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

    loading  Checking for direct PDF access through Ovid

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 ≤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.

Related Topics

    loading  Loading Related Articles