Risk of hypertension in erenumab‐treated patients with migraine: Analyses of clinical trial and postmarketing data

Abstract

Objective To assess the risk of hypertension in patients with migraine who received erenumab in clinical trials and in the postmarketing setting. Background Erenumab is a monoclonal antibody for migraine prevention that targets the calcitonin gene‐related peptide (CGRP) receptor. Hypertension is a theoretical risk for inhibitors of the CGRP pathway. Although no evidence of an association between erenumab treatment and hypertension was observed during the clinical development program, adverse events (AEs) of hypertension have been identified in the postmarketing setting. Methods Safety data from four phase 2 and phase 3 clinical trials were used to perform a pooled analysis of hypertension AEs in patients with migraine receiving erenumab. Postmarketing AEs of hypertension were identified from the Amgen Global Safety database from May 17, 2018, through January 31, 2020. Results In the pooled analysis of clinical trials, hypertension AEs (placebo, 9/1043 [0.9%]; erenumab 70 mg, 7/893 [0.8%]; erenumab 140 mg, 1/507 [0.2%]) and percentage of patients initiating medication to treat hypertension (12/1043 [1.2%], 7/893 [0.8%], 1/507 [0.2%], respectively) were similar across treatment groups. A total of 362 AEs of hypertension were identified from the postmarketing setting, 26.2% (95/362) of which were serious, >245,000 patient‐years of exposure. The exposure‐adjusted incidence of hypertension was 0.144 per 100 patient‐years. Conclusions Clinical trials did not demonstrate an increased risk of hypertension with erenumab compared with placebo, and AE rates of hypertension reported with erenumab in the postmarketing setting were generally low. Additional data are needed to fully characterize the extent to which hypertension is a risk associated with erenumab.

Migraine Prevention with Erenumab: Focus on Patient Selection, Perspectives and Outcomes

“…Researchers extensively studied mAbs for the risk of cardiovascular adverse events; however, no safety concerns emerged, even after 5 years of treatment. 29 Arterial hypertension is another relevant vascular adverse event, whose connection with erenumab is yet to be proved: a recent analysis of RCT data showed that the proportion of patients developing this condition was <1%, similar to the placebo groups of RCTs, and not relevant in a post-marketing setting; 72 conversely, a retrospective descriptive study reported 61 cases of new-onset arterial hypertension shortly after treatment start. 13 We would need larger post-marketing analyses evaluating connections and frequency of arterial hypertension occurring during erenumab treatment as well as comparative studies with the other anti-CGRP mAbs.…”

Role of Atogepant in the Treatment of Episodic Migraines: Clinical Perspectives and Considerations

“… 65 However, post-marketing surveillance of erenumab revealed an association with hypertension. 66 Ubrogepant has not demonstrated a difference in AEs or cardiac AE in patients with moderate-high cardiovascular risk factors. 67 There is concern for inhibiting CGRP in patients with small vessel diseases, such as Raynaud’s phenomenon (RP) cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).…”

Efficacy of erenumab and factors predicting response after 3 months in treatment resistant chronic migraine: a clinical service evaluation

“…Due to the vasodilatory action of CGRP particular attention has been paid to the potential effects on blood pressure [23]. Clinical trials did not show a significant risk of hypertension with erenumab but it has been reported in post-marketing surveillance [24,25] and is now included as a warning on the package insert in the US [26]. We found a statistically significant rise in systolic BP following 3 months of erenumab treatment but the magnitude of this was very small (2.4 mmHg) and therefore of questionable clinical significance.…”