Clinic 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 clinic and genetic factors associated with treatment failure is crucial for optimizing patients’ 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 <50% reduction in monthly migraine days. Results: Of 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 an association between the RAMP1 rs6431564 polymorphism and non-responder status, with the G allele linked to reduced risk (aOR per G allele: 0.28, p = 0.025) and causing increased expression of RAMP1 in an allele-dose manner. Conclusion: Hypertension, smoking, insomnia requiring medication and 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.