Rheumatoid arthritis is an autoimmune disease characterized by chronic joint inflammation. Patients who do not respond to firstline therapies can be treated with anti-cytokine therapies, but these large biologics must be administered parenterally. Two studies describe promising results from Phase III clinical trials in which patients with rheumatoid arthritis were treated orally with tofacitinib (Pfizer), a small-molecule inhibitor of Janus kinases (JAKs). Inhibition of JAK1 and JAK3 by tofacitinib blocks signalling by multiple cytokines that are important for lymphocyte function, including interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15 and IL-21. In both studies, patients treated with tofacitinib had improved clinical outcomes, and van Vollenhoven et al. found that tofacitinib was as effective as TNF blockade. On a cautionary note, the studies observed increased rates of infection and higher cholesterol levels in patients receiving tofacitinib. Both groups conclude that further trials are needed to evaluate the safety of this novel therapy.
ORIGINAL RESEARCH PAPERS
Fleischmann, R. et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N. Engl. J. Med. 367, 495–507 (2012)
van Vollenhoven, R. F. et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N. Engl. J. Med. 367, 508–519 (2012)
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Bordon, Y. JAK inhibitor effective in rheumatoid arthritis. Nat Rev Immunol 12, 621 (2012). https://doi.org/10.1038/nri3292
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DOI: https://doi.org/10.1038/nri3292