Emerging protein kinase inhibitors for the treatment of rheumatoid arthritis

Expert Opin Emerg Drugs. 2021 Sep;26(3):303-321. doi: 10.1080/14728214.2021.1964472. Epub 2021 Aug 16.

Abstract

Introduction: Protein tyrosine kinase inhibitors are emergent drugs in the treatment of rheumatoid arthritis (RA); they block the signal transduction in immune cells preventing the production and release of pro-inflammatory cytokines.

Areas covered: The current research aims to review the role of Janus, Bruton's and spleen kinase inhibitors for the treatment of RA. Mechanism of action, rationale for usage, and the main efficacy and safety outcomes in phase II and III clinical trials are described.

Expert opinion: In RA, the development of Bruton kinase inhibitors was interrupted because they failed to demonstrate superiority versus placebo. The spleen kinase inhibitors had their development deprioritized because their risk/benefit profile was unfavorable compared to janus kinase inhibitors (JAKi). JAKi proved to be effective in treatment naïve patients and in those with previous failure to methotrexate and/or biological therapy. There still remain important points about JAKi that need more studies: the clinical importance of JAKi selectivity should be further evaluated in head-to-head trials and the safety profile of JAKi, mainly regarding the risk of malignancy and thromboembolic events, must be analyzed in long-term real-life studies.

Keywords: Arthritis; Bruton kinase inhibitors; drug evaluation; janus kinase inhibitors; protein kinase inhibitors; rheumatoid; spleen kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Antirheumatic Agents* / adverse effects
  • Arthritis, Rheumatoid* / drug therapy
  • Humans
  • Janus Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors / adverse effects

Substances

  • Antirheumatic Agents
  • Janus Kinase Inhibitors
  • Protein Kinase Inhibitors