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


CONCLUSIONS
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.
First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555, Japan. tanaka@med.uoeh-u.ac.jp.
Koshiro
K
Sonomoto
Kunihiro
K
Yamaoka
Satoshi
S
Kubo
Shintaro
S
Hirata
Shunsuke
S
Fukuyo
Keisuke
K
Maeshima
Katsunori
K
Suzuki
Kazuyoshi
K
Saito
Yoshiya
Y
Tanaka
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007239:Infections / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome
D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib
Janus kinase inhibitor; T lymphocytes; rheumatoid arthritis; tofacitinib