 117 neurology (Fig. 2). (43.3%) moderate, and 131 (48.5%) high confidence in Refractory migraine was as well a condition fre- treating resistant migraine, while 57 (20.7%) reported quently encountered in clinical practice. Overall, 80/ low, 133 (48.4%) moderate, and 85 (30.9%) high confi- 277 (28.9%) participants reported that they manage dence in treating refractory migraine As shown in Fig. 3, very frequently patients with refractory migraine, 110 confidence in treating patients with resistant and refrac- (39.7%) reported that they manage occasionally those tory migraine was different according to the level of care patients, and 86 (31.0%) reported that they manage (P < 0.001 and P = 0.006, respectively), to the number of rarely those patients. These percentages were signifi- migraine patients visited per week (P < 0.001 for both), cantly different among the different levels of care to the years in headache medicine after graduation of (P < 0.0001). In fact, in headache specialist centers, the treating physician (P < 0.001 for both), and to the Fig. 2 Response to the question “How often do you see in your practice patients with resistant/refractory migraine?” Sacco et al. The Journal of Headache and Pain (2021) 22:39 Page 5 of 10 Fig. 3 Low, moderate or high confidence in managing resistant and refractory migraine according to characteristics of headache care and physicians frequency of resistant/refractory migraine patients vis- referred to a more specialized center. The corresponding ited (P < 0.001 for both). data were 224 (80.9%) and 52 (18.8%) respectively for re- Overall, 245/277 (88.4%) respondents reported that pa- fractory migraine. Figures were significantly different ac- tients with resistant migraine were treated in their own cording to the level of care (P < 0.001 for both resistant center, while 32 (11.6%) reported that patients were and refractory), as reported in Fig. 4. Sacco et al. The Journal of Headache and Pain (2021) 22:39 Page 6 of 10 Fig. 4 Response to the question “Where are patients with resistant/refractory treated?” Referring to the ideal setting of care, 22 (6%) respon- practice and in research settings, to select homogenous dents considered that resistant migraine should be man- populations of migraine patients who require treatment aged in general primary care, 162 (43%) in special escalation. This would ensure a more standardized clin- interest headache care, and 191 (51%) in specialized ical management of patients and research results’ com- headache centers. The corresponding figures for refrac- parability. Second, while in the past mostly passive tory migraine were 19 (6%), 95 (28%) and 230 (67%) re- acceptance of the lack of successful treatment for some spectively (Fig. 5). patients with migraine was registered, nowadays re- searchers are looking for novel migraine specific thera- Discussion peutic targets. The study of patients who do not have As new treatment opportunities are entering the mi- adequate response to the available migraine treatments graine filed, new challenges are faced by those who are may provide not only more therapeutic opportunities, involved in migraine care and research [15–17]. First, but also may improve our understanding in the mecha- there is the need of reliable criteria, both in clinical nisms underlying migraine in general. Sacco et al. The Journal of Headache and Pain (2021) 22:39 Page 7 of 10 Fig. 5 Response to the question “Where should patients with resistant/refractory migraine be managed?” The present study reports a summary of the impact more years in practice) reported more often a high con- and attitude toward resistant and refractory migraine. fidence in treating both resistant and refractory mi- Our data showed that both resistant and refractory mi- graine, further highlighting the lack of standardized graine are commonly and globally faced in the headache guidelines and the consequent physicians’ trend to care. Resistant and refractory migraine are particularly mainly rely on their expertise. common in tertiary level headache centers, where 75% Surprisingly, we found a low referral to more advanced and 46%, respectively, of the physicians use to see very levels of care for patients with resistant and refractory frequently those patients. However, despite being rela- migraine, despite a relevant proportion of physicians op- tively common, many physicians reported a sub-optimal erating in the two more basic levels of care expressed confidence in managing those patients. Remarkably, from