This advance took on additional clinical significance which eventually resulted in the development of two JAK-selective small molecule inhibitors (SMIs), namely tofacitinib (JAK3) and ruxolitinib (JAK1/JAK2) [25,26,27,28], and especially tofacitinib, which has become part of the overall RA drug armamentarium. This evidence concerns the gene JAK2 and rheumatoid arthritis.