Migraine Resource Center

Migraine Resource Center

Disclosures: Breen reports no relevant financial disclosures. Co-author Juliana H. VanderPluym, MD, of the Mayo Clinic Arizona, reports grants from Amgen and personal fees from Teva.
May 19, 2021
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Microvascular complications from CGRP antagonists for migraines uncommon in Raynaud's

Disclosures: Breen reports no relevant financial disclosures. Co-author Juliana H. VanderPluym, MD, of the Mayo Clinic Arizona, reports grants from Amgen and personal fees from Teva.
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Microvascular complications from the use of calcitonin gene-related peptide antagonists for migraines are uncommon in patients with underlying Raynaud’s syndrome, according to data published in JAMA Network Open.

Calcitonin gene-related peptide (CGRP) antagonists were recently approved by the FDA in 2018 and have shown tremendous promise for the use in migraine,” Ilana D. Breen, BS, of the Mayo Clinic Arizona, told Healio Rheumatology. “CGRP is a known potent vasodilator, leading to our concern that these medications may lead to exacerbation of microvascular disease in susceptible patients, such as in those with Raynaud phenomenon.

Microvascular complications from the use of calcitonin gene-related peptide antagonists for migraines are uncommon in patients with underlying Raynaud’s syndrome, according to data derived from Breen ID, et al. JAMA Netw Open. 2021;doi:10.1001/jamanetworkopen.2021.7934.

“Raynaud phenomenon pathophysiology is known to involve diminished CGRP activity,” she added. “However, clinical trials of these novel drugs did not exclude these patients or conduct subgroup analyses of patients with primary or secondary Raynaud phenomenon. Even more, to date, prescribing recommendations for all six CGRP modulators do not list Raynaud phenomenon as a contraindication to CGRP antagonist use.”

To analyze the microvascular complications of CGRP antagonists for migraines among patients with Raynaud’s syndrome, Breen and colleagues conducted a retrospective study of individuals who received care at the Mayo Clinic Health System. From May 18, 2018, to Sept. 15, 2020, the researchers examined data from 169 adults with primary or secondary Raynaud’s syndrome, a history of migraine, and past or current CGRP-antagonist therapy.

Ilana D. Breen

The primary outcome was microvascular complications, such as worsening Raynaud’s syndrome, digital ulcerations and gangrenous necrosis, following the start of CGRP antagonists. In addition, Breen and colleagues compared the demographic and clinical characteristics of those who demonstrated complications and those who did not.

According to the researchers, 5.3% of the included patients demonstrated microvascular complications, including worsening Raynaud’s syndrome, gangrene and auto-necrosis that required distal digit amputation. In their comparative analysis, Breen and colleagues found no statistically significant differences in demographic or clinical characteristics between those with and without complications.

Among the patients who experienced complications, 55.6% had previously diagnosed Raynaud’s syndrome, with the remaining representing newly diagnosed cases. In addition, 88.9% of those with complications had chronic migraine, with or without aura. All of those who demonstrated complications were women.

The CGRP-antagonist agents temporally associated with complications were galcanezumab (Emgality; Eli Lilly & Co.), erenumab (Aimovig; Novartis, Amgen) and fremanezumab (Ajovy, Teva).

“Our results demonstrated that 5.3% of patients with underlying Raynaud phenomenon on CGRP antagonists suffered microvascular complications, ranging from worsening Raynaud phenomenon — increased frequency, duration or intensity of episodes — to digital ulceration to gangrenous necrosis requiring amputation,” Breen said. “An important point to consider is that the natural history of Raynaud phenomenon is incompletely understood. Therefore, it is difficult to determine whether the patients with Raynaud phenomenon would have experienced worsening microvascular disease regardless of exposure to CGRP antagonists.

“Therefore, follow-up studies contextualizing our findings with an enhanced understanding of the natural history of Raynaud phenomenon would be helpful,” she added. “Our study is the first original research study, to our knowledge, that assesses the microvascular risk profile of these medications in this subgroup. Our results indicate that while they are rare, the incidence of adverse microvascular events with high morbidity warrants prescribing caution of CGRP antagonists in patients with underlying Raynaud phenomenon.”