Response to erenumab assessed by Headache Impact Test‐6 is modulated by genetic factors and arterial hypertension: An explorative cohort study.

Background and purpose: Response predictors to erenumab (ERE) in migraine patients would benefit their clinical management. We investigate associations between patients' clinical characteristics and polymorphisms at calcitonin receptor‐like receptor (CALCRL) and receptor activity‐modifying protein 1 (RAMP1) genes and response to ERE treatment measured as clinically meaningful improvement on the Headache Impact Test‐6 (HIT‐6) score. Methods: This post hoc analysis of a prospective, multicenter, investigator‐initiated study involves 110 migraine patients starting ERE 70 mg/month. Demographics, medical history, and migraine‐related burden measured by HIT‐6 score were collected during 3 months before and after ERE start. Selected polymorphic variants of CALCRL and RAMP1 genes were determined using real‐time polymerase chain reaction. Logistic regression models identified independent predictors for response to ERE, defined as HIT‐6 score improvement ≥ 8 points (HIT‐6 responders [HIT‐6 RESP] vs. HIT‐6 nonresponders). Results: At Month 3, 58 (52.7%) patients were HIT‐6 RESP. Comorbid hypertension predicted a lower probability of being HIT‐6 RESP (odds ratio [OR] = 0.160, 95% confidence interval [CI] = 0.047–0.548, p = 0.003). Compared to major alleles, minor alleles CALCRL rs6710852G and RAMP rs6431564G conferred an increased probability of being HIT‐6 RESP (for each G allele: OR = 2.82, 95% CI = 1.03–7.73, p = 0.043; OR = 2.10, 95% CI = 1.05–4.22, p = 0.037). RAMP1 rs13386048A and RAMP1 rs12465864G decreased this probability (for each rs13386048A, OR = 0.53, 95% CI = 0.28–0.98, p = 0.042; for each rs12465864G, OR = 0.32, 95% CI = 0.13–0.75, p = 0.009). A genetic risk score based on the presence and number of identified risk alleles was independently associated with HIT‐6 RESP (OR = 0.49, 95% CI = 0.33–0.72, p = 0.0003), surviving Bonferroni correction. Conclusions: Response to ERE was associated with comorbid hypertension and specific allelic variants in CALCRL and RAMP1 genes. Results require confirmation in future studies. [ABSTRACT FROM AUTHOR]