The migraine medication erenumab appears to pose no increased risk of hypertension, easing earlier concerns that this may be one of the drug’s adverse events, an analysis of postmarketing data show. Nevertheless, investigators note 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 note.
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 in Phoenix, Arizona.
The findings were presented at the virtual American Headache Society (AHS) Annual Meeting 2021.
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 January 31, 2020, identified in Amgen Global Safety data.
The pooled studies included 1043 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 Dodick.
Hypertension “Not a Barrier” to Treatment
Commenting on the findings for Medscape Medical News, Richard B. Lipton, MD, Edwin S. Lowe professor and vice chair of neurology at Albert Einstein College of Medicine in the Bronx, New York, noted that while in theory blocking CGRP could increase blood pressure. However, he noted that the data and clinical experience do not suggest erenumab poses a serious risk.
“I have rarely seen new onset hypertension with erenumab in the patients treated at our medical center. The few cases I have seen were in older adults with pre-existing hypertension,” he said.
The investigators’ review of clinical trial data, together with global safety databases was a strength of their study, said Lipton. In clinical trials, patients are monitored carefully, and a placebo control group aids in the determination of background rates.
“In the trials, the incidence of new-onset hypertension or hypertension exacerbation was 0.9%, while the placebo rate was 0.2%,” said Lipton. “The absolute increase in the risk of hypertension was 0.6% or six cases per thousand: a low rate.” But clinical trials enroll carefully selected patients who do not represent the broad group of people treated with erenumab in clinical practice, he added.
The global safety data are more representative of patients who receive erenumab in real-world settings. The weaknesses of these data, though, are the lack of a control group and the incomplete ascertainment of data associated with spontaneous reporting.
Yet both types of studies, with their complementary strengths and weaknesses, indicated low rates of hypertension.
“The low incidence of hypertension, in my view, is not a barrier to the use of erenumab, though checking blood pressure after starting any new migraine therapy is prudent,” Lipton concluded.
The study was funded by Amgen. Dodick had no relevant disclosures. Lipton has consulted for and conducted studies funded by Amgen and by other companies that manufacture CGRP drugs. He has stock options in Biohaven.
American Headache Society (AHS) Annual Meeting 2021: Abstract IOR-08. Presented June 3, 2021.
Follow Erik Greb on Twitter: @MedscapeErik.