low to moderate confidence in treating those pa- even in tertiary level headache centers, only 39% of phy- tients. On the other hand, around half of the participants sicians reported high confidence in managing patients considered that tertiary level headache care is the ideal with refractory migraine. The figure may be attributed setting for resistant migraine and 2/3 of participants by lack of knowledge of the definition, lack of additional considered that tertiary level headache care is the ideal treatment possibilities and lack of guidelines which may setting for refractory migraine. help to support those patients. However, physicians with This preliminary report provides a gross understand- more experience (i.e., more patients visited per week and ing of resistant and refractory migraine, however with Sacco et al. The Journal of Headache and Pain (2021) 22:39 Page 8 of 10 some limitations. Responses were based on perceptions Burden and Attitude to Resistant and Refractory (BARR) Study Group: and opinions of the participants and bias and inaccuracy. Albania: Genci Cakciri, Pavllo Djamandi, Serla Grabova, Gleni Halili, Jera Kruja, Altin Kuqo, Diana Naco, Aida Quka, Ladjola Stefanidhi, Gentian Vyshka, Ilirjana Additionally, generalizability of the findings can be lim- Zekja. Argentina: Osvaldo Bruera, Dilver Gómez, Brenda Guitian, Juan Carlos ited. In fact, there were many countries (among them Roma. Australia: Ike Leon Chen. Austria: Christian Lampl. Azerbaijan: Samira United States and Canada) with lack of responders; the Bashirova. Belarus: Maxim Linkov. Belgium: Daan Van Den Abbeele, Geraldine Vanderschueren. Brasil: Roberta Araujo, Renato Arruda, Antônio distribution of responders was not homogenous across Catharino, Jovana Ciriaco, Amauri Dalla Corte, Ricardo Dornas, Bernardo countries. Due to the limited number of participants per Felsenfeld Jr., André Fonseca Taufner, Yara Fragoso, Rubens Hurtado, Daniel country, we could not perform country-specific analyses. Isoni Martins, Renata Londero, Luciano Melo, Kelton Stivenson Mignoni, Paulo Victor Sgobbi De Souza, Marcio Nattan Souza. Bulgaria: Sevdzhan Additionally, also availability of new migraine drugs and Osman. Chile: Veronika Baltzer. Colombia: Luis Fabian Pacheco Mosquera. the system of care are variable across countries, and this Croatia: Ivan Dubroja, Zlatko Hucika, Marijana Lisak, Arijana Lovrencic-Huzjan, may reflect different attitudes which were not examined Ivo Lušić, Darija Mahovic Lakusic. Czech Republic: Petr Mikulenka, Pavel Řehulka. Denmark: Faisal Mohammad Amin, Sonja Antic, Zainab Fakhril-Din, by our study. An upcoming filed testing and real-life Jakob Moeller-Hansen, Signe Munksgaard, Ana Maria Nan, Lanfranco Pellesi, prospective international study in headache centers Henrik Schytz. El Salvador: Manuel Vides. Estonia: Kati Braschinsky, Mark across Europe (A real-life study on Resistant and rEFrac- Braschinsky, Ülle Krikmann. France: Anne Ducros, Caroline Roos, Alexandre Cauchie, Lucas Christian, Evelyne Guégan-Massardier, Genevieve Demarquay, tory migraINE [REFINE]) will provide more insights on Geraud Gilles, Jerome Mawet, Emmanuelle Kuhn, Michel Lanteri Minet, the validity of the proposed definitions as well as on the Mihaela Bustuchina Vlaicu, Xavier Moisset, Mirela Muresan, Mitra Najjar-Ravan, characteristics and clinical course of patients who meet Pierric Giraud, Sabine Simonin, Solène De Gaalon. Georgia: George Chakhava, Miranda Demuria, George Gegelashvili, Nana Kapanadze. Germany: Angela the definition criteria for resistant and refractory Antonakakis, Charly Gaul, Stefanie Förderreuther, Jana-Isabel Huhn, Sardor migraine. Ibragimov, Katharina Kamm, Bianca Raffaelli, Reiner Czaniera, Ruth Rusche- weyh, Uwe Reuter. Greece: Evangelia Gavanozi, Georgios Karagiorgis, Theo- doros Mavridis. Hungary: Csaba Ertsey. India: Dubey Shubham. Indonesia: Conclusions Antonia Dewi Callista Tanowi, Stefanus Erdana Putra, Deby Wahyuning Hadi, Resistant and refractory migraine are conditions Leny Kurnia, Musadir Nasrul. Italy: Maria Albanese, Fabio Antonaci, Gian Maria which are perceived as common in the clinical prac- Asioli, Roberta Baschi, Enrico Bentivegna, Nicoletta Brunelli, Salvatore Caratoz- zolo, Teresa Catarci, Alessandra Cherchi, Ilenia Corbelli, Alfredo Costa, Ciro De tice of those involved in the care of patients with Luca, Alberto Doretti, Valentina Favoni, Natascia Ghiotto, Maria Adele Giam- migraine and working in dedicated headache care or berardino, Luca Giani, Giorgio Zanchin, Flora