Clinical and Genetic Factors Associated with Non-Response to Erenumab

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.