, easing earlier concerns that this may be one of the drug’s adverse events, an analysis of postmarketing data shows. Nevertheless, investigators noted that more research is needed to confirm that this is the case.
While randomized clinical trials have shown no increased risk of hypertension related to the drug, it has been reported in postmarketing data. However, many of these events occurred in patients with previously documented hypertension or risk factors for the disorder, the investigators noted.
The rate of hypertension adverse events in postmarketing data was 0.144 per 100 person-years. Most such reports described only one instance of elevated blood pressure. In April 2020, the prescribing information for the drug was updated to include a mention of the risk of hypertension.
“Given the limitations of postmarketing reports, including incomplete information, lack of a control arm, and others, additional data are certainly needed to fully characterize the nature, the timing, and the extent to which hypertension is a risk associated with erenumab, and indeed other [calcitonin-gene-related peptide (CGRP)] pathway antagonists,” said study investigator David W. Dodick, MD, professor of neurology at the Mayo Clinic College of Medicine, Phoenix.
The findings were presented at the American Headache Society’s 2021 annual meeting.
No increased risk over time
A monoclonal antibody and CGRP antagonist, erenumab is approved in the United States for migraine prevention in adults. CGRP medications are vasodilators, and, therefore, migraine treatments that target this pathway could theoretically have hypertensive effects.
To assess the risk of hypertension in migraine patients treated with erenumab, investigators examined clinical trial and postmarketing data. The analysis included cases with limited information and patients with a different etiology for the development of hypertension.
Using Amgen Clinical Trial data, the researchers performed a pooled safety analysis of four placebo-controlled, double-blind phase 2 or 3 studies of the drug. Participants had episodic or chronic migraine and were between ages 18 and 60 years or age 65 years. The doses studied were 70 mg and 140 mg.
In these studies, blood pressure data for each patient were based on an average of at least two measurements taken after patients were in rested state for at least 5 minutes. The position used for blood pressure measurement for each patient was consistent throughout the study.
The investigators also analyzed postmarketing reports of hypertension from May 17, 2018, to Jan. 31, 2020, identified in Amgen Global Safety data.
The pooled studies included 1,043 participants receiving placebo, 893 receiving 70 mg of erenumab, and 507 receiving 140 mg of the drug. During the treatment phase, the incidence of hypertension was 0.9% among controls, 0.8% in the 70-mg group, and 0.2% in the 140-mg group. The proportion of patients who started a new antihypertensive medication was 1.2% in controls, 0.8% in the 70-mg group, and 0.2% in the 140-mg group.
In a long-term, open-label study, patients with episodic migraine received erenumab treatment for up to 5 years. The incidence of hypertension did not increase with time in this population.
The postmarketing data encompassed 245,682 person-years of erenumab exposure. The researchers identified 362 hypertension events (355 cases). The rate of these events was 0.144 per 100 person-years. The exposure-adjusted incidence of hypertension was 1.9 per 100 patient-years for erenumab.
Of the 362 hypertensive events, 158 (43.6%) were in patients with a medical history of hypertension or risk factors for hypertension. Information about the time to onset of hypertension was available for 121 (33.4%) adverse events.
Of this group, 56 (46.2%) occurred within 1 week of erenumab initiation, including 43 (35.5%) that occurred within 1 day. This rapid time to hypertension onset “is inconsistent with the pharmacokinetic profile of once-monthly erenumab 70 mg or 140 mg, which has a peak serum concentration in approximately 6 days,” said Dr. Dodick.