Govone, Giovanni Grillo, centers. Despite being common, there is a lot of un- Edoardo Mampreso, Paolo Martelletti, Andrea Negro, Raffaele Ornello, Mar- cello Pasculli, Umberto Pensato, Maria Pia Addolorata Prudenzano, Simone certainty from physicians, pointing out the need of Quintana, Rosaria Rapisarda, Michele Romoli, Antonio Russo, Marco Russo, support. It would be important to set up organized Simona Sacco, Valerio Spuntarelli, Cindy Tiseo, Angelo Torrente, Alessandro systems for referral of the difficult-to-treat patients Vacca, Giovanna Vaula, Alessandro Viganò, Simone Vigneri. Latvia: Aija Frei- mane, Evita Slosberga, Linda Zvaune. Malaysia: Hui Jan Tan. Malta: Cherilyn from general primary care/neurology and eventually Fenech. Mexico: Rafael Cobilt-Catana, Yazmín De La Garza Neme, Marco Mar- from special interest headache care to tertiary head- tínez, Jefferson Voltaire Proaño Narvaez, Andrea Rodriguez Herrera, Damaris ache centers and to provide guidance on migraine Vazquez. Moldova: Oxana Grosu. North Macedonia: Adi Jakupi. Norway: Espen Saxhaug Kristoffersen, Erling Tronvik, Bendik S. Winsvold. Pakistan: care in situations where the positive clinical response Mehboob Azhar. Perù: Maria Teresa Reyes Alvarez, Leidi Vilchez Fernandez. if difficult to achieve. Further research is also needed Philippines: Greg David Dayrit. Poland: Ewa Katarzyna Czapinska-Ciepiela, to clarify the mechanisms which contribute to drug Michal Fila, Anna Gryglas-Dworak. Portugal: Marina Couto, Paula Esperança, Axel Ferreira, Raquel Gil-Gouveia, Ana Goncalves, Margarida Lopes, Miguel refractoriness in migraine, to understand the role of Lourenço, Jorge Machado, Manuel Marinho, Miguel Angelo Miranda, Filipe comorbidities and the therapeutic opportunities aris- Palavra, Elsa Parreira, Isabel Pavao Martins, Liliana Pereira, José Maria Pereira ing from combination drugs. Moreover, underlying Monteiro. Republic of Moldova: Pavel Leahu. Romania: Stefan Aloman. Rus- sian Federation: Ekaterina Abramova, Leila Akhmadeeva, Anastasia Belopa- mechanisms in migraine are far from being entirely sova, Inna Bogdanova, Mariya Chernyak, Miss Epifanova, Elena Fedorova, clear and there hope that the ongoing future re- Anton Felbush, Maria Karpova, Daria Korobkova, Daria Korotkova, Nina Laty- search may shade light on novel targets which may sheva, Tatiana Makeeva, Kristina Mikhalkina, Vera Osipova, Olga Roshchina, Anna Serga, O.V. Serousova, Yulia Sidorova, Iaroslav Skiba, Kirill Skoroboga- allow the development of new drugs. tykh, Nina Vashchenko. Serbia: Slobodan Apostolski, Nevenka Buder, Aleksan- dar Kopitovic, Jovanovic Mirjana, Ana Podgorac, Dejan Rakic, Svetlana Simić, Abbreviations Martinovic Zarko, Jasna Zidverc Trajkovic. Spain: Isabel Beltran-Blasco, María EHF: European Headache Federation; EMHA: European Migraine & Headache Dolores Calabria Gallego, Samuel Díaz Insa, David Ezpeleta, María Fernández, Alliance; CGRP: Calcitonin gene-related peptide; mAbs: Monoclonal David García-Azorín, Nuria González-García, Angel L. Guerrero, Edelmira Guil- antibodies lamon, Jaime Herreros Rodriguez, Almudena Layos-Romero, Vicente Medrano, Ane Mínguez-Olaondo, Santiago Navarro Muñoz, Martí Paré Curell, Patricia Pozo-Rosich, Marta Ruibal, Jose Maria Sanchez Alvarez, Margarita San- Supplementary Information chez Del Rio, Sonia Santos, Rafael Soler, Javier Viguera, Ramon Zabalza. The online version contains supplementary material available at https://doi. Sudan: Tagwa Abdelrahman, Salih Boushra Abobaker Hamza, Mohammed org/10.1186/s10194-021-01252-4. Nasir Mustafa. Sweden: Lars Edvinsson. Switzerland: Andreas Gantenbein, Isa- bella Maraffi. The Netherlands: Emile Couturier, Thijs Dirkx, Michel Hoebert, Additional file 1. EHF survey on resistant/refractory migraine. Wpj Van Oosterhout, Mulleners Wim, Rachel Zwartbol. Turkey: Mesut Bakır, Hatice Demirel, Ali Kemal Erdemoglu, Devrimsel H. Ertem, Sinan Gönüllü, Elif Ilgaz Aydinlar, Levent Ertuğrul Inan, Berkay Ölmez, Taner Ozbenli, Aynur Özge, Acknowledgements Derya Uluduz, Tugba Uyar Cankay, Pinar Yalinay Dikmen. United Arab Not applicable. Sacco et al. The Journal of Headache and Pain (2021) 22:39 Page 9 of 10 Emirates: Amrit Bhushan Saxena. Ukraine: Myroslav Bozhenko, Nataliya Boz- Margarita Sanchez Del Rio: Fees as speaker or for participation to advisory henko, Rostyslav Bubnov, Olena Tsurkalenko. United Kingdom: Ishaq Abu- boards from Allergan, Eli-Lilly, Novartis, Teva. Arafeh, Luis Idrovo, Sarah Miller, Niranjanan Nirmalananthan, Alexandra Sin- Alexandra J Sinclair: Fees as speaker from Novartis and Allergan. clair, Esteban Taleti, Alex Valori, William Whitehouse, Adam Zermansky. West Valeria Caponnetto: Fees as member of Advisory Board from Novartis. Midlands: Myat Thura. Author details Authors’ contributions 1 Neuroscience section – Department of Biotechnological and Applied SS and ZK conceived this study and drafted the first version of the Clinical Sciences and (Edificio Coppito 2), University of L’Aquila, Via Vetoio, questionnaire and of the paper; VC managed the data base and performed 67100 L’Aquila, Italy. 