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Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
Positive and Negative Cardiovascular Effects of JAK Inhibitors in Inflammation
Aliki Zavoriti1, Pierre Miossec1
1Immunogenomics and Inflammation Research Unit, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
ACR Open Rheumatology
|June 16, 2026
Summary
Janus kinase inhibitors (JAKi) paradoxically increase cardiovascular risk in rheumatoid arthritis but benefit myeloproliferative neoplasms. This difference stems from targeting JAK2 mutations in MPNs versus broad cytokine pathways in RA, impacting cardiovascular outcomes differently.
Area of Science:
- Cardiovascular Science
- Immunology
- Hematology
Background:
- Chronic inflammation from autoimmune diseases like rheumatoid arthritis (RA) and myeloproliferative neoplasms (MPNs) accelerates cardiovascular (CV) risk via cytokines.
- Biologic therapies improve CV outcomes, but Janus kinase inhibitors (JAKi) show a paradox: potent inflammation control without proportional CV risk reduction in RA, yet therapeutic benefit in MPNs.
Purpose of the Study:
- To compare the distinct biologic mechanisms behind the JAKi CV paradox.
- To contrast JAK2 mutation-driven pathology in MPNs with cytokine-driven alterations in inflammatory diseases.
Main Methods:
- Review of distinct biologic mechanisms underlying JAKi CV paradox.
- Comparison of JAK2 mutation-driven pathology in MPNs versus cytokine-driven alterations in inflammatory diseases.
Main Results:
- JAKi are linked to increased CV events in high-risk RA patients, leading to FDA warnings.
- JAKi show therapeutic benefit in MPNs by targeting JAK2 mutations, reducing proliferation and thrombotic risk.
- CV risk in inflammatory diseases may arise from incomplete inhibition of prothrombotic pathways and potential dose-related vascular toxicity.
Conclusions:
- Understanding the binary effects of JAKi is crucial for predicting their divergent CV impact.
- Distinct mechanisms in MPNs (JAK2 targeting) versus RA (cytokine pathways) explain the observed JAKi CV paradox.
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