Targeting the Janus kinases in rheumatoid arthritis: focus on tofacitinib

Treatment of rheumatoid arthritis (RA) has markedly advanced by the advent of biologic disease-modifying antirheumatic drugs (DMARDs). However, they require special storage and transportation and remission is observed in ∼ 30%. Tofacitinib inhibits the nonreceptor tyrosine kinase family Janus kinase (JAK), which is activated immediately after cytokines bind to their receptor within the cytoplasmic membrane.

Tofacitinib is an orally available tablet and treatment efficacy is similar to biologic DMARDs. Pharmacokinetics, and drug-drug interaction is covered in this article. In addition, efficacy and adverse events from the Phase II and Phase III are overviewed. Additionally, the authors have described the novel mechanism of action (MOA) of tofacitinib in relevance to efficacy and adverse events. Because of its MOA, greater caution is necessary for selecting appropriate patients for treatment initiation and further treatment continuation following clinical trials.

Tofacitinib is a new class of DMARDs orally available with a new mechanism of action and with strong clinical efficacy similar to biologic DMARDs. Multiple cytokines and signaling pathways are partially inhibited at clinical doses that are in contrast to biological DMARDs. Further investigation is necessary to come to a conclusion on risk-benefit ratio and selection of patients.