2Regional Referral Headache Center of the Abruzzo statistical analysis; MB, AD, CL, PM, AMVDB, PPR, UR, MSDR, AJ S contributed Region, ASL Avezzano-Sulmona-L’Aquila, L’Aquila, Italy. 3Department of to develop the questionnaire revised the paper for important intellectual Neurology, Headache Medical Centre Linz, Hospital Barmherzige Brüder, content; PL and ERDLT revised the paper for important intellectual content. Centre of Integrative Medicine (ZiAM) Ordensklinikum Linz, Linz, Austria. 4 All authors have approved the submitted version. Division of Pharmacology, Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. 5 Headache Clinic, Department of Neurology, Tartu University Clinics, Tartu, Authors’ information Estonia. 6Headache Unit, Neurology Department, Montpellier University European Headache Federation (EHF) Council: ZK (president), CL (1st vice- Hospital and Montpellier University, Montpellier, France. 7European Migraine president), AMVDB (2nd vice-president), SS (treasurer), PM (past-president), & Headache Alliance (EMHA), Brussels, Belgium. 8Headache Unit, Neurology MB (member), PPR (member), UR (member), MSDR (member), AS (member), Department, Vall d’Hebron University Hospital, Barcelona, Spain. 9Headache AD (member). and Neurological Pain Research Group, Department de Medicina, Universitat European Migraine & Headache Alliance (EMHA): PL (president), ERDLT Autònoma de Barcelona, Vall d’Hebron Research Institute, Barcelona, Spain. (Executive Director, Company Secretary and Immediate Past President). 10 Charité Universitätsmedizin Berlin, Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany. 11Neurology Department, Clinica Funding Universidad de Navarra, Madrid, Spain. 12Metabolic Neurology, Institute of Publication fees for this publication were covered by the European Metabolism and Systems Research, College of Medical and Dental Sciences, Headache Federation. University of Birmingham, Birmingham, UK. 13Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK. 14 Availability of data and materials Department of Clinical and Molecular Medicine, Sapienza University of Not applicable. Rome, Rome, Italy. 15Regional Referral Headache Center of the Lazio Region, Sant’Andrea Hospital, Rome, Italy. 16Christian Hospital, Unna, Germany. 17 Declarations Department of Neurology, University of Duisburg-Essen, Essen, Germany. 18 EVEX Medical Corporation, Tbilisi, Georgia. 19IM Sechenov First Moscow Ethics approval and consent to participate State Medical University (Sechenov University), Moscow, Russian Federation. Not applicable. Received: 10 March 2021 Accepted: 3 May 2021 Consent for publication Not applicable. References Competing interests 1. De Matteis E, Guglielmetti M, Ornello R, Spuntarelli V, Martelletti P, Sacco S Mark Braschinsky: Fees as a speaker or for participation to advisory boards (2020) Targeting CGRP for migraine treatment: mechanisms, antibodies, from Abbott Laboratories, Allergan Inc., Berlin-Chemie AG (Menarini Group), small molecules, perspectives. 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J Headache Pain 20(1):49. https://doi.org/10.1186/s101 Allergan, Eli-Lilly, Novartis, Teva. 94-019-1000-5 Antoinette Massen van den Brink: Research grant and/or speaker/consultant 6. Sacco S, Bendtsen L, Ashina M, Reuter U, Terwindt G, Mitsikostas DD, fees from Amgen/Novartis, Eli-Lilly, Teva. Martelletti P (2019) European headache federation guideline on the use of Patricia Pozo-Rosich: Fees as consultant and speaker for Allergan, Almirall, monoclonal antibodies acting on the calcitonin gene related peptide or its Biohaven, Chiesi, The Corpus, Eli Lilly, Medscape, Neurodiem, Novartis and receptor for migraine prevention. J Headache Pain 20(1):6. https://doi.org/1 Teva. Research funding from, AGAUR, ERANet Neuron, FEDER RISC3CAT, la 0.1186/s10194-018-0955-y Caixa foundation, Instituto Investigación Carlos III, MICINN, Migraine Research 7. 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