Janus Kinase (JAK) Inhibitors in Rheumatoid Arthritis

Treatment of rheumatoid arthritis (RA) with biologic agents targeting inflammatory cytokines and cell surface molecules such as Tumor necrosis factor (TNF), Interleukin-6 (IL-6) and CTLA-4 has become a major focus in the field. Biologic agents are generally more effective than traditional disease-modifying antirheumatic drugs (DMARDs) when combined with MTX. However, not only about 30% of patients respond poorly to treatment but also the parenteral mode of administration and expenses are issues to be solved. Recently, a kinase inhibitor targeting Janus kinases (JAKs), has shown high efficacy on active RA in clinical trials. Among several JAK inhibitors under clinical trials for RA, tofacitinib (former CP690,550) which is highly specific for JAK3 is a step ahead for use in clinic. Kinase inhibitors are orally available, which is a major advantage over biologic agents, in addition to being less expensive than biologics. This review describes recent advances in JAK inhibitors for the treatment of RA and their possible mechanism of action. Keywords: Rheumatoid arthritis, Janus kinase, Kinase inhibitor, tacositinib, tofacitinib