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Volume 14
Issue 24
10.3390/jcm14248922
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Clinical and Genetic Factors Associated with Non-Response to Erenumab

by
Giulia Mallucci
1,†,
Salvatore Terrazzino
2,†,
Martina Giacon
2,
Alberto Cordella
1,
Sarah Cargnin
3,
Christoph Schankin
4,
Claudio Gobbi
1,5,‡ and
Chiara Zecca
1,5,*,‡
1
Department of Neurology, Neurocenter of Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland
2
Department of Pharmaceutical Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
3
Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
4
Department of Neurology, Inselspital, Bern University Hospital, University of Bern, 3012 Bern, Switzerland
5
Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6900 Lugano, Switzerland
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
These authors contributed equally to this work.
J. Clin. Med. 2025, 14(24), 8922; https://doi.org/10.3390/jcm14248922
Submission received: 14 November 2025 / Revised: 3 December 2025 / Accepted: 12 December 2025 / Published: 17 December 2025
(This article belongs to the Special Issue Advances and Updates in Migraine)
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Abstract

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 <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.
Keywords: anti CGRP antibodies; erenumab; migraine; treatment non-response anti CGRP antibodies; erenumab; migraine; treatment non-response
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MDPI and ACS Style

Mallucci, G.; Terrazzino, S.; Giacon, M.; Cordella, A.; Cargnin, S.; Schankin, C.; Gobbi, C.; Zecca, C. Clinical and Genetic Factors Associated with Non-Response to Erenumab. J. Clin. Med. 2025, 14, 8922. https://doi.org/10.3390/jcm14248922

AMA Style

Mallucci G, Terrazzino S, Giacon M, Cordella A, Cargnin S, Schankin C, Gobbi C, Zecca C. Clinical and Genetic Factors Associated with Non-Response to Erenumab. Journal of Clinical Medicine. 2025; 14(24):8922. https://doi.org/10.3390/jcm14248922

Chicago/Turabian Style

Mallucci, Giulia, Salvatore Terrazzino, Martina Giacon, Alberto Cordella, Sarah Cargnin, Christoph Schankin, Claudio Gobbi, and Chiara Zecca. 2025. "Clinical and Genetic Factors Associated with Non-Response to Erenumab" Journal of Clinical Medicine 14, no. 24: 8922. https://doi.org/10.3390/jcm14248922

APA Style

Mallucci, G., Terrazzino, S., Giacon, M., Cordella, A., Cargnin, S., Schankin, C., Gobbi, C., & Zecca, C. (2025). Clinical and Genetic Factors Associated with Non-Response to Erenumab. Journal of Clinical Medicine, 14(24), 8922. https://doi.org/10.3390/jcm14248922

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