International Journal of Clinical Rheumatology June 2013; 8(3):311–13The tofacitinib ORAL research program involves six phase 3 trials (Standard, Solo, Step, Scan, Sync and Start) to assess the safety and efficacy of tofacitinib 5 and 10 mg twice daily as monotherapy, or with either background MTX or traditional DMARD therapy. This report by Salgado et al. provides an overall analysis of the each of the study designs and the clinical results to date. The results show that tofacitinib effectively controlled the signs and symptoms of RA across a range of patient populations including patients’ naïve to MTX, and in those with an inadequate response to MTX; TNFi; or at least one non-biologic or biologic DMARD. Tofacitinib was also shown to improve physical function and halt the progression of joint damage (by radiographic assessment). Upper respiratory tract infection, headache, diarrhoea and nasopharyngitis were common adverse events. A dose-dependent increase in LDL cholesterol levels and a reduction in neutrophil counts were associated with tofacitinib treatment but were similar to those seen with the TNFi monoclonal antibody, adalimumab in ORAL Standard. There may be implications from these dose-related adverse events that may limit up-titration of tofacitinib, and this possible repercussion is discussed in more depth. The report concludes that tofacitinib is effective and that long-term safety data, and comparisons with other DMARDs and JAK inhibitors may also be necessary to determine the role of tofacitinib in the treatment of RA.