Perspectives on JAK inhibitors in rheumatic diseases

Abstract

Rheumatoid arthritis is a systemic autoimmune disease with persistent inflammation primarily characterized by synovitis and joint destruction. Because joint damage progresses rapidly after onset, resulting in irreversible physical dysfunction and deformation of the affected joints, proper diagnosis and treatment are required from the early stages of the disease. The standard treatment of rheumatoid arthritis should be initiated by methotrexate if it is not contraindicated. However, in patients with inadequate responses to methotrexate, the addition of biological DMARDs or Janus kinase（JAK）inhibitors is recommended. The JAK proteins and STAT transcription factors mediate intracellular signal transduction at the downstream of cytokine receptors, which are implicated in the pathological processes of rheumatic diseases. JAK inhibitors, including tofacitinib, baricitinib, peficitinib, upadacitinib and filgotinib, are used for the treatment of rheumatoid arthritis and differ in their selectivity for different JAK isoforms. Although they are orally administered drugs, they have multi-target effects based on the inhibition of intracellular signaling and exert clinical effects just as promptly and strongly as biological DMARDs. JAK inhibitors should not be used without careful consideration as they are orally administered drugs with multi-target effects. Screening of risk factors and the indication before their use and monitoring adverse events during the treatment should be strictly performed for infection, cardiovascular disorders, thrombosis, malignancies and many.