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CGRP-mediated trigeminovascular reactivity in migraine patients treated with erenumab
  1. Simone de Vries Lentsch1,
  2. Linda Al-Hassany2,
  3. Michel Dominique Ferrari1,
  4. Gisela Marie Terwindt1,
  5. Antoinette MaassenVanDenBrink2
  1. 1Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
  1. Correspondence to Antoinette MaassenVanDenBrink, Erasmus MC, Rotterdam, The Netherlands; a.vanharen-maassenvandenbrink{at}erasmusmc.nl

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Introduction

Migraine is a highly disabling disorder characterised by recurrent attacks of severe headache (https://ichd-3.org/). The trigeminovascular system and release of calcitonin gene-related peptide (CGRP), a neuromodulator and potent vasodilator, have a crucial role in the pathophysiology of migraine.1 Monoclonal antibodies targeting CGRP (eptinezumab, fremanezumab, galcanezumab) or its receptor (erenumab) are novel prophylactics. Unfortunately, it is currently unknown which mechanisms are underlying the variability in response rates.

In addition to spontaneous release during migraine, CGRP can be released from trigeminal nerve endings by external stimuli. Application of capsaicin on the forehead releases CGRP via activation of the transient receptor potential cation channel subfamily V member 1 of the trigeminal nerve and thereby increases forehead dermal blood flow (DBF).2 Forearm application of capsaicin also increases DBF and this effect can be inhibited by erenumab, but the dose–response relationship in this model does not seem to be indicative for clinical responses.3

We evaluated whether erenumab inhibits the forehead capsaicin-induced DBF response and whether the degree of capsaicin-induced DBF response before treatment is different in patients with an adequate versus suboptimal clinical response to erenumab.

Materials and methods

Migraine patients were recruited from the Leiden Headache Centre. Patients were not using any other migraine prophylactics and had no medication overuse headache.

Approval was obtained from the Leiden University Medical Center Medical Ethical Committee and all participants gave written informed consent.

Clinical efficacy

A validated daily headache E-diary4 was used to assess the occurrence and characteristics of headache and accompanying symptoms. The clinical response was assessed by comparing monthly migraine days (MMD) in week 9–12 (ie, after three doses of erenumab) to that in the 4 weeks pretreatment baseline period. Participants were divided into those …

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Footnotes

  • MDF, GMT and AM contributed equally.

  • Contributors SdVL, MDF, GT and AMVB contributed to conception and design of the study. SdVL, LA-H, GT and AMVB contributed to the acquisition and analysis of data. SdVL, LA-H, MDF, GT and AMVB contributed to drafting the text or preparing the figures.

  • Funding This work was supported by grants of the Dutch Research Council (NWO; Spinoza Award 2009 to MDF and VICI grant 09150181910040 to AMVB).

  • Competing interests AMVB reports consultancy or industry support from Novartis, Lilly and Teva, who are all three companies that are marketing CGRP (receptor) monoclonal antibodies, and independent support from the Dutch Research Council and the Dutch Heart & Brain Foundations. GT reports consultancy support from Novartis, Lilly, Teva (see above), Allergan and independent support from Dutch Research Council, and the Dutch Heart & Brain Foundations. SdVL, LA-H and MDF have no conflict of interest to declare.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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