The emerging safety profile of JAK inhibitors in rheumatic disease

Nat Rev Rheumatol. 2017 Apr;13(4):234-243. doi: 10.1038/nrrheum.2017.23. Epub 2017 Mar 2.

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.

Publication types

  • Review

MeSH terms

  • Azetidines / adverse effects*
  • Azetidines / therapeutic use
  • Humans
  • Infections / chemically induced*
  • Janus Kinases / antagonists & inhibitors*
  • Neoplasms / chemically induced*
  • Piperidines / adverse effects*
  • Piperidines / therapeutic use
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines / adverse effects*
  • Pyrimidines / therapeutic use
  • Pyrroles / adverse effects*
  • Pyrroles / therapeutic use
  • Rheumatic Diseases / drug therapy*
  • Signal Transduction
  • Sulfonamides / adverse effects*
  • Sulfonamides / therapeutic use

Substances

  • Azetidines
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrroles
  • Sulfonamides
  • tofacitinib
  • Janus Kinases
  • baricitinib