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Effects of tofacitinib on lymphocytes in rheumatoid arthritis: relation to efficacy and infectious adverse events

Sonomoto K, Yamaoka K, Kubo S et al. - Rheumatology doi:10.1093/rheumatology/ket466

Due to its function as a JAK1/3 inhibitor, tofacitinib has effects on a wide ranging variety of cells. The authors of this paper have previously reported a suppression in cytokine production by CD4+ T lymphocytes caused by tofacitinib, while others have reported reduced chemokine production from fibroblast-like synoviocytes. The effects of tofacitinib on other cells however remain largely unknown. This study focused on tofacitinib’s effects on CD4+ T lymphocyte proliferation and on subsets of lymphocytes with an emphasis on how this relates to efficacy and infectious adverse events.
Forty-four patients with RA were treated with tofacitinib for 12 months. The mean SDAI score was 36.5 at the beginning of treatment, reduced to 6.2 but with no change in peripheral lymphocyte count or absolute number of CD4+ and CD8+ T lymphocytes. However, the proliferation of CD4+ T lymphocytes was suppressed which correlated with SDAI improvement but not with infectious AEs. A CD8+ count =211 per µl at baseline was a significant predictor of clinically significant infectious AEs.

Keywords: JAK, Tofacitinib, Preclinical, MOA

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Upload date: February 2014

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