Yamaoka Kunihiro
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Drug Saf. 2016 Sep;39(9):823-40. doi: 10.1007/s40264-016-0430-0.
The biologics have revolutionized the treatment of rheumatoid arthritis (RA). However, there are still patients that are difficult to control and a cure is still not achievable. Tofacitinib, a Janus kinase (JAK) inhibitor is an orally available, new-in-class, disease-modifying anti-rheumatic drug with similar efficacy to biologics. JAK is activated by multiple cytokines involved in the pathology of RA, and affects non-immune and immune cells, mainly the lymphocytes. Besides its anti-rheumatic effect, the recent focus has been on adverse events. As with other biologics, serious infections have been observed especially with patients with lymphopenia, consistent with the mechanism of action. The major difference in adverse events from other disease-modifying anti-rheumatic drugs is the prominent increase in the occurrence of herpes zoster; it is increased worldwide, especially in Asia. There are other concerns such as malignancies and hyperlipidemia that may cause cardiovascular events that deserve further attention. The first JAK inhibitor for RA is demonstrating great benefit along with some risk, providing insights into the post-biologic era.
生物制剂彻底改变了类风湿关节炎(RA)的治疗方式。然而,仍有一些患者难以得到有效控制,且目前仍无法治愈。托法替布是一种Janus激酶(JAK)抑制剂,是一种口服的新型疾病改善抗风湿药物,其疗效与生物制剂相似。JAK可被多种参与RA病理过程的细胞因子激活,并影响非免疫细胞和免疫细胞,主要是淋巴细胞。除了其抗风湿作用外,近期人们关注的焦点在于不良事件。与其他生物制剂一样,尤其在淋巴细胞减少的患者中观察到了严重感染,这与作用机制相符。与其他疾病改善抗风湿药物相比,不良事件的主要差异在于带状疱疹的发生率显著增加;在全球范围内,尤其是在亚洲,其发生率都有所上升。还有其他一些问题,如可能导致心血管事件的恶性肿瘤和高脂血症,值得进一步关注。首个用于RA的JAK抑制剂在带来巨大益处的同时也存在一定风险,为生物制剂时代之后的治疗提供了思路。