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

Question In patients with Raynaud phenomenon, what is the microvascular complication risk of calcitonin gene-related peptide (CGRP) antagonist use? Findings In this cohort study of 169 adults with Raynaud phenomenon, 9 patients had microvascular complications after CGRP antagonist use. Two of the 9 patients had severe adverse events, including digital autonecrosis that required distal amputation. Meaning This study suggests that microvascular complications are uncommon in patients with Raynaud phenomenon who are taking CGRP antagonists; however, the incidence of adverse microvascular events with high morbidity warrants caution in prescribing CGRP antagonists in these patients. Importance 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). Objective To investigate the microvascular complications of CGRP antagonists in patients with underlying RP. Design, Setting, and Participants 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. Exposure Treatment with CGRP antagonists. Main Outcomes and Measures 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. Results 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). Conclusions and Relevance 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. This cohort study investigates microvascular complications associated with calcitonin gene-related peptide (CGRP) antagonists in patients with underlying Raynaud phenomenon.

Automated summary

The study found that microvascular complications of CGRP antagonist use in patients with underlying RP are uncommon, but caution is still needed when considering the use of these agents in these patients.