{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T08:50:13Z","timestamp":1766134213528,"version":"3.48.0"},"reference-count":31,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Headache Centers"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, such as erenumab (ERE), are effective migraine-preventive therapies for many patients. Identifying clinical and genetic factors associated with treatment failure is crucial for optimizing patient management. Methods: This multicenter, prospective observational study included patients with episodic or chronic migraine treated with ERE for 12 months. Demographics, migraine history, comorbidities, treatment outcomes, and genetic variants in CGRP receptor-related genes (CALCRL and RAMP1) were evaluated for associations with non-response to ERE, defined as a &lt;50% reduction in monthly migraine days. Results: Of the 140 patients starting ERE, 11 were lost to follow up, 12 stopped ERE due to side effects; 18 patients were non-responders and were compared to 99 responders. Arterial hypertension [adjusted OR (aOR): 7.77, p = 0.007], smoking (aOR: 4.98, p = 0.014), and insomnia requiring medication (aOR: 4.51, p = 0.027) were associated with non-responder status. Genetic analysis revealed a nominal association between the RAMP1 rs6431564 polymorphism and non-responder status (nominal p = 0.025), which did not survive Bonferroni correction. The G allele was linked to a reduced risk (aOR per G allele: 0.28, p = 0.025) and caused the increased expression of RAMP1 in an allele-dose manner. Conclusions: Hypertension, smoking, insomnia requiring medication, and, nominally, the RAMP1 rs6431564 polymorphism were associated with non-responder status to ERE in migraine patients. Further validation of the present results in larger cohorts is needed.<\/jats:p>","DOI":"10.3390\/jcm14248922","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T13:42:52Z","timestamp":1765978972000},"page":"8922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and Genetic Factors Associated with Non-Response to Erenumab"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0031-9594","authenticated-orcid":false,"given":"Giulia","family":"Mallucci","sequence":"first","affiliation":[{"name":"Department of Neurology, Neurocenter of Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4909-1121","authenticated-orcid":false,"given":"Salvatore","family":"Terrazzino","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Giacon","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8002-7462","authenticated-orcid":false,"given":"Alberto","family":"Cordella","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neurocenter of Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6242-7817","authenticated-orcid":false,"given":"Sarah","family":"Cargnin","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4668-6098","authenticated-orcid":false,"given":"Christoph","family":"Schankin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Inselspital, Bern University Hospital, University of Bern, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7554-0664","authenticated-orcid":false,"given":"Claudio","family":"Gobbi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neurocenter of Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland"},{"name":"Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana, 6900 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9990-3431","authenticated-orcid":false,"given":"Chiara","family":"Zecca","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neurocenter of Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland"},{"name":"Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana, 6900 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1080\/17581869.2025.2509474","article-title":"Repurposed versus disease-specific medicinals for the prophylaxis of migraine: An updated systematic review","volume":"15","author":"Christofilos","year":"2025","journal-title":"Pain. 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