Rheumatoid arthritis (RA) is a representative autoimmune disease characterized 
by chronic and destructive inflammatory synovitis. The multiple cytokines play 
pivotal roles in RA pathogenesis by inducing intracellular signaling, and 
members of the Janus kinase (JAK) family are essential for such signal 
transduction. An orally available JAK3 inhibitor, tofacitinib, has been applied 
for RA, with satisfactory effects and acceptable safety in multiple clinical 
examinations. From phase 2 dose-finding studies, tofacitinib 5 mg and 10 mg 
twice a day appear suitable for further evaluation. Subsequently, multiple phase 
3 studies were carried out, and tofacitinib with or without methotrexate (MTX) 
is efficacious and has a manageable safety profile in active RA patients who are 
MTX naïve or show inadequate response to methotrexate (MTX-IR), 
disease-modifying antirheumatic drugs (DMARD)-IR, or tumor necrosis factor 
(TNF)-inhibitor-IR. The common adverse events were infections, such as 
nasopharyngitis; increases in cholesterol, transaminase, and creatinine; and 
decreases in neutrophil counts. Although the mode of action of tofacitinib 
remains unclear, we clarified that the inhibitory effects of tofacitinib could 
be mediated through suppression of interleukin (IL)-17 and interferon (IFN)-γ 
production and proliferation of CD4(+) T cells in the inflamed synovium. Taken 
together, an orally available kinase inhibitor tofacitinib targeting 
JAK-mediated signals would be expected to be a new option for RA treatment.