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关键字:银屑病;JAK抑制剂

年  份:2019   点击量:115

文献摘要 全文翻译

Psoriasis is a prevalent chronic inflammatory disease. The inflammatory response is driven by T cells and mediated by multiple cytokines such as tumor necrosis factor and the interleukins IL-17 and IL-23. Moderate-to-severe psoriasis is treated systemically, using either biologics or conventional treatments with small-molecule drugs. The newer biologics are very effective and well tolerated, but not all patients respond to treatment with biologics, so there is a need for new treatment options for psoriasis. Janus kinase (JAK) inhibitors are a new drug class that may be of use in this respect. These inhibitors are already on the market for rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. They block the intracellular signal pathway mediated by JAK and signal transducer and activator of transcription (STAT) proteins, thereby inhibiting gene transcription of proinflammatory cytokines. JAK inhibitors are currently being tested as potential treatments for psoriasis. They have shown clinical efficacy as measured by the Psoriasis Area and Severity Index 75 response in both phase 2 and