Yamaoka Kunihiro, Maeshima Keisuke, Kubo Satoshi, Sonomoto Koshiro, Tanaka Yoshiya
The First Department of Internal Medicine, School of Medicine, University of Occupational and Enviromental Health, Japan.
Nihon Rinsho Meneki Gakkai Kaishi. 2012;35(2):112-7. doi: 10.2177/jsci.35.112.
Treatment of rheumatoid arthritis (RA) has dramatically developed with the use of biologics targeting inflammatory cytokines. However, expense and parenteral use can cause issues in the initiation and continuation of the treatment. Therefore a new orally available anti-rheumatic drug has been long-awaited. Recently, small-molecule compounds targeting Janus kinase (JAK) has shown clinical efficacy similar to biologics in clinical trials for active RA. Among the JAK-inhibitors, new drug application for tofacitinib is concurrently under review in western and asian countries and is highly expected to become a new anti-rheumatic drug in the near future. In order to evaluate the mode of action, we utilized peripheral blood and synovium from RA patients. Proliferation and cytokine production of CD4+ T cell was prominently reduced and subsequently inhibited cartilage destruction by the synovium. Our result is in line with the inhibitory effect of tofacitinib on joint destruction in RA patients those who were treated with tofacitinib. Therefore, further clinical efficacy is expected in the in the long-term treatment with tofacitinib.
随着针对炎性细胞因子的生物制剂的使用，类风湿关节炎（RA）的治疗有了显著进展。然而，费用和肠胃外给药方式可能会在治疗的起始和持续过程中引发问题。因此，一种新型口服抗风湿药物一直备受期待。最近，在活动性RA的临床试验中，靶向Janus激酶（JAK）的小分子化合物已显示出与生物制剂相似的临床疗效。在JAK抑制剂中，托法替布的新药申请正在西方国家和亚洲国家同时接受审查，并且有望在不久的将来成为一种新型抗风湿药物。为了评估其作用方式，我们使用了RA患者的外周血和滑膜。CD4+T细胞的增殖和细胞因子产生显著减少，随后滑膜对软骨破坏的抑制作用增强。我们的结果与托法替布对接受托法替布治疗的RA患者关节破坏的抑制作用一致。因此，预计托法替布的长期治疗会有进一步的临床疗效。
