Clinical Aspects of Janus Kinase (JAK) Inhibitors in the Cardiovascular System in Patients with Rheumatoid Arthritis

Int J Mol Sci. 2020 Oct 7;21(19):7390. doi: 10.3390/ijms21197390.

Abstract

Janus kinase (JAK) inhibitors, a novel class of targeted synthetic disease-modifying antirheumatic drugs (DMARDs), have shown their safety and efficacy in rheumatoid arthritis (RA) and are being intensively tested in other autoimmune and inflammatory disorders. Targeting several cytokines with a single small compound leads to blocking the physiological response of hundreds of genes, thereby providing the background to stabilize the immune response. Unfortunately, blocking many cytokines with a single drug may also bring some negative consequences. In this review, we focused on the activity of JAK inhibitors in the cardiovascular system of patients with RA. Special emphasis was put on the modification of heart performance, progression of atherosclerosis, lipid profile disturbance, and risk of thromboembolic complications. We also discussed potential pathophysiological mechanisms that may be responsible for such JAK inhibitor-associated side effects.

Keywords: JAK/STAT; Janus kinase inhibitors; cardiovascular system; cytokines; heart failure; lipid profile disturbances; rheumatoid arthritis; thromboembolic.

Publication types

  • Review

MeSH terms

  • Animals
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / complications*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / etiology
  • Arthritis, Rheumatoid / metabolism
  • Autoimmunity / drug effects
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / metabolism
  • Cardiovascular System / drug effects*
  • Cardiovascular System / metabolism
  • Cytokines / metabolism
  • Disease Susceptibility
  • Humans
  • Immunity / drug effects
  • Inflammation Mediators / metabolism
  • Janus Kinase Inhibitors / administration & dosage
  • Janus Kinase Inhibitors / adverse effects*
  • Janus Kinase Inhibitors / therapeutic use
  • Janus Kinases / metabolism
  • Lipid Metabolism / drug effects
  • STAT Transcription Factors / metabolism

Substances

  • Antirheumatic Agents
  • Cytokines
  • Inflammation Mediators
  • Janus Kinase Inhibitors
  • STAT Transcription Factors
  • Janus Kinases