PACAP38-induced migraine attacks are independent of CGRP signaling: a randomized controlled trial
Abstract
BACKGROUND: Calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) are key pathogenic drivers of migraine. While CGRP has become the target of several mechanism-based therapies, less is known about PACAP38 signaling in migraine pathogenesis. Previous studies suggest that PACAP38 can modulate CGRP release, but it might also induce migraine attacks via CGRP-independent mechanisms. Whether PACAP38 signaling is independent of and parallel to CGRP signaling has implications for future therapeutic strategies. Here, we aimed to ascertain whether PACAP-38 can mediate migraine attacks independently of CGRP signaling by assessing the ability of eptinezumab to prevent PACAP38-induced migraine attacks.
METHODS: In a double-blind, placebo-controlled, parallel-group study, we randomly allocated adults with migraine without aura to receive either an intravenous infusion of 300-mg eptinezumab or matching placebo (isotonic saline) over 30 min. Two hours post-infusion, all participants were administered PACAP38 intravenously at 10 pmol/kg/min for 20 min. The primary endpoint was the incidence of migraine attacks during the 24-hour observational period post-infusion of eptinezumab or placebo. Key secondary endpoints included between-group differences in incidence of headache, and area under the curve (AUC) for headache intensity scores, diameter of the superficial temporal artery (STA) and facial skin blood flow.
RESULTS: A total of 38…
How strong is the evidence?
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: 38 participants or records.
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