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Cephalalgia. 2019 Jul 8:333102419863027. doi: 10.1177/0333102419863027. [Epub ahead of print]

Characterisation of vasodilatory responses in the presence of the CGRP receptor antibody erenumab in human isolated arteries.

Author information

1
1 Division of Pharmacology, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
2
2 Department of Cardiothoracic Surgery, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
3
3 Department of Neurosurgery, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
4
4 Amgen Inc, Thousand Oaks, CA, USA.
5
5 Novartis Pharma AG, Basel, Switzerland.

Abstract

BACKGROUND:

Migraine is associated with activation of the trigeminovascular system, release of calcitonin gene-related peptide (CGRP) and dilation of dural arteries. Novel treatments target calcitonin gene-related peptide or its receptor, which are present in all vascular beds, raising cardiovascular concerns. Erenumab is a human CGRP-receptor antibody approved for the prophylactic treatment of migraine.

METHODS:

We characterised the relaxant responses to CGRP in the absence and presence of erenumab (1 μM) in isolated human middle meningeal, internal mammary and (proximal and distal) coronary arteries. Furthermore, in human internal mammary arteries from cardiovascularly-compromised patients, we assessed the pharmacological specificity of erenumab by investigating whether the vasodilatory responses to acetylcholine, sodium nitroprusside, pituitary adenylate cyclase activating polypeptide-38 (PACAP), vasoactive intestinal peptide and nicardipine, along with the vasoconstrictor responses to dihydroergotamine, were modified by erenumab.

RESULTS:

Calcitonin gene-related peptide induced concentration-dependent vasodilatory responses in all vessels studied that were significantly antagonised by erenumab. In human internal mammary arteries from cardiovascularly-compromised patients, the responses to acetylcholine, sodium nitroprusside, PACAP, vasoactive intestinal peptide, nicardipine and dihydroergotamine were unaffected by erenumab.

CONCLUSION:

Erenumab inhibits calcitonin gene-related peptide-induced vasodilatory responses in human middle meningeal arteries, human internal mammary arteries and human coronary arteries. Moreover, erenumab shows functional specificity as no interaction was observed with the relaxant responses to several vasodilators, nor the dihydroergotamine-dependent vasoconstrictor responses.

KEYWORDS:

Cardiovascular safety; coronary arteries; mammary arteries; meningeal arteries; migraine

PMID:
31284729
DOI:
10.1177/0333102419863027

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