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Background: Erenumab has demonstrated effectiveness for prevention of migraine attacks, but the treatment is costly, and a considerable proportion of patients do not respond to it. The Registry for Migraine study (REFORM) was initiated to discover biomarkers that can predict response to erenumab in patients with migraine. The specific objective was to investigate differences in erenumab efficacy based on clinical information, blood-based biomarkers, structural and functional magnetic resonance imaging (MRI), and response to intravenous infusion of calcitonin gene-related peptide (CGRP). In this first report of the REFORM study, we provide a comprehensive description of the study methodology, and present the baseline characteristics of the study population. Methods: The REFORM study was a single-center, prospective, longitudinal cohort study in adults with migraine who were scheduled to receive preventive treatment with erenumab as part of a separate, open-label, single-arm phase IV trial. The study included four periods: a 2-week screening period (Weeks -6 to -5), 4-week baseline period (Week -4 to Day 1), 24-week treatment period (Day 1 to Week 24), and a 24-week follow-up period without treatment (Week 25 to Week 48). Demographic and clinical characteristics were recorded using a semi-structured interview, whilst outcome data were obtained using a headache diary, patient-reported outcomes, blood sampling, brain MRI, and responsiveness to intravenous infusion of CGRP. Results: The study enrolled 751 participants, with a mean age ± SD of 43.8 ± 12.2 years, of which 88.8% (n = 667) were female. At enrollment, 64.7% (n = 486) were diagnosed with chronic migraine, and 30.2% (n = 227) had history of aura. The mean monthly migraine days (MMDs) was 14.5 ± 7.0. Concomitant preventive medications were used by 48.5% (n = 364) of the participants, and 39.9% (n = 300) had failed ≥ 4 preventive medications. Conclusion: The REFORM study enrolled a population with a high migraine burden and frequent use of concomitant medications. The baseline characteristics were representative of patients with migraine in specialized headache clinics. Future publications will report the results of the investigations presented in this article. Trial registration: The study and sub-studies were registered on ClinicalTrials.gov (NCT04592952; NCT04603976; and NCT04674020). [ABSTRACT FROM AUTHOR]

Abstract: Migraine is a common disabling disease with a complex pathophysiology. Headache is a frequent side effect after intravenous adenosine administration, although adenosine receptor antagonist, caffeine, relieves migraine headache. These observations suggest a possible involvement of adenosine signaling in headache and migraine pathophysiology. In a randomized, double-blinded, placebo-controlled, crossover study, 18 participants diagnosed with migraine without aura received 120 µg/kg per minute adenosine or placebo over 20 minutes. Headache intensity, migraine-associated symptoms, vital signs, the diameter of the superficial temporal artery (STA), blood flow velocity in the middle cerebral artery (V MCA ), and facial skin blood flow were measured at baseline and every 10 minutes until 2 hours after infusion start. The primary end point was the difference in the incidence of migraine attacks after adenosine infusion compared with placebo. Eighteen participants completed the study. We found no difference in the incidence of migraine after adenosine infusion (7 of 18, 39%) compared with placebo (3 of 18, 17%) ( P = 0.29). Fourteen participants reported headache after adenosine infusion (14 of 18, 78%) compared with placebo (6 of 18, 33%) ( P < 0.01). Adenosine increased heart rate ( P < 0.001), facial skin blood flow ( P < 0.05), and STA diameter (AUC T0-20min , P = 0.01) and decreased V MCA (AUC T0-20min , P < 0.001) compared with placebo. Adenosine induced headache accompanied by a short-lasting (<30 minutes) dilation of intracerebral and extracerebral arteries. The nonsignificant migraine induction might be because of the presence of several adenosine receptors with counteracting signaling, highlighting the need of more selective modulators to dissect the implication of adenosine in migraine. [ABSTRACT FROM AUTHOR]

Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article:Francesca Puledda declares speaker and consultancy fees from Abbvie and Teva. Simona Sacco declares grants/contracts, consulting fees or honoraria from Novartis, Uriach, Allergan-AbbVie, Teva, Lilly, Lundbeck, Pfizer, NovoNordisk, Abbott, AstraZeneca, Pfizer. Hans-Christoph Diener received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: AbbVie, Lilly, Lundbeck, Novartis, Pfizer, Teva and WebMD. The German Research Council (DFG) supports headache research by HCD. HCD serves on the editorial boards of Cephalalgia, Lancet Neurology and Drugs. Messoud Ashina is a consultant, speaker, or scientific advisor for AbbVie, Amgen, Astra Zeneca, Eli Lilly, GlaxoSmithKline, Lundbeck, Novartis, Pfizer, and Teva; a primary investigator for ongoing AbbVie and Pfizer trials; and is the past president of the International Headache Society. MA is supported through the Lundbeck Foundation Professor Grant (R310-2018-3711) and received institutional research grant from Lundbeck and Novartis. MA serves as associate editor of Journal of Headache Pain, and associate editor of Brain. Sait Ashina has received honoraria for consulting from Allergan/AbbVie, Eli Lilly, Impel NeuroPharma, Linpharma, Lundbeck, Pfizer, Satsuma, Teva, Theranica. SA is an associate editor for Neurology Reviews, BMC Neurology, and Frontiers in Neurology, and serves on the editorial board for Journal of Headache Pain. SA serves as a Trustee on the Board of the International Headache Society and is a member of the Education Committee of the International Headache Society. Eric Liebler declares consulting fees from ElecroCore, Inc. Andrea Cipriani is supported by the National Institute for Health Research (NIHR) Oxford Cognitive Health Clinical Research Facility, by an NIHR Research Professorship (grant RP-2017-08-ST2-006), by the NIHR Oxford and Thames Valley Applied Research Collaboration and by the NIHR Oxford Health Biomedical Research Centre (grant NIHR203316). The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health. Min Kyung Chu was a site investigator for a multicenter trial sponsored by Biohaven Pharmaceuticals, Allergan Korea, and Ildong Pharmaceutical Company. He received lecture honoraria from Eli Lilly and Company, Handok-Teva, and Ildong Pharmaceutical Company over the past 24 months. He received grants from Yonsei University College of Medicine (6-2021-0229), the Korea Health Industry Development Institute (KHIDI) (Grant No.: HV22C0106), and a National Research Foundation of Korea (NRF) grant. Alexandra Cocores declares grants/contracts from AbbVie, Eli Lilly, Rehaler. Esme Ekizoğlu declares honoraria from Allergan-AbbVie. David Garcia-Azorin declares grants/contracts from Carlos II Research and Castilla and Leon Regional Health, consulting fees from Eli-Lilly, WHO, Lundbeck or honoraria from AbbVie, Teva, Novartis, Pfizer. Carl Göbel declares honoraria from Fielmann AG and German Society for the Study of Pain. Maria Teresa Goicochea, personal fees as speaker or advisory board and/or non-financial support from Pfizer, AbbVie and Teva. Amr Hassan declares consulting fees or honoraria from Novartis, Sanofi Genzyme, Biologix, Merck, Hikma Pharma, Janssen, Inspire Pharma, Future Pharma, Elixir pharma, Allergan, Merck, Biologix, Roche, Bayer, Chemipharm, Al Andalus, and Clavita Pharm. Koichi Hirata declares consulting fees from Otsuka Pharma, and honoraria from Amgen Astellas BioPharma KK, Daiichi Sankyo, Eisai, Eli Lilly Japan KK, MSD, Otsuka Pharma, Pfizer Japan, and Sawai Pharma. Jan Hoffmann declares grants/contracts from Bristol Myers Squibb, International Headache Society (IHS), National Institute for Health and Care Research (NIHR), Medical Research Council (MRC) and Migraine Trust, consulting fees or honoraria from AbbVie, Cannovex, Eli Lilly, Novartis, Teva, Allergan, Chordate Medical AB, Lundbeck, Sanofi, MD Horizonte, Pfizer, Sage, NEJM Journal Watch Neurology, Oxford University Press, Quintessence Publishing, Springer Healthcare. He holds stock options from Chordate Medical AB. Bronwyn Jenkins declares honoraria from Allergan/AbbVie, Eli-Lilly, Novartis, Pfizer, Teva, Viatris. Katharina Kamm declares grants/contracts from the German Headache and Migraine Society, Novartis, consulting fees from Hormosan, and honoraria