JAK3 and rheumatoid arthritis: Tofacitinib, an oral JAK inhibitor (jakinib), can inhibit differentisoforms of JAK, primarily JAK1 and JAK3.96 Utilization of tofacitinib in RA patients has reduced MMPs and interferon-relatedgenes in the synovium and reduced phosphorylation of STAT1 and STAT3,ultimately down-regulating IL-6 mediated signaling.97 Tofacitinib is the first FDA-approved jakinib for treatingRA.98 Other second-generation inhibitorsare also under clinical trials for the treatment of advanced RA.