Clinical utility of the oral JAK inhibitor tofacitinib in the treatment of rheumatoid arthritis.
Clinical utility of the oral JAK inhibitor tofacitinib in the treatment of rheumatoid arthritis.
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DOI：
10.2147/jir.s35901
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发表时间：
2013-11-15
影响因子：
4.5
通讯作者：
Meroni M
中科院分区：
文献类型：
--
作者：
Cutolo M;Meroni M
免疫/炎症细胞通过合成几种炎症介质（包括启动细胞内信号传导的细胞因子）在类风湿性关节炎（RA）患者中发挥作用。最近，已经测试了影响细胞内途径的转导和转录信号的小分子抑制剂（例如酪氨酸激酶的Janus激酶[JAK]家族）用于RA治疗。JAK家族有四个成员：JAK 1、JAK 2、JAK 3和TyK 2。JAK 1/JAK 3组成型结合细胞因子受体的细胞质部分-共同的γ链-其代表参与T细胞和自然杀伤细胞发育以及B细胞活化的几种细胞因子的共同亚基。托法替尼是一种口服JAK抑制剂，现已上市并有效治疗RA，多项II期和III期临床试验均显示了这一点。然而，长期安全性数据以及与其他疾病缓解抗风湿药物和小分子抑制剂的比较对于更好地确定托法替尼在RA中的作用是必要的。
Immune/inflammatory cells act in rheumatoid arthritis (RA)-affected patients by synthesizing several inflammatory mediators, including cytokines that initiate intracellular signaling. Recently, small molecule inhibitors of transduction and transcription signals that influence the intracellular pathways (such as the Janus kinase [JAK] family of tyrosine kinases) have been tested for RA treatment. Four members of the JAK family are known: JAK1, JAK2, JAK3, and TyK2. JAK1/JAK3 constitutively binds to the cytoplasmic portion of the cytokine receptor – the common gamma chain – that represents a common subunit of several cytokines involved in T-cell and natural killer cell development, as well as in B-cell activation. Tofacitinib is an oral JAK inhibitor that is now available and effective in RA treatment, as shown in multiple Phase II and Phase III clinical trials. However, long-term safety data and comparisons with other disease-modifying antirheumatic drugs and small molecule inhibitors are necessary to better determine the role of tofacitinib in RA.