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Managing Cardiovascular and Cancer Risk Associated with JAK Inhibitors.

Victor Yang1, Tue W Kragstrup2,3,4, Christopher McMaster1,5,6

  • 1Department of Rheumatology, Level 1, North Wing, Heidelberg Repatriation Hospital, Austin Health, 300 Waterdale Road, PO Box 5444, Heidelberg West, VIC, 3081, Australia.

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Janus kinase inhibitors (JAKi) show promise for inflammatory diseases but carry cardiovascular and cancer risks, as seen in rheumatoid arthritis trials. Careful patient selection is crucial for safe JAKi use.

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Area of Science:

  • Immunology
  • Pharmacology
  • Rheumatology

Background:

  • Janus kinase inhibitors (JAKi) are effective immune-modulating therapies for chronic inflammatory diseases.
  • Concerns about cardiovascular and cancer risks associated with JAKi have emerged, particularly from the ORAL Surveillance trial.

Purpose of the Study:

  • To review the regulatory response, data, biological plausibility, and clinical implications of cardiovascular and cancer risks associated with JAKi.
  • To guide clinicians in navigating these risks for patients considering JAKi therapy.

Main Methods:

  • Review of the ORAL Surveillance trial data and subsequent observational studies.
  • Analysis of regulatory responses and updated clinical guidelines.
  • Discussion of biological plausibility and risk-benefit considerations for JAKi use.

Main Results:

  • The ORAL Surveillance trial indicated increased risks of major adverse cardiovascular events and cancer with tofacitinib in rheumatoid arthritis patients with cardiovascular risk factors.
  • Subsequent observational data have corroborated these findings, though risks may not be evident in all patient populations.
  • Regulatory agencies have updated recommendations regarding JAKi use.

Conclusions:

  • While JAKi offer significant therapeutic benefits, their use requires careful consideration of associated cardiovascular and cancer risks.
  • Individualized patient assessment, considering risk factors and alternative treatments, is essential for optimizing JAKi therapy.
  • Further research and ongoing monitoring are necessary to fully understand and manage JAKi-related risks across diverse patient groups.