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

Koshiro Sonomoto, Kunihiro Yamaoka, Satoshi Kubo, Shintaro Hirata, Shunsuke Fukuyo, Keisuke Maeshima, Katsunori Suzuki, Kazuyoshi Saito, Yoshiya Tanaka

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24 Citations (Scopus)

Abstract

Objectives: To assess the effects of tofacitinib on T lymphocytes in RA patients with a special focus on efficacy and infectious adverse events (iAEs). Methods: Forty-four RA patients participated in 12-month phase II/III randomized clinical trials and an open-label extension trial. Peripheral lymphocyte subsets and in vitro CD4+ T lymphocyte proliferation were measured in 23 patients of 44 at baseline and at the end of the 12-month trial. Results: Forty-four patients [35 females, age 54.3 years, disease duration 84.3 months, simplified disease activity index (SDAI) 36.5, CRP 24.9 mg/l, ESR 53 mm/h, MMP-3 284 pg/ml, RF 172.6 IU/ml, neutrophil count 4842 per μl, lymphocyte count 1410 per μl] were treated with tofacitinib. At the end of the study, the SDAI improved to 6.2, but the peripheral lymphocyte count and absolute numbers of CD4+ and CD8+ subpopulations did not change during this period. However, CD4+ T lymphocyte proliferation was suppressed, which correlated with the improvement in SDAI, but not with iAEs (n = 19) during the 12-month treatment. Receiver operating characteristic analysis identified a CD8+ T lymphocyte count le;211 per μl at baseline as a significant predictor of clinically significant iAEs. Conclusion: The efficacy of tofacitinib is mediated through the suppression of CD4+ T lymphocyte proliferation without affecting the absolute number of these cells in the periphery. A low CD8+ T cell count at baseline correlated with the development of iAEs during the treatment of RA patients.

Original languageEnglish
Article numberket466
Pages (from-to)914-918
Number of pages5
JournalRheumatology (United Kingdom)
Volume53
Issue number5
DOIs
Publication statusPublished - 2014 May

Keywords

  • Janus kinase inhibitor
  • Rheumatoid arthritis
  • T lymphocytes
  • Tofacitinib

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

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    Sonomoto, K., Yamaoka, K., Kubo, S., Hirata, S., Fukuyo, S., Maeshima, K., Suzuki, K., Saito, K., & Tanaka, Y. (2014). Effects of tofacitinib on lymphocytes in rheumatoid arthritis: Relation to efficacy and infectious adverse events. Rheumatology (United Kingdom), 53(5), 914-918. [ket466]. https://doi.org/10.1093/rheumatology/ket466