Tofacitinib: Current considerations in the management of immune inflammatory disorders

Tofacitinib, the first member of targeted-synthetic DMARDs, is an oral inhibitor of Janus kinases, preferentially JAK 1 and 3. It is an analogue of ATP and inhibits several pro-inflammatory cytokines and pathways. Tofacitinib is rapidly absorbed and eliminated mainly via liver. Efficacy of tofacitinib has been studied extensively in RA patients with different clinical scenarios. Now, tofacitinib is approved in several countries with the indications of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, polyarticular and systemic juvenile idiopathic arthritis and ulcerative colitis. Also, studies to assess efficacy of tofacitinib in patients with several different indications are under consideration. Neutropenia, anemia, elevation of transaminase levels, hyperlipidemia and increased risk of infections with several causes are well-known side effects. However, recent data from ORAL Surveillance study shed the light into the risk of cardiovascular events and malignancy. In that study, RA patients over 50 years with at least 1 cardiovascular risk factor were randomized to anti-TNFs or tofacitinib; revealing and increased cardiovascular event risk and malignancy (especially lung cancer and lymphoma) in tofacitinib arm. Although post hoc analysis of the data set suggested a possible link between history of cardiovascular disease and both cardiovascular and malignancy end-points, FDA and EMA announced black-box warnings for all JAK inhibitors covering all indications. Obviously JAK inhibitors, the game changers of the last decade, need further evaluation especially regarding safety issues.