from Lundbeck, TEVA, derCampus, Novartis. Mi Ji Lee declares consulting fees or honoraria from Eli-Lilly, Lundbeck, Pfizer, NuEyne Co, Teva AbbVie, SK Chemical, CKD Pharma, and YuYu. Marco Lisicki declares honoraria from Teva, AbbVie, Novartis, Pfizer and Allergan. Daniele Martinelli declares honoraria from AbbVie and Lundbeck. Teshamae S. Monteith has the following disclosures over the past three years: clinical trial site principal investigator for studies sponsored by Abbvie, Eli Lilly, Ipsen and Rehaler, participation in advisory board/consultancy for AbbVie, Teva, Linpharma, e-Neura, Novartis, Merz, and Pfizer, Educational grant from Amgen and AbbVie, personal fees from Medscape, Massachusetts Medical Society, American Headache Society, American Academy of Neurology, Neurodiem, Academic CME, AbbVie, Novartis, unpaid co-author for research funded by AbbVie, Pfizer/Biohaven, and Theranica. She is an associate editor for Cephalalgia and Continuum Audio, and is on the editorial board for Neurology, American Migraine Foundation, and Brain and Life Magazine. Dr Monteith has provided unpaid service on the board of directors for the International Headache Society (2021-2023) and currently on the executive board for the Florida Society of Neurology. Raffaele Ornello declares grants/contracts from Novartis, consulting fees/honoraria from Eli Lilly, AbbVie, Pfizer, and Teva. Aynur Özge declares consulting fees or honoraria from AbbVie Lilly, Teva, Abdi Ibrahim, İlko and Drogsan. Mario Peres accepted honoraria for lectures, presentations, speakers’ bureaus, manuscript writing and educational events from Pfizer, Teva, AbbVie-Allergan, Lundbeck. Accepted travel support from Teva. Participated in advisory boards, AbbVie-Allergan, Eli Lilly, Pfizer, Kenvue, Eurofarma, Sanofi-Aventis. MP is president of ABRACES. Patricia Pozo-Rosich declares grants/contracts from ERANet Neuron, Instituto Salud Carlos III, Novartis, Teva and AbbVie and consulting fees or honoraria from AbbVie, Almirall, Eli Lilly, Lundbeck Medscape, Novartis, Pfizer, Teva. Todd J. Schwedt declares grants/contracts with American Heart Association, Amgen, Henry Jackson Foundation, National Headache Foundation, National Institutes of Health, Patient Centered Outcomes Research Institute, Pfizer, Spark Neuro, United States Department f Defense, American Migraine Foundation and Mayo Clinic. Consulting fees from AbbVie, Allergan, Amgen, Axsome, Biodelivery Science, Biohaven, Click Therapeutics, Collegium, Eli Lilly, Equinox, Ipsen, Unpharma, Lundbeck, Novartis, Satsuma, Scilex, Theranica, and Tonix. He declares royalties from UpToDate and stock options from Aural. Marcio Nattan P. Souza declares consulting fees or honoraria from Teva, Libbs, Pfizer, Sandoz, Lundbeck, Allergan/AbbVie, Lilly. Tsubasa Takizawa declares grants/research funds from Eli Lilly, Pfizer and Tsumura and advisory/consulting fees and/or honoraria from Eli Lilly, Daiichi Sankyo, Otsuka, Amgen, Teijin, Pfizer, Kyowa Kirin, Elsai, Kowa, UCB Japan, Takeda, and Santen Pharma. Gisela M. Terwindt declares grants/contracts from European Community, Dutch Heart Foundation, IRRF, Dioraphte and Dutch Brain Council with consulting fees or honoraria from Novartis, Lilly, Teva, AbbVie/Allergan, Lundbeck, Pfizer, Spring Media, Ashfield MedComms, Remedica Cygnea. Nicolas Vandenbussche declares consulting fees or honoraria Pfizer, AbbVie, Novartis, Teva, Babinski VZW, ACREHAB UGent. Shuu-Jiun Wang declares honoraria from AbbVie, Pfizer and Biogen. Cristina Tassorelli declares grants/contracts from AbbVie with consulting fees or honoraria from AbbVie, Eli Lilly, Dompé, Ipsen, Lundbeck, Pfizer, Medscape, Teva. All remaining authors report no disclosures or conflicts of interest

