During the double-blind treatment phase, rates of hypertension AEs were low for the placebo and erenumab 70- and 140-mg treatment groups, as well as during open-label erenumab treatment.
Analyses of clinical trial and postmarketing data revealed no evidence of increased risk for hypertension in patients with migraine treated with erenumab (Aimoig; Novartis), an FDA-approved monoclonal antibody that targets calcitonin gene-related peptide (CGRP) receptor.1
Despite no previous evidence of hypertension during the clinical development program, concerns were raised after adverse events (AEs) of hypertension were identified in the postmarketing setting. Erenumab was approved in May 2018 as a self-administered once monthly preventive treatment. Lead author David W. Dodick, MD, professor of neurology, Mayo Clinic Scottsdale, and colleagues aimed to understand the risk by performing a pooled analysis of 4 phase 2 and phase 3 clinical trials identified from May 17, 2018, through January 31, 2020.
At the conclusion of the study, the incidence of hypertension AEs (placebo: 9 of 1043 [0.9%]; erenumab 70 mg: 7 of 893 [0.8%]; erenumab 140 mg: 1 of 507 [0.2%]), exposure-adjusted incidence of hypertension AEs (3.6 [95% CI, 1.2-5.9]; 3.3 [95% CI, 0.8-5.7]; and 0.8 [95% CI, 0.0-2.4] per 100 patient-years, respectively), and percentage of patients initiating medication to treat hypertension (n = 12 [1.2%]; n = 7 [0.8%]; n = 1 [0.2%], respectively) during the double-blind treatment phase were similar across treatment groups. Regardless of dosage, there were no reported cases of serious hypertension AEs.
The study authors concluded that, "additional data are needed to fully characterize those at risk, as well as the nature, timing, and extent to which hypertension is a risk associated with erenumab and other CGRP-pathway antagonists.”
Previously conducted analysis of postmarketing reports treatment with erenumab by Suprat Saely, PharmD, BCPS, FCCM, et al. showed AEs of elevated blood pressure (BP) or hypertension, raising concern.2 In April 2020, the US Prescribing Information for erenumab was updated to include the risk of hypertension based on postmarketing experience.3
In the postmarketing surveillance using the Amgen Global Safety Database investigators observed a total of 362 AEs in 355 cases during the specified time frame (a total of >245,000 patient-years of exposure). This resulted in an exposure-adjusted incidence rate of 0.144 per 100 patient-years, indicating that hypertension AEs were reported for 1.4 patients out of every 1000 patients treated annually.1
Continued analysis of this group showed that most of the patients were women (73.5%), with a median age of 53 (range, 24-87) years. In total, 26.2% (n = 95) of these cases were determined to be serious and 47 individuals had BP data available. Of those, 21 reached American Heart Association criteria for hypertensive crisis (systolic BP >180 mm Hg and/or diastolic BP >120 mm Hg) based on available systolic or diastolic BP level measured by patients or healthcare professionals.
Previously documented diagnosed hypertension was the most common risk factor (33.7% [32 of 95]) of hypertension-related serious AEs and nonserious hypertension AEs (11.2% [30 of 267]). Other potential risk factors such as diabetes, cardiovascular disease, obstructive sleep apnea, obesity, and thyroid disease, followed as some of the most common event characteristics. Notably, other potential risk factors were unknown for approximately half of the events.
Earlier this year, data from the notable LIBERTY study (NCT03096834) found erenumab to produce greater improvements in patient-reported outcomes of migraine-related functional and physical impairment, work productivity, and everyday activities compared to placebo in those who have failed 2-4 previous medications.4