Vnitr Lek 2023, 69(3):181-188 | DOI: 10.36290/vnl.2023.031

JAK inhibition in the treatment of inflammatory rheumatic diseases

Ladislav Šenolt

Revmatologický ústav 1. LF UK, Praha

The most common immune-mediated inflammatory rheumatic diseases, such as rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis, have reached significant progress in recent years with the introduction of biological therapies targeting cytokines and immune cells, but also small molecules targeting intracellular enzymes, specifically Janus kinases (JAKs). Intracellular JAK signaling is activated by binding various cytokines or growth factors to their respective cellular receptors, leading to the activation of Signal Transducers and Activators of Transcription (STAT) and ultimately gene transcription with a pivotal role in innate and adaptive immune responses. Four Janus kinases have been described: JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2). Currently, four JAK inhibitors (tofacitinib, baricitinib, upadacitinib, and filgotinib) are approved for the treatment of rheumatoid arthritis, some for psoriatic arthritis and axial spondyloarthritis as well. JAK inhibitors exhibit varying selectivity against individual kinases. Certain JAK inhibitors are being investigated for other rarer connective tissue diseases. A general advantage of JAK inhibitors is their oral administration, rapid onset of action, and efficacy in monotherapy. The safety profile of JAK inhibitors compared to biological therapies appears to be comparable, with a higher incidence of herpes zoster and discussions about increased occurrence of serious cardiovascular diseases, thromboembolic complications, and malignancies in high-risk patients. The aim of this work is to summarize the latest findings on JAK inhibitors in approved indications for the most common rheumatic diseases.

Keywords: immune‑mediated inflammatory rheumatic diseases, JAK inhibitors, intracellular signalling, safety profile.

Accepted: April 27, 2023; Published: May 16, 2023  Show citation