Treatment with galcanezumab in patients with episodic and chronic migraine does not result in changes in hemodynamic parameters or increase the risk of cardiovascular (CV) events, according to study results published in Headache.
Galcanezumab, a humanized IgG4 monoclonal antibody that binds calcitonin gene-related peptide, is approved for the preventive treatment of migraine in adults. Because the CV effects of galcanezumab are not clear, the researchers assessed the effect of galcanezumab, compared with placebo, on blood pressure, changes in electrocardiograms, and CV events in patients with episodic or chronic migraine.
The researchers used data from 3 phase 3, double-blind, placebo-controlled studies of patients aged 18-65 years: 2 similar 6-month studies that included patients with episodic migraine (EVOLVE-1 and EVOLVE-2) and a single 3-month study of patients with chronic migraine (REGAIN). The subjects were randomized (1:1:2) to monthly subcutaneous injections of galcanezumab 120 mg, galcanezumab 240 mg, or placebo.
Treatment comparisons for CV treatment-emergent adverse events (TEAEs), and categorical and mean changes in blood pressure, pulse, and electrocardiograms were evaluated.
A total of 705 patients were treated with galcanezumab 120 mg, 730 patients were treated with galcanezumab 240 mg, and 1451 patients were in the placebo group. Of the 2886 adults included in the analysis, 1773 patients had episodic migraine and 1113 had chronic migraine.
The frequency of at least 1 CV TEAE was 2.6% (18 cases) for galcanezumab 120 mg, 3.3% (24 cases) for galcanezumab 240 mg, and 2.9% (42 cases) for placebo, with no significant differences between the groups (galcanezumab 120 mg vs placebo: odds ratio 0.9; 95% CI, 0.5-1.5; galcanezumab 240 mg vs placebo: odds ratio 1.1; 95% CI, 0.7-1.9).
Researchers noted there were no likely CV TEAEs documented in the 8 galcanezumab-treated patients with a history of ischemic central nervous system vascular conditions, cardiomyopathy, or cardiac failure.
Serious CV adverse events were documented in 3 patients (0.4%) treated with galcanezumab 240 mg (pulmonary embolism, myocardial infarction, and transient ischemic attack) and in 3 (0.2%) placebo-treated patients (pulmonary embolism, deep vein thrombosis, and myocardial infarction), whereas in the group of patients treated with galcanezumab 120 mg, there were no serious events.
Compared with placebo, galcanezumab treatment for up to 6 months did not lead to mean increases in blood pressure or pulse. Overall, the percentage of patients with increases in blood pressure or pulse were similar among patients treated with galcanezumab compared with those receiving placebo.
The researchers noted the study had several limitations, including short treatment duration, low frequency of CV events, and exclusion of patients with acute or serious CV risk or serious medical conditions.
“The data from this integrated analysis do not suggest that galcanezumab treatment in patients with migraine resulted in hemodynamic changes consistent with vasoconstriction or an increase in CV [cardiovascular] adverse events, including those related to ischemia up to 6 months of treatment,” concluded the researchers.
Disclosure: This clinical trial was supported by Eli Lilly and Company. Please see the original reference for a full list of authors’ disclosures
Oakes TM, Kovacs R, Rosen N, et al. Evaluation of cardiovascular outcomes in adult patients with episodic or chronic migraine treated with galcanezumab: data from three phase 3, randomized, double-blind, placebo-controlled EVOLVE-1, EVOLVE-2, and REGAIN studies. [published online ahead of print, 2019 Nov 13]. Headache. 2019;10.1111/head.13684. doi:10.1111/head.13684