Calcitonin-gene related peptide antagonist therapy associated with microvascular complications in patients with Raynaud’s Phenomenon

1. Microvascular complications were uncommon but nevertheless observed when individuals with Raynaud’s phenomenon (RP) or scleroderma were treated with Calcitonin-gene related peptide (CGRP) antagonist therapy.

2. Microvascular complications in patients with RP included facial telangiectasia and necrosis of distal phalanges after CGRP antagonists use.

Evidence Rating: 2 (Good)

Study Rundown: Raynaud’s phenomenon (RP), a medical condition predominant in females causing pallor and pain in the toes and fingers due to cold temperatures and stress, is often associated with migraines. Recently, calcitonin-gene related peptide antagonists (CGRP) have been approved as a class of therapeutics for migraine therapy; however, its safety in individuals with RP remains unknown. The objective of this study was to characterize the complications of  CGRP usage in individuals with RP. The study involved a review of patients’ medical data from the Mayo Clinic Database (Minnesota, Arizona, Florida) which included 169 RP and scleroderma patients who have used or are currently using CGRP antagonists, and have a history of migraines. Out of the 169 patients, 9 patients suffered from microvascular complications after receiving CGRP antagonist therapy. Complications included exacerbation of RP, digital ulcerations, facial telangiectasia, hematoma, and distal phalange necrosis. Patients who had complications and those who did not were analyzed and had no significant differences amongst each other regarding demographic characteristics (sex, gender, ethnicity) and clinical characteristics. The study reveals that out of the 9 individuals who experienced complications, 4 of them were newly diagnosed with RP, implying that the duration of RP might not influence complications, although this small sample size makes drawing conclusions difficult. The researchers also found that complications in patients with RP were uncommon and not limited to one particular CGRP antagonist. Limitations to the study’s findings include the study did not report from the geographical location of their patients It was also found that the 9 patients with complications had increased β-adrenergic blockers usage. Controlling for these variables is important, as cold temperatures and use of β-Adrenergic blockers exacerbate RP symptoms. Despite these findings, the sample size who experienced complications was small; further investigations into CGRP antagonist use in individuals with RP is needed.

Click to read study in JAMA Network Open here

Relevant Reading: Raynaud’s Phenomenon Associated With Calcitonin Gene‐Related Peptide Monoclonal Antibody Antagonists

In-depth [retrospective cohort]: This study was done to investigate the possibility of complications in people with RP, who used CGRP antagonist migraine therapy from May 2018- September 2020. The search was done using data from the Mayo Clinic in Minnesota, Arizona, and Florida. The initial search for patients with RP or scleroderma had a population of 29,422. The number of patients who used CGRP antagonist from this population was 274, and from the 274 a total of 169 were selected for review based on history of migraine primary or secondary to RP. Of the 169 patients, 9 of them had complications and made up the experimental population, while the remaining 160 were the control population. The control group had a 96.3% female population with a median age of 46 (SD=14) and the experimental group had a 100% female population with a median age of 40 (SD=12). The 9 patients can be classified by 4 different groups of CGRP antagonist usage. 4 patients were on 70mg erenumab, 1 patient on 140mg erenumab, 3 patients on 120mg galcanezumab. The patients can also be categorized by the microvascular complications. 4 patients had microvascular complications which resolved without the need to stop CGRP usage, 1 patient required cessation of 70mg erenumab, 2 patients had continued complications, hematoma of finger and newly diagnosed RP requiring Nadolol chronic treatment respectively, and 2 patients had complications not associated with RP. These symptoms included persistent telangiectasia and distal phalange necrosis which required amputation.

Image: PD

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