A comparison of Janus kinase inhibitor safety in rheumatoid arthritis

Abstract

The last decade has seen considerable advancement in the treatment options available to patients with rheumatoid arthritis (RA) through the development of oral, small molecules that target and inhibit Janus kinases (JAKi). These drugs have a rapid onset of action, disrupting the Janus kinase/signal transducer and activator of transcription pathway and preventing the production of cytokines involved in inflammatory processes. They have the potential to provide immunomodulatory benefits across a broad range of diseases. This narrative review focuses on the safety profile of tofacitinib, baricitinib, upadacitinib, and filgotinib. Although JAKi have been shown to be effective in the treatment of RA, it is posited that they have different selectivities, which are likely to affect their safety profiles in RA patients. Currently, there are limited long‐term safety data available, with most data coming from randomized controlled trials. However, the data that are available show that upadacitinib and filgotinib may have improved safety profiles. This is particularly true in relation to herpes zoster, venous thromboembolism, and gastrointestinal perforation. Future research is needed to investigate the safety and efficacy of switching between JAKi when a previous JAKi has not been tolerated or has been ineffective.

After JAK inhibitor failure: to cycle or to switch, that is the question – data from the JAK-pot collaboration of registries

“…On the other hand, available JAKis differ in terms of affinity for the receptor-associated tyrosine kinases of the JAK family. Tofacitinib is a selective inhibitor of JAK1 and JAK3, while baricitinib is a selective inhibitor of JAK1 and JAK2, and upadacitinib and filgotinib inhibit JAK1 selectively 18. Although there is no evidence that differences in affinity influence response to JAKi, based on previous experience with cycling of TNFi, a second JAKi is often used in case of failure to the first JAKi.…”

Upadacitinib and Cardiovascular Adverse Events in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

“…As the treatment landscape for rheumatoid arthritis evolves, the introduction of Janus kinase inhibitors, such as Upadacitinib, has promised enhanced symptom management and improved quality of life for patients [6][7][8]. Nevertheless, the emergence of cardiovascular adverse events as a potential side effect of JAK inhibitors has raised crucial questions about their overall safety profile [9][10][11][12][13]. Indeed, while some studies have examined the safety profile of Upadacitinib, there is a recognized need for a comprehensive and up-todate investigation [14][15][16].…”