Plasma CGRP Levels in Migraine: A Registry for Migraine Study.

Abstract (English)

BACKGROUND AND OBJECTIVES: Calcitonin gene-related peptide (CGRP) plays a central mechanistic role in migraine and is an established drug target. However, it remains unclear whether peripheral plasma CGRP levels meaningfully reflect disease activity. We investigated whether circulating plasma CGRP differs between individuals with migraine and healthy controls and whether concentrations vary across migraine subtypes, clinical status, and preventive treatment use. METHODS: This cross-sectional observational study enrolled adults (≥18 years) with migraine with aura, migraine without aura, or chronic migraine primarily from specialized care. Healthy controls without personal or first-degree family history of primary headache disorders were mainly recruited through web-based advertisement. Venous blood was obtained by antecubital phlebotomy, and plasma CGRP was quantified in duplicate using a validated high-affinity radioimmunoassay. Controls were matched 1:4 to participants with migraine on age, sex, body mass index, and storage duration. The primary outcome was between-group difference in plasma CGRP concentrations. Group comparisons were performed using Mann-Whitney <i>U</i> tests. Regression models were performed to assess associations with clinical variables. RESULTS: A total of 588 participants with migraine and 147 matched controls were analyzed (mean age 43.1 &#xb1; 11.9 vs 41.5 &#xb1; 11.5 years; 88.8% vs 85.7% female). The median (interquartile range) plasma CGRP concentrations were lower in participants with migraine compared with controls (125 [68-173] vs 151 [118-199] pmol/L; <i>p</i> < 0.001). Subgroup analyses revealed no significant differences across subtypes (episodic vs chronic, with aura vs without aura), ictal vs interictal status, or preventive medication use (all <i>p</i> > 0.05). Sensitivity analyses restricted to headache-free participants confirmed the principal findings, demonstrating lower plasma CGRP concentrations across all migraine subgroups compared with controls (all <i>p</i> < 0.001). Multivariable models identified no clinical predictors of plasma CGRP levels. Sample storage duration did not correlate with measured levels (Spearman <i>&#x3c1;</i> = -0.032; <i>p</i> = 0.37). DISCUSSION: Plasma CGRP concentrations were modestly lower in migraine and did not vary by clinical subtype or disease state. These findings challenge the assumption that migraine is characterized by elevated circulating CGRP and suggest limited utility of plasma CGRP as a disease biomarker.