JAK-STAT inhibitors: Immersing therapeutic approach for management of rheumatoid arthritis

Int Immunopharmacol. 2020 Sep:86:106731. doi: 10.1016/j.intimp.2020.106731. Epub 2020 Jun 23.

Abstract

Rheumatoid arthritis is a world leading cause of musculoskeletal disease. With the introduction of biological agents as treatment alternatives the clinical possibilities have grown exponentially. Currently most common Disease-modifying anti-rheumatic drugs (DMARDs) treatment option involves intravenous or subcutaneous injection, and some patients struggle to respond to DMARDs or lose their primary reaction. An oral drug formulation with lowered costs of manufacturing and flexibility for healthcare workers to preferably perform treatment will result in decreased healthcare expenditures and increased medication compliance. The JAK-STAT inhibitors, a new class of small molecules drugs, fulfills these criteria and has recently shown efficacy in rheumatoid arthritis. Here we give a summary of how JAK-STAT inhibitors function and a detailed review of current clinical trials. Convincing clinical results suggest that therapeutic inhibition of the JAK proteins can effectively modulate a complex cytokine-driven inflammation.

Keywords: JAK proteins; JAK-STAT; JAK-STAT inhibitors; Janus kinase pathway; Rheumatoid arthritis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Azetidines / therapeutic use
  • Clinical Trials as Topic
  • Cytokines / metabolism
  • Humans
  • Inflammation / drug therapy*
  • Janus Kinase Inhibitors / therapeutic use*
  • Janus Kinases / metabolism*
  • Protein Kinase Inhibitors / therapeutic use*
  • Purines / therapeutic use
  • Pyrazoles / therapeutic use
  • Pyridines / therapeutic use
  • STAT Transcription Factors / metabolism*
  • Signal Transduction / drug effects
  • Sulfonamides / therapeutic use
  • Triazoles / therapeutic use

Substances

  • Antirheumatic Agents
  • Azetidines
  • Cytokines
  • GLPG0634
  • Janus Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Purines
  • Pyrazoles
  • Pyridines
  • STAT Transcription Factors
  • Sulfonamides
  • Triazoles
  • Janus Kinases
  • baricitinib