Thromboembolic adverse drug reactions in janus kinase (Jak) inhibitors: Does the inhibitor specificity play a role?
Authors
Kotyla, Przemysław J.Engelmann, Małgorzata
Giemza-Stokłosa, Joanna
Wnuk, Bartosz
Islam, Md Asiful
Issue Date
2021-02-28
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Recent advances in immunology enabled the characterization of several signal transmitting pathways responsible for proper cytokine and chemokine signaling. Among them, Janus kinases (JAKs) are essential components of receptor activation systems. The discovery of JAK kinases enabled the synthesis of JAK kinase inhibitors (JAKi or Jakinibs), which have proven to be efficacious in the treatment of hematologic malignancies and several rheumatological disorders and continue to be investigated in many clinical indications. Blocking multiple cytokines belonging to several cytokine families with a single small molecule may, however, create a potential risk for the patients. Recently, a higher risk of thromboembolic complications, namely, deep vein thrombosis and pulmonary embolism, has been recognized as the main concern during treatment with Jakinibs. At present, it is not entirely clear whether this increased risk is related to direct cytokine blockade, the presence of concomitant diseases in treated patients or other unknown circumstances that work together to increase the risk of this side effect. In this review, we discuss data on the risk of thromboembolic side effects, with special emphasis on the mechanism that may be responsible for this increased risk. Many indirect data indicate that higher thromboembolic risk may be related to the specificity of JAK inhibitor action, such that preferentially blocking one signaling pathway upsets the balance between pro and anti-thrombotic activities.Citation
Kotyla PJ, Engelmann M, Giemza-Stokłosa J, Wnuk B, Islam MA. (2021) Thromboembolic Adverse Drug Reactions in Janus Kinase (JAK) Inhibitors: Does the Inhibitor Specificity Play a Role? International Journal of Molecular Sciences. 22 (5), Article number 2449. https://doi.org/10.3390/ijms22052449Publisher
MDPI AGJournal
International Journal of Molecular SciencesPubMed ID
33671049 (pubmed)Additional Links
https://www.mdpi.com/1422-0067/22/5/2449Type
Journal articleLanguage
enDescription
© 2021 The Authors. Published by MDPI. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3390/ijms22052449ISSN
1661-6596EISSN
1422-0067Sponsors
This research received no external funding.ae974a485f413a2113503eed53cd6c53
10.3390/ijms22052449
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Except where otherwise noted, this item's license is described as Licence for published version: Creative Commons Attribution 4.0 International
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