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Anti-CGRP receptor antibodies do not modulate trigeminal pain processing: indication for distinct mechanisms of CGRP pathway blockade

Peng KP, Basedau H, Messlinger K, May A

The journal of headache and pain, 2026

46 participants

Abstract

BACKGROUND: Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptides (CGRP) are established therapies for migraine. There are currently four CGRP-mAbs available on the market: one targets the CGRP receptor, and the other three target the CGRP ligand. Despite the initial comparability of the two groups regarding efficacy, real-life data demonstrate that up to 30% of non-responders to one class exhibit a positive response to switching classes, indicating different mechanisms. The ligand-mAb, galcanezumab, has previously demonstrated a trigeminal dermatome-specific pain modulatory effect. The present study aims to evaluate the sensory modulatory effect of the receptor-mAb, erenumab. METHODS: Migraine patients were recruited in two phases. In the first phase of the study, 40 patients were included and randomly assigned to receive either erenumab 70 mg (21 patients) or a placebo (19 patients) in a double-blind manner. In the second phase of the study, 46 patients were included and received erenumab 140 mg in an open-label manner. Quantitative sensory testing (QST) parameters were measured on the right forehead (V1 dermatome) and on the forearm prior to and after treatment. A repeated-measures analysis of variance (ANOVA) was used for the statistical analysis. RESULTS: All three study cohorts (placebo, erenumab 70 mg, and erenumab 140 mg) were comparable in terms of demographics, including age, sex ratio, and baseline headache frequency, and showed no statistically…

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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 46 participants or records.

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