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

Chiara Zecca; Salvatore Terrazzino; Davide Para; Giovanna Campagna; Michele Viana; Christoph J Schankin; Claudio Gobbi

doi:10.1111/ene.15678

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

Eur J Neurol. 2023 Apr;30(4):1099-1108. doi: 10.1111/ene.15678. Epub 2023 Jan 24.

Authors

Chiara Zecca^{1

2}, Salvatore Terrazzino³, Davide Para¹, Giovanna Campagna¹, Michele Viana^{1

4}, Christoph J Schankin⁵, Claudio Gobbi^{1

2}

Affiliations

¹ Department of Neurology, Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland.
² Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
³ Department of Pharmaceutical Sciences and Interdepartmental Research Center of Pharmacogenetics and Pharmacogenomics, University of Piemonte Orientale "A. Avogadro", Novara, Italy.
⁴ Headache Group, Department of Basic and Clinical Neurosciences, King's College London, London, UK.
⁵ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

PMID: 36627267
DOI: 10.1111/ene.15678

Abstract

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.

Keywords: anti-CGRP antibodies; erenumab; hypertension; migraine; patient-reported outcomes; treatment response.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Cohort Studies
Headache
Humans
Hypertension*
Migraine Disorders* / drug therapy
Prospective Studies

Substances

erenumab