CGRP Medication Erenumab Does Not Result in Increased Vascular Risk

In a recently published retrospective study using MarketScan medical claims data, results showed that patients on erenumab (Aimovig; Amgen), an FDA-approved medication for migraine, had a similar rate of vascular events than other anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) or onabotulinumtoxinA. Overall, this real-world study highlighted the lack of increased risk of cardiovascular (CVD) or cerebrovascular events with erenumab.

After accounting for drug switching, the study analyzed 108,019 patients across the 4 treatment groups: erenumab (n = 19,220), other anti-CGRP pathway mAbs (n = 23,244), standard oral preventive medications (n = 53,842), and onabotulinumtoxinA (n = 11,713). Over a 12-month period, the overall cumulative risk (CR) of hypertension was 9.34% in the erenumab group, 9.42% for other anti-CGRP pathway mAbs, 9.09% for standard oral preventive medications, and 9.10% for onabotulinumtoxinA. Notably, stratified analyses showed greater risk of hypertension among those with a history of CVD or a history of risk factors for CVD.

Led by David W. Dodick, MD, a professor of neurology at Mayo Clinic Scottsdale, the unadjusted CR of acute myocardial infarction (MI) at 36 months were as follows: erenumab, 0.41% (95% CI: 0.22–0.59%); other anti-CGRP mAbs, 0.39% (95% CI: 0.25–0.52%); standard oral preventives, 0.53% (95% CI: 0.38–0.67%); and onabotulinumtoxinA, 0.49% (95% CI: 0.24–0.73%). For stroke, the unadjusted CRs were: erenumab, 0.91% (95% CI: 0.61–1.22%); other anti-CGRP mAbs, 0.93% (95% CI: 0.68–1.17%); standard oral preventives, 1.07% (95% CI: 0.93–1.22%); and onabotulinumtoxinA, 1.22% (95% CI: 0.77–1.67%).

This study's strength lay in its use of real-world data from more than 100,000 patients, offering a broader comparison of cardiovascular risks across migraine preventives. Unlike previous trials, it compared treatments against each other, not just placebo. While unadjusted risk estimates for hypertension aligned with trial data, the study acknowledged limitations in drawing conclusions about new-onset hypertension due to unbalanced baseline characteristics and differential drop-out.

Before comparing the relative risks (RRs) of acute MI or stroke between the erenumab and other treatment groups, baseline covariates and potential biases were assessed for comparability. Significant imbalances were found when comparing erenumab to standard oral preventives, leading to exclusion of extreme propensity score (PS) weights using a 1% trim. However, the comparison failed to converge, preventing RR estimation. For erenumab versus other anti-CGRP mAbs, no trimming was needed due to adequate PS overlap. For erenumab versus onabotulinumtoxinA, a 1% PS trim was applied after excluding prior botulinum toxin exposure. Ultimately, the NCO analyses showed minimal residual bias in the comparisons.

The adjusted 36-month CR curves for acute MI or stroke were similar between the erenumab and other anti-CGRP pathway mAbs groups under an intent-to-treat (ITT) follow-up model, with no drug switching observed within ±1 year of patients' index date in the comparative analyses. For comparison, the adjusted CR for acute MI was 0.37% (95% CI, 0.24-0.59%) for the erenumab group vs 0.37% (95% CI, 0.26-0.52) for other anti-CGRP pathway mABs. Overall, the RR acute MI with erenumab vs other anti-CGRP pathway mAbs was 1.02 (95% CI, 0.45-1.59).

Top Clinical Takeaways

1. Comparable Cardiovascular Risk: The study found similar rates of acute MI and stroke for erenumab, other anti-CGRP mAbs, and onabotulinumtoxinA, indicating no increased cardiovascular risk with erenumab.

2. Hypertension Risk: The risk of hypertension was consistent across treatment groups, with stratified analyses showing higher risk in patients with a history of CVD or risk factors.

3. Real-World Data Strength: The study’s use of real-world data from over 100,000 patients provided a broader and more direct comparison of cardiovascular risks across migraine preventives than previous clinical trials.

The adjusted stroke CR (95% CI) was 0.84% (0.64–1.10%) for the erenumab group and 0.94% (0.71–1.23%) for the other anti-CGRP pathway mAbs group, with a stroke RR (95% CI) of 0.90 (0.56–1.25) for erenumab versus other anti-CGRP mAbs. Stratified analyses generally showed comparable risks of acute MI or stroke between erenumab and other anti-CGRP mAbs in strata with sufficient outcomes, although some strata had small event numbers, resulting in wide CIs.

Erenumab, approved by the FDA in 2018, is a CGRP receptor antagonist, meaning it blocks the activity of CGRP, a neuropeptide implicated in the process of migraine attacks. The therapy is a once-monthly treatment administered through an auto-injector, making it a convenient option for patients who require long-term prevention of migraines. Common adverse events (AEs) associated with erenumab, as shown in its pivotal trials, were injection site reactions, constipation, and muscle cramps.²