Thromboembolic adverse drug reactions in janus kinase (Jak) inhibitors: Does the inhibitor specificity play a role?

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/ijms22052449

PubMed ID

33671049 (pubmed)

Additional Links

https://www.mdpi.com/1422-0067/22/5/2449

Type

Journal article

Language

en

Description

© 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/ijms22052449

ISSN

1661-6596

EISSN

1422-0067

Rights

Licence for published version: Creative Commons Attribution 4.0 International

cb

Collections

Faculty of Science and Engineering