Longitudinal assessment of migraine burden in resistant and refractory migraine – Data from the prospective REFINE study
Year: 2025
Type: article
Abstract: BACKGROUND: Some individuals with migraine fail to respond adequately to preventive treatments, bearing most of migraine burden. The European Headache Federation (EHF) classifies these individuals into resistant migraine (ResM) or refractory migraine (RefM) according to treatment failures, debilitating headache days, and disease duration. We investigated the evolution of these categories over six months in patients treated at tertiary headache centers and whether they accurately reflect disability and burden. METHODS: Participants from the multicenter, prospective REFINE study were classified into three categories of treatment responsiveness, namely RefM, ResM, and non-refractory non-resistant migraine (NRNRM). The primary objective was to determine the trajectories of category changes over six months. Secondary outcomes included changes in the 6-item Headache Impact Test (HIT-6), Headache-Attributed Lost Time (HALT), and Hospital Anxiety and Depression Scale (HADS-A and HADS-D) scores. RESULTS: Overall, 489 participants were included with a median age of 45 years (IQR = 36-53); 389 participants (79.7%) were female; 256 (52.4%) had NRNRM, 178 (36.4%) ResM, and 55 (11.2%) RefM. At follow-up, 200/256 (78.1%) NRNRM remained stable, while 56/256 (21.9%) progressed to ResM. Among those with ResM, 98/178 (55.1%) remained stable, 72/178 (40.5%) improved to NRNRM, and 8/178 (4.5%) worsened to RefM. Among participants with RefM, 37/55 (67.3%) remained stable, while 18/55 (32.7%) improved to NRNRM. Participants with RefM and ResM presented significantly higher scores at baseline than those with NRNRM. Over time, HIT-6, HALT, and HADS-A scores improved substantially in the overall cohort (p < 0.001, p < 0.001, and p = 0.006, respectively). Improvements were observed in participants with ResM across all scores and HIT-6 and HALT for NRNRM, but no improvement was noted in participants with RefM. CONCLUSIONS: Over six months, ~ 40% of ResM and ~ 30% of RefM individuals improved to NRNRM, while ~ 20% of NRNRM developed treatment resistance after receiving care in tertiary headache centers. Participants with ResM had a better prognosis than those with RefM. While both ResM and RefM reflect high migraine disability burden, they might present relevant differences in their management and prognosis.
Source: The Journal of Headache and Pain
Authors: Umberto Pensato, Raffaele Ornello, Chiara Rosignoli, Valeria Caponnetto, Agnese Onofri, Mark Braschinsky, Olga Sved, Raquel Gil-Gouveia, Renato Oliveira, Christian Lampl, Jakob Paungarttner, Paolo Martelletti, William David Wells-Gatnik, Isabel Pavao Martins, Dimos D. Mitsikostas, Loukia Apostolakopoulou, Aynur Ozge, Dilan Bayar Narin, Patricia Pozo-Rosich, Albert Munoz-Vendrell, Maria Pia Prudenzano, Martino Gentile, Kristina Ryliskiene, Jurgita Vainauskiene, Margarita Sanchez-del-Rio, Fabrizio Vernieri, Gianmarco Iaccarino, Marta Waliszewska-Prosół, Sławomir Budrewicz, Marta Carnovali, Zaza Katsarava, Simona Sacco
Institutions: Humanitas University, IRCCS Humanitas Research Hospital, University of L'Aquila, Tartu University Hospital, University of Tartu, Universidade Católica Portuguesa, Hospital da Luz, Unitelma Sapienza University, Sapienza University of Rome, Texas Tech University Health Sciences Center, University of Lisbon, National and Kapodistrian University of Athens, Eginition Hospital, Mersin Üniversitesi, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, University of Bari Aldo Moro, Vilnius University, Clinica Universidad de Navarra, Università Campus Bio-Medico, Campus Bio Medico University Hospital, Wroclaw Medical University, University of Duisburg-Essen
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,990
OpenAlex ID: W4413257238