Cardiovascular safety of genetically proxied IL-5 inhibition: a Mendelian randomisation study

Philip Alton, David M. Hughes, Sizheng Steven Zhao

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Interleukin-5 (IL-5) inhibitors have revolutionised management of eosinophilic asthma, but IL-5 is thought to play a protective role in atherosclerosis and cardiovascular safety data are scarce. We used population-level data to examine the association between genetically proxied IL-5i and risk of cardiovascular diseases.

Methods. Genetic instruments for IL-5i were selected from a genome-wide association study of eosinophil count in 563,946 individuals. Genetic association data for coronary artery disease were obtained from 60,801 cases, 40,585 stroke cases, 7,988 venous thromboembolism cases, and up to 406,111 controls. We used the inverse-variance weighted method and a series of sensitivity analyses.

Results. Nine genetic variants were selected to instrument IL-5i. Genetically proxied IL-5i was not associated with risk of coronary heart disease (OR 0.82, 95%CI 0.65-1.03), stroke (OR 1.10; 0.95-1.27), or venous thromboembolism (OR 0.87; 0.64-1.17).

Conclusion. These results suggest that IL-5i is unlikely to increase risk of adverse cardiovascular and thromboembolic events.
Original languageEnglish
JournalRespiratory Investigation
Publication statusAccepted/In press - 16 Dec 2022

Keywords

  • IL-5
  • asthma
  • cardiovascular safety
  • Mepolizumab
  • genetic instrumental variable

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