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The emerging safety profile of JAK inhibitors in rheumatic disease

Nature Reviews Rheumatology volume 13, pages 234–243 (2017)Cite this article

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A Corrigendum to this article was published on 31 March 2017

This article has been updated

Key Points

  • Despite differences in selectivity between Janus kinase (JAK) inhibitors, a large overlap exists in their safety profiles

  • All JAK inhibitors have been associated with a decrease in neutrophil number, although changes in numbers of lymphocytes and natural killer cells vary between compounds

  • An increased risk of viral infections (particularly herpes zoster) seems to distinguish the safety profile of tofacitinib from that of biologic DMARDs

  • Similarly to tofacitinib, other JAK inhibitors also seem to increase the risk of herpes zoster infection despite differences in JAK selectivity

  • To date, no increased risk of malignancy has been reported with tofacitinib in rheumatoid arthritis; however, experience is limited and this risk must be evaluated in the long term with all JAK inhibitors

  • The prevention of herpes zoster and other opportunistic infections is both feasible and important in the setting of JAK inhibition for the treatment of autoimmune inflammatory diseases

Abstract

Tofacitinib is the first Janus kinase (JAK) inhibitor commercially approved for the treatment of rheumatoid arthritis. This compound and a number of other JAK inhibitors are currently being tested in phase II and III trials for the treatment of a variety of autoimmune inflammatory diseases. Whereas a characteristic safety profile is emerging for some JAK inhibitors, differences between individual agents might emerge on the basis of distinct potency against their molecular targets. Similarly to biological therapy, JAK inhibition can lead to serious and opportunistic infections, and viral infections seem to be particularly frequent. Although no malignancy signals have been identified to date, long-term follow-up and further research are needed to understand the risk of malignancy associated with these compounds. As is the case for biologic agents, vaccination is important to mitigate the risks of these emerging therapies.

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Figure 1: Overview of JAK–STAT signalling in host defense and cellular homeostasis.

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Change history

  • 31 March 2017

    In 'Gastrointestinal perforation' of the 'Adverse effects of JAK inhibitors' section, in the sentence “In patients with RA receiving baricitinib, two cases of gastrointestinal perforations were reported (an incidence of 5 cases per 1,000 patient-years in the development program)” the incidence should have been 0.5 cases per 1,000 patient-years. This error has been corrected in the online version of the article.

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    Kevin L. Winthrop

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Winthrop, K. The emerging safety profile of JAK inhibitors in rheumatic disease. Nat Rev Rheumatol 13, 234–243 (2017). https://doi.org/10.1038/nrrheum.2017.23

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