Clinical and Genetic Factors Associated with Non-Response to Erenumab

Area of Science:

• Neurology
• Pharmacogenomics

Background:

• Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, like erenumab (ERE), are established migraine preventive treatments.
• Identifying factors predicting treatment failure is essential for personalized migraine management.

Purpose of the Study:

• To investigate clinical and genetic predictors of non-response to erenumab (ERE) in patients with episodic or chronic migraine.
• To identify patient characteristics and genetic variants associated with suboptimal outcomes from ERE therapy.

Main Methods:

• A prospective observational study involving 140 migraine patients treated with ERE for 12 months.
• Evaluation of demographics, comorbidities, and genetic variants in CALCRL and RAMP1 genes.
• Non-response defined as <50% reduction in monthly migraine days.

Main Results:

• Hypertension (aOR: 7.77), smoking (aOR: 4.98), and insomnia requiring medication (aOR: 4.51) were significantly associated with ERE non-response.
• A nominal association was found between the RAMP1 rs6431564 polymorphism and non-response (nominal p=0.025).
• The G allele of RAMP1 rs6431564 was linked to reduced risk and increased RAMP1 expression.

Conclusions:

• Clinical factors including hypertension, smoking, and medication-treated insomnia predict erenumab non-response in migraine patients.
• The RAMP1 rs6431564 polymorphism warrants further investigation as a potential genetic marker for erenumab treatment outcomes.
• Larger cohort studies are necessary to validate these findings and refine patient selection for CGRP-targeted therapies.