Publications

This article focuses on the development of new small molecular inhibitors of Janus kinases (Jaks) in clinical trials for rheumatoid arthritis (RA). Of these, tofacitinib is at the most advanced stage of its clinical development and this article includes an overview of the results from the main tofacitinib clinical trials to date. These include the ORAL-Start study in methotrexate (MTX)-naïve patients; ORAL-Scan in inadequate responders to MTX; ORAL-Solo and ORAL-Sync in inadequate responders to non-biologic or biologic disease modifying antirheumatic drugs (DMARDs); ORAL-Standard in inadequate responders to MTX; and ORAL-Step in inadequate responders to tumour necrosis factor inhibitors (TNFi). Safety data from the phase 2 to phase 3 development programme and long-term extension studies of tofacitinib are also discussed. The article ends by describing the results from early clinical trials of other Jak inhibitors such as VX-509 (Vertex), which has selectivity for Jak3; LY3009104 (baricitinib), which has selectivity for Jak1 and Jak2; and GLPG0634 (Galapagos), which has selectivity for Jak1.