Adverse events, clinical considerations and management recommendations in rheumatoid arthritis patients treated with JAK inhibitors

Expert Rev Clin Immunol. 2018 Nov;14(11):945-956. doi: 10.1080/1744666X.2018.1504678. Epub 2018 Aug 21.

Abstract

A new class of oral synthetic drugs has been developed for the treatment of rheumatoid arthritis (RA) with the aim of blocking the Janus kinase/signal transducer and activator of transcription (JAK-STAT) system. Tofacitinib and baricitinib have been approved for the treatment RA patients who inadequately respond to methotrexate or anti-tumor necrosis factor drugs. The aim of this narrative review is to summarize the data concerning the drugs' basic mechanisms and clinical trial results in order to inform clinicians about the serious and non-serious adverse events associated with JAK inhibitors. Areas covered: The mechanisms, adverse events, and clinical trial data associated with the use of JAK inhibitors in RA patients were reviewed by searching the PubMed, Medline, and Cochrane Library databases for papers published between 1999 and April 2018 using combinations of words or terms. Articles not written in English were excluded. Expert commentary: Management of the adverse events of JAK inhibitors is challenging because of the lack of robust treatment data used and the heterogeneity of the events themselves. Treatment decisions are often made clinically on the basis of age and the burden of comorbidities, and require the multidisciplinary collaboration of rheumatologists and other specialists.

Keywords: JAK inhibitors; baricitinib; rheumatoid arthritis; small molecules; tofacitinib.

Publication types

  • Review

MeSH terms

  • Animals
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Azetidines / pharmacology
  • Azetidines / therapeutic use*
  • Clinical Trials as Topic
  • Humans
  • Janus Kinase 1 / antagonists & inhibitors
  • Piperidines / pharmacology
  • Piperidines / therapeutic use*
  • Purines
  • Pyrazoles
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*
  • Pyrroles / pharmacology
  • Pyrroles / therapeutic use*
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use*

Substances

  • Antirheumatic Agents
  • Azetidines
  • Piperidines
  • Purines
  • Pyrazoles
  • Pyrimidines
  • Pyrroles
  • Sulfonamides
  • tofacitinib
  • Janus Kinase 1
  • baricitinib