Evaluation of the Safety of Calcitonin Gene-Related Peptide Antagonists for Migraine Treatment Among Adults With Raynaud Phenomenon

Ilana D Breen,Mark R Pittelkow,Caitlin M Brumfiel,Leroy Griffing,Richard J Butterfield,Meera H Patel,Juliana H Vanderpluym,Aaron R Mangold

doi:10.1001/jamanetworkopen.2021.7934

Ilana D Breen, Mark R Pittelkow + Show 6 more

Open Access

https://doi.org/10.1001/jamanetworkopen.2021.7934

Copy DOI

Abstract

Calcitonin gene-related peptide (CGRP) antagonists have demonstrated tremendous promise in migraine management. However, these medications decrease reflex vasodilatory response, which may lead to exacerbation of microvascular disease in susceptible patients, such as patients with Raynaud phenomenon (RP). To investigate the microvascular complications of CGRP antagonists in patients with underlying RP. This retrospective cohort study was performed from May 18, 2018, to September 15, 2020, in Mayo Clinic Health System patients with Raynaud phenomenon while undergoing CGRP antagonist therapy to treat migraine. Inclusion criteria were age older than 18 years, history of migraine, past or current treatment with CGRP antagonists, and diagnosis of primary or secondary RP. Treatment with CGRP antagonists. The main outcome measure was microvascular complications (eg, worsening RP, digital ulcerations, and gangrenous necrosis) after initiation of treatment with a CGRP antagonist. Patient demographic and clinical characteristics were compared between those who experienced complications and those who did not. A total of 169 patients (163 [96.4%] female; 151 [89.3%] non-Hispanic White; mean [SD] age, 46 [13] years) were identified. Of the 169 patients, 9 (5.3%) exhibited microvascular complications, ranging from worsening RP to gangrene and autonecrosis that required distal digit amputation. Comparative analysis did not find statistically significant differences in demographic or clinical characteristics between the 2 cohorts. All 9 patients with complications were female (mean [SD] age, 40 [12] years). Five of the 9 patients (55.6%) had previously diagnosed RP; in 3 the RP was primary, and 2 it was secondary to scleroderma. The other 4 patients (44.4%) were newly diagnosed with RP. Eight of the 9 patients (88.9%) had chronic migraine; 4 had migraine with aura, and 5 had migraine without aura. The CGRP antagonist agents temporally associated with the microvascular complications included galcanezumab (in 3 patients), erenumab (in 5 patients), and fremanezumab (in 1 patient). The results of this study indicate that microvascular complications of CGRP antagonist use in patients with underlying RP are uncommon. The incidence of serious adverse events, although rare, warrant caution when considering the use of these agents in patients with RP.

Highlights

The calcitonin gene-related peptide (CGRP) antagonist agents temporally associated with the microvascular complications included galcanezumab, erenumab, and fremanezumab
The results of this study indicate that microvascular complications of CGRP antagonist use in patients with underlying Raynaud phenomenon (RP) are uncommon
Meaning This study suggests that microvascular complications are uncommon in patients with Raynaud phenomenon who are taking CGRP antagonists; the incidence of adverse microvascular events with high morbidity warrants caution in prescribing CGRP antagonists in these patients

Summary

Introduction

A new class of medications known as calcitonin gene-related peptide (CGRP) inhibitors has been recently approved for the treatment of episodic and chronic migraine. There are 2 types of available CGRP inhibitors: (1) monoclonal antibodies that bind the CGRP receptor or ligand and (2) smallmolecule CGRP receptor antagonists. These medications suppress activity of CGRP, a neuropeptide located in the peripheral and central nervous system that is involved in pain modulation, in the trigeminovascular system. There are fewer CGRP-supplying nerves, and in RP, there may be CGRP deficiency in the distal or acral skin.[2,3] Cutaneous blood flow increases in these patients after CGRP infusion.[3,4] A previous study[5] examined the effects of systemic therapy with calcitonin in patients with scleroderma, finding a reduction of digital ulceration and improvement in pulmonary function after infusion. The use of CGRP antagonists was associated with digital ulceration in 2 patients with underlying RP.[6]

Methods

Results

Discussion

Conclusion