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.

Assessment of Bone Mineral Density Over 1 Year in a Cross-Sectional Cohort of Migraine Patients Receiving Anti-CGRP Monoclonal Antibodies.

BACKGROUND: Calcitonin gene-related peptide (CGRP), implicated in migraine pain, also possesses bone anabolic properties, which leads to the possibility that monoclonal antibodies targeting CGRP (anti-CGRPs) might increase the risk of bone density abnormalities. OBJECTIVE: The objective of this study was to explore bone mineral density abnormalities in a cohort of migraine patients treated with anti-CGRPs. METHODS: This was a single-center, cross-sectional, cohort study including migraine patients who underwent a densitometry assessment during anti-CGRP treatment. We assessed the frequency of osteopenia or osteoporosis (OSTEO+ status), defined as a bone mineral density T-score of -1 to -2.5, and <-2.5 standard deviations from the young female adult mean, respectively. Additionally, the association of OSTEO+ status with anti-CGRP treatment duration and primary osteoporosis' risk factors was investigated using logistic regression models. RESULTS: Data from 51 patients (43 female, mean age 46 ± 13.9 years) were evaluated. The mean duration of anti-CGRP treatment was 15.7 (±11.8) months. Twenty-seven patients (53%) were OSTEO+ (n = 22 osteopenia; n = 5 osteoporosis). In the final model, menopause [odds ratio 11.641 (95% confidence interval 1.486-91.197), p = 0.019] and anti-seizure drug use [odds ratio 12.825 (95% confidence interval 1.162-141.569), p = 0.037] were associated with OSTEO+ status. CONCLUSIONS: In our cohort of migraine patients, no evidence of an association between anti-CGRP treatment duration and an increasing risk of bone mineral density abnormalities was found. However, these findings are preliminary and necessitate further longitudinal research with larger cohorts and extended follow-up to be validated.