JAK inhibitors (JAKi): Mechanisms of action and perspectives in systemic and autoimmune diseases.

Abstract

Janus kinase (JAK) molecules are involved in important cellular activation pathways. Over the past decade, many targeted therapies have emerged, including the increasingly promising role of JAK inhibitors (JAKi) in the treatment of inflammatory and autoimmune diseases. The spectrum of use of these small molecules is increasingly broader. JAKi have been approved in several autoimmune diseases. Currently, four molecules (tofacitinib, baricitinib, upadacitinib and filgotinib) have been labeled for moderate to severe rheumatoid arthritis (RA) with failure or poor tolerance of one or more conventional disease-modifying antirheumatic drug (csDMARDS), or biologics (bDMARDS). JAKi are now also commonly used in other diseases such as psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis. They have also shown promising results in clinical trials for the treatment of other autoimmune conditions. We present here their mechanisms of action, and the main data about JAKi use on systemic and autoimmune diseases.