Longitudinal assessment of migraine burden in resistant and refractory migraine – Data from the prospective REFINE study
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, d...
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2025-08-01
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| Series: | The Journal of Headache and Pain |
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| Online Access: | https://doi.org/10.1186/s10194-025-02126-9 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Umberto Pensato |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0116f5643f5e4339896807a09e849a68 |
| institution | DOAJ |
| issn | 1129-2377 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | The Journal of Headache and Pain |
| spelling | doaj-art-0116f5643f5e4339896807a09e849a682025-08-20T03:05:15ZengBMCThe Journal of Headache and Pain1129-23772025-08-0126111210.1186/s10194-025-02126-9Longitudinal assessment of migraine burden in resistant and refractory migraine – Data from the prospective REFINE studyUmberto Pensato0Raffaele Ornello1Chiara Rosignoli2Valeria Caponnetto3Agnese Onofri4Mark Braschinsky5Olga Sved6Raquel Gil-Gouveia7Renato Oliveira8Christian Lampl9Jakob Paungarttner10Paolo Martelletti11William David Wells-Gatnik12Isabel Pavao Martins13Dimos D. Mitsikostas14Loukia Apostolakopoulou15Aynur Ozge16Dilan Bayar Narin17Patricia Pozo-Rosich18Albert Munoz-Vendrell19Maria Pia Prudenzano20Martino Gentile21Kristina Ryliskiene22Jurgita VainauskieneMargarita Sanchez-del-Rio23Fabrizio Vernieri24Gianmarco Iaccarino25Marta Waliszewska-Prosół26Sławomir Budrewicz27Marta Carnovali28Zaza Katsarava29Simona Sacco30Department of Neurology, IRCCS Humanitas Research HospitalDepartment of Biotechnological and Applied Clinical Sciences, University of L’AquilaDepartment of Biotechnological and Applied Clinical Sciences, University of L’AquilaDepartment of Life, Health and Environmental Sciences, University of L’AquilaDepartment of Biotechnological and Applied Clinical Sciences, University of L’AquilaDepartment of Neurology and Neurosurgery, Institute of Clinical Medicine, Faculty of Medicine, University of Tartu and Neurology Clinic of Tartu University HospitalDepartment of Neurology and Neurosurgery, Institute of Clinical Medicine, Faculty of Medicine, University of Tartu and Neurology Clinic of Tartu University HospitalHeadache Center, Neurology Department, Hospital da LuzHeadache Center, Neurology Department, Hospital da LuzHeadache Medical Center, Seilerstaette LinzHeadache Medical Center, Seilerstaette LinzUnitelma Sapienza University of RomeTexas Tech University Health Sciences CenterCentro de Estudos Egas Moniz, Faculty of Medicine, University of LisbonFirst Department of Neurology, Aeginition Hospital, National and Kapodistrian University of AthensFirst Department of Neurology, Aeginition Hospital, National and Kapodistrian University of AthensDepartment of Neurology, NOROM Neuroscience and Neurotechnology Center of Excellence, Mersin University Medical FacultyDepartment of Neurology, NOROM Neuroscience and Neurotechnology Center of Excellence, Mersin University Medical FacultyHeadache Unit, Neurology Department, Headache and Neurological Pain Research Group, Vall d’Hebron University Hospital, VHIRHeadache Unit, Neurology Department, Headache and Neurological Pain Research Group, Vall d’Hebron University Hospital, VHIRHeadache Center, Neurological ClinicHeadache Center, Neurological ClinicCenter of Neurology, Vilnius UniversityDepartment of Neurology, Clínica Universidad de NavarraUnit of Headache and Neurosonology, Fondazione Policlinico Campus Bio- Medico and Neurology, Università Campus Bio-Medico di RomaUnit of Headache and Neurosonology, Fondazione Policlinico Campus Bio- Medico and Neurology, Università Campus Bio-Medico di RomaDepartment of Neurology, Wroclaw Medical UniversityDepartment of Neurology, Wroclaw Medical UniversityDepartment of Neurology, Christian Hospital Unna and University of Duisburg-EssenDepartment of Neurology, Christian Hospital Unna and University of Duisburg-EssenDepartment of Biotechnological and Applied Clinical Sciences, University of L’AquilaAbstract 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.https://doi.org/10.1186/s10194-025-02126-9HeadacheChronic migraineIntractableAnti-CGRPMonoclonal antibodiesGepants |
| spellingShingle | 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 Longitudinal assessment of migraine burden in resistant and refractory migraine – Data from the prospective REFINE study The Journal of Headache and Pain Headache Chronic migraine Intractable Anti-CGRP Monoclonal antibodies Gepants |
| title | Longitudinal assessment of migraine burden in resistant and refractory migraine – Data from the prospective REFINE study |
| title_full | Longitudinal assessment of migraine burden in resistant and refractory migraine – Data from the prospective REFINE study |
| title_fullStr | Longitudinal assessment of migraine burden in resistant and refractory migraine – Data from the prospective REFINE study |
| title_full_unstemmed | Longitudinal assessment of migraine burden in resistant and refractory migraine – Data from the prospective REFINE study |
| title_short | Longitudinal assessment of migraine burden in resistant and refractory migraine – Data from the prospective REFINE study |
| title_sort | longitudinal assessment of migraine burden in resistant and refractory migraine data from the prospective refine study |
| topic | Headache Chronic migraine Intractable Anti-CGRP Monoclonal antibodies Gepants |
| url | https://doi.org/10.1186/s10194-025-02126-9 |
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