Background: In an effort to improve migraine management around the world, the International Headache Society (IHS) has here developed a list of practical recommendations for the acute pharmacological treatment of migraine. The recommendations are categorized into optimal and essential, in order to provide treatment options for all possible settings, including those with limited access to migraine medications., Methods: An IHS steering committee developed a list of clinical questions based on practical issues in the management of migraine. A selected group of international senior and junior headache experts developed the recommendations, following expert consensus and the review of available national and international headache guidelines and guidance documents. Following the initial search, a bibliography of twenty-one national and international guidelines was created and reviewed by the working group., Results: A total of seventeen questions addressing different aspects of acute migraine treatment have been outlined. For each of them we provide an optimal recommendation, to be used whenever possible, and an essential recommendation to be used when the optimal level cannot be attained., Conclusion: Adoption of these international recommendations will improve the quality of acute migraine treatment around the world, even where pharmacological options remain limited., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article:Francesca Puledda declares speaker and consultancy fees from TEVA.Simona Sacco declares grants/contracts, consulting fees or honoraria from Novartis, Uriach, Allergan-AbbVie, Teva, Lilly, Lundbeck, Pfizer, NovoNordisk, Abbott, AstraZeneca, Pfizer.Hans-Christoph Diener received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: AbbVie, Lilly, Lundbeck, Novartis, Pfizer, Teva and WebMD. The German Research Council (DFG) supports headache research by HCD. HCD serves on the editorial boards of Cephalalgia, Lancet Neurology and Drugs.Messoud Ashina is a consultant, speaker, or scientific advisor for AbbVie, Amgen, Astra Zeneca, Eli Lilly, GlaxoSmithKline, Lundbeck, Novartis, Pfizer, and Teva; a primary investigator for ongoing AbbVie and Pfizer trials; and is the past president of the International Headache Society. MA is supported through the Lundbeck Foundation Professor Grant (R310-2018-3711) and received institutional research grant from Lundbeck and Novartis. MA serves as associate editor of the Journal of Headache and Pain, and associate editor of Brain.Sait Ashina has received honoraria for consulting from Allergan/AbbVie, Eli Lilly, Impel NeuroPharma, Linpharma, Lundbeck, Pfizer, Satsuma, Teva, Theranica. SA is an Associate Editor for Neurology Reviews, BMC Neurology, and Frontiers in Neurology, and serves on the Editorial Board for the Journal of Headache and Pain. SA serves as a Trustee on the Board of the International Headache Society and is a member of the Education Committee of the International Headache Society.Eric Liebler declares consulting fees from ElecroCore, Inc.Andrea Cipriani is supported by the National Institute for Health Research (NIHR) Oxford Cognitive Health Clinical Research Facility, by an NIHR Research Professorship (grant RP-2017-08-ST2-006), by the NIHR Oxford and Thames Valley Applied Research Collaboration and by the NIHR Oxford Health Biomedical Research Centre (grant NIHR203316). The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health.Min Kyung Chu was a site investigator for a multicenter trial sponsored by Biohaven Pharmaceuticals, Allergan Korea, and Ildong Pharmaceutical Company. He received lecture honoraria from Eli Lilly and Company, Handok-Teva, and Ildong Pharmaceutical Company over the past 24 months. He received grants from Yonsei University College of Medicine (6-2021-0229), the Korea Health Industry Development Institute (KHIDI) (Grant No.: HV22C0106), and a National Research Foundation of Korea (NRF) grant.Alexandra Cocores declares grants/contracts from AbbVie, Eli Lilly, Rehaler.Esme Ekizoğlu declares honoraria from Allergan‐AbbVie.David Garcia-Azorin declares grants/contracts from Carlos II Research and Castilla and Leon Regional Health, consulting fees from Eli-Lilly, WHO, Lundbeck or honoraria from AbbVie, Teva, Novartis, Pfizer.Carl Göbel declares honoraria from Fielmann AG and German Society for the Study of Pain.Maria Teresa Goicochea, personal fees as speaker or advisory board and/or non-financial support from Pfizer, AbbVie and Teva.Amr Hassan declares consulting fees or honoraria from Novartis, Sanofi Genzyme, Biologix, Merck, Hikma Pharma, Janssen, Inspire Pharma, Future Pharma, Elixir pharma, Allergan, Merck, Biologix, Roche, Bayer, Chemipharm, Al Andalus, and Clavita pharm.Koichi Hirata declares consulting fees from Otsuka Pharma, and honoraria from Amgen Astellas BioPharma KK, Daiichi Sankyo, Eisai, Eli Lilly Japan KK, MSD, Otsuka Pharma, Pfizer Japan, and Sawai Pharma.Jan Hoffmann declares grants/contracts from Bristol Myers Squibb, IHS, National Institute of Health and Care Research (NIHR), Medical Research Council (MRC) and Migraine Trust, consulting fees or honoraria from AbbVie, Cannovex, Eli Lilly, Novartis, Teva, Allergan, Chordate Medical AB, Lundbeck, Sanofi, MD Horizonte, Pfizer, Sage, NEJM Journal Watch Neurology, Oxford University Press, Quintessence Publishing, Springer Healthcare. He holds stock options from Chordate Medical AB.Bronwyn Jenkins declares honoraria from Allergan/AbbVie, Eli-Lilly, Novartis, Pfizer, Teva, Viatris.Katharina Kamm declares grants/contracts from the German Headache and Migraine Society, Novartis, consulting fees from Hormosan, and honoraria from Lundbeck, TEVA, derCampus, Novartis.Mi Ji Lee declares onsulting fees or honoraria from Eli-Lilly, Lundbeck, Pfizer, NuEyne Co, Teva AbbVie, SK Chemical, CKD Pharma, and YuYu.Marco Lisicki declares honoraria from Teva, AbbVie, Novartis, Pfizer and Allergan.Daniele Martinelli declares honoraria from AbbVie and Lundbeck.Teshamae S. Monteith has the following disclosures over the past 3 years: clinical trial site principal investigator for studies sponsored by Eli Lilly and AbbVie (all paid to the institution), participation in an advisory board/consultancy for AbbVie, Teva, Linpharma, e-Neura, Novartis, Merz, and Pfizer, Educational grant from Amgen and AbbVie, personal fees from Medscape, Massachusetts Medical Society, American Headache Society, American Academy of Neurology, Neurodiem, Academic CME, AbbVie, Novartis, unpaid co-author for research funded by AbbVie, Pfizer/Biohaven, and Theranica. She is an associate editor for Cephalalgia and Continuum Audio, and is on the editorial board for Neurology, American Migraine Foundation, and Brain and Life Magazine. TSM has provided unpaid service on the board of directors for the International Headache Society (2021–2023) and currently on the executive board for the Florida Society of Neurology.Raffaele Ornello declares grants/contracts from Novartis, consulting fees/honoraria from Eli Lilly, AbbVie, Pfizer, and Teva.Aynur Ozge declares consulting fees or honoraria from AbbVie Lilly, Teva, Abdi Ibrahim, İlko and Drogsan.Mario Peres accepted honoraria for lectures, presentations, speakers bureaus, manuscript writing and educational events from Pfizer, Teva, AbbVie-Allergan, Lundbeck. Accepted travel support from Teva. Participated in advisory boards, AbbVie-Allergan, Eli Lilly, Pfizer, Kenvue, Eurofarma, Sanofi-Aventis. Mario Peres is president of ABRACES.Patricia Pozo-Rosich declares grants/contracts from ERANet Neuron, Instituto Salud Carlos III, Novartis, Teva and AbbVie and consulting fees or honoraria from AbbVie, Almirall, Eli Lilly, Lundbeck Medscape, Novartis, Pfizer, Teva.Todd J. Schwedt declares grants/contracts with AHA, Amgen, Henry Jackson Foundation, NIH, Patient Centered Outcomes Research Institute, Pfizer, Spark Neuro, US Dept. of Defense, AMF, NHF and Mayo Clinic with consulting fees from AbbVie, Allergan, Amgen, Axsome, Biodelivery Science, Biohaven, Click Therapeutics, Collegium, Eli Lilly, Equinox, Ipsen, Unpharma, Lundbeck, Novartis, Satsuma, Scilex, Theranica, and Tonix.Marcio Nattan P. Souza declares consulting fees or honoraria from Teva, Libbs, Pfizer, Sandoz, Lundbeck, Allergan/AbbVie, Lilly.Tsubasa Takizawa declares grants/research funds from Eli Lilly, Pfizer and Tsumura and advisory/consulting fees and/or honoraria from Eli Lilly, Daiichi Sankyo, Otsuka, Amgen, Teijin, Pfizer, Kyowa Kirin, Elsai, Kowa, UCB Japan, Takeda, and Santen Pharma.Gisela M. Terwindt declares grants/contracts from European Community, Dutch Heart Foundation, IRRF, Dioraphte and Dutch Brain Council with consulting fees or honoraria from Novartis, Lilly, Teva, AbbVie/Allergan, Lundbeck, Pfizer, Spring Media, Ashfield MedComms, Remedica Cygnea.Nicolas Vandenbussche declares consulting fees or honoraria Pfizer, AbbVie, Novartis, Teva, Babinski VZW, ACREHAB UGent.Shuu-Jiun Wang declares honoraria from AbbVie, Pfizer and Biogen.Cristina Tassorelli declares grants/contracts from AbbVie with consulting fees or honoraria from Eli Lilly, Dompé, Teva, Lundbeck, Pfizer, Medscape.All remaining authors report no disclosures or conflicts of interest.