The Registry for Migraine (REFORM) study: methodology, demographics, and baseline clinical characteristics

Abstract

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).

Association of atopic dermatitis and headache disorder: a systematic review and meta-analyses

“…To our knowledge, this is the first meta-analysis to assess the association between AD and headache disorder. The fairly frequent coexistence of migraine and allergic diseases was well described in previous epidemiologic studies ( 30 , 31 ). While recent meta-analyses ( 11 – 13 ) have indicated a bidirectional association between asthma and headache disorder, our study extends this understanding.…”

Postdromal symptoms in migraine: a REFORM study

“…The present investigation is part of the larger parental Registry for Migraine (REFORM) study and was carried out at a single tertiary care unit [ 11 ]. The study protocol received approval from the relevant ethics committee and data protection agency.…”

“…All participants provided written informed consent before any study-related tasks or procedures were performed. A detailed description of the methods used in the parental study can be found elsewhere [ 11 ].…”

Premonitory symptoms in migraine: A REFORM Study

“…REFORM is a prospective, single-center study that included participants from a single-arm, open-label, phase IV trial (NCT04265755) at the Danish Headache Center (5). The detailed methodology of REFORM is reported elsewhere (14).…”

“…Three PROMs were used as secondary measures: Migraine Disability Assessment (MIDAS) (21), Headache Impact Test (HIT-6) (22) and a shortened version of the World Health Organization Disability Assessment 2.0 (WHODAS 2.0) (23). MIDAS scores (the sum of missed days per three months because of headache) were categorized as "little or no disability" (0-5), "mild disability" (6-10), "moderate disability" (11)(12)(13)(14)(15)(16)(17)(18)(19)(20) or "severe disability" (!21) (21). HIT-6 scores in the range 36-78 were categorized as "little or no impact" ( 49), "some impact" (50-59), "substantial impact" (56-59) or "severe impact" (60-78) (22).…”