CGRP monoclonal antibodies non-inferior to onabotulinumtoxinA for cerebrovascular risk in migraine patients
Background
Managing chronic migraine remains a significant challenge, particularly for patients unresponsive to conventional therapies. While onabotulinumtoxinA has been an established preventive treatment, its efficacy can be limited for some. The advent of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) offers new hope by targeting the CGRP pathway, a key mediator in migraine pathophysiology. However, real-world comparative safety data, especially concerning cerebrovascular risk in patients initiating these newer CGRP mAbs versus onabotulinumtoxinA, has been a critical gap in guiding treatment decisions.
Study Design
Researchers conducted a retrospective, active-comparator, new-user pharmacoepidemiology study utilizing the NIH All of Us Research Program Dataset. The study compared adults with migraine initiating CGRP mAbs (erenumab, fremanezumab, galcanezumab, eptinezumab) against those initiating onabotulinumtoxinA between January 2018 and September 2023. The primary outcome was ischemic stroke (IS) or transient ischemic attack (TIA) occurring more than 90 days after treatment initiation. Inverse probability of treatment weighting (IPTW) with stabilized propensity scores adjusted for 23 baseline covariates. Non-inferiority was assessed using a prespecified hazard ratio (HR) margin of 1.5.
Results
Among 16,147 patients with migraine, the primary comparison included 1,581 CGRP mAb initiators and 947 onabotulinumtoxinA initiators. IPTW effectively balanced covariates, with a maximum standardized mean difference of 0.016. For the primary outcome, 14 IS+TIA events occurred among CGRP mAb initiators, compared to 22 among onabotulinumtoxinA initiators. The hazard ratio for IS+TIA was 0.524 (95% CI 0.263-1.046).
Key Findings
- Among 16,147 migraine patients, 1,581 initiated CGRP mAbs and 947 initiated onabotulinumtoxinA.
- CGRP mAb initiators experienced 14 IS+TIA events, while onabotulinumtoxinA initiators had 22 events.
- The hazard ratio for IS+TIA was 0.524 (95% CI 0.263-1.046).
- The upper bound of the 95% CI (1.046) was below the prespecified non-inferiority margin of 1.5.
- The estimate was imprecise due to the low number of observed cerebrovascular events.
Why It Matters
This real-world evidence provides crucial reassurance regarding the cerebrovascular safety profile of CGRP mAbs relative to an established migraine preventive, onabotulinumtoxinA. For clinicians and patients navigating treatment options for migraine, particularly those with underlying cardiovascular risk, these findings suggest that CGRP mAbs do not pose a significantly higher risk of ischemic stroke or TIA. CGRP mAbs appear to offer a comparable cerebrovascular safety profile to onabotulinumtoxinA, supporting their broader use in resistant migraine. While the estimate was imprecise due to a low event count, the non-inferiority finding helps inform treatment selection, potentially expanding access to effective preventive therapies.
migraine
cgrp-mabs
onabotulinumtoxina
cerebrovascular-risk
ischemic-stroke
tia