The lowdown: On 6 November, tofacitinib (Xeljanz; Pfizer) was approved by the US Food and Drug Administration (FDA) for adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate, the standard oral DMARD. This success is one culmination of research efforts investigating the immunomodulatory potential of JAK inhibitors, since the discovery in the 1990s of the pivotal role that JAKs have in cytokine signalling pathways. Tofacitinib (previously known as tasocitinib and CP-690550) was first reported in 2003 as a JAK3 inhibitor, and has been at the forefront of a new wave of oral DMARDs for some time (Nature Rev. Drug Discov. 9, 257–258; 2010).
Tofacitinib received backing from an FDA advisory panel in May, based on five successful Phase III trials, although concerns were raised about the risks of infection, and additional data analysis requested by the FDA pushed back its original prescription drug user fee act (PDUFA) date of 21 August by 3 months. It was approved 15 days ahead of the new PDUFA date, with a risk evaluation and mitigation strategy (REMS) and a black box warning highlighting the increased risk of infections, cancers and lymphoma. The FDA has also required that Pfizer conducts long-term post-marketing studies to evaluate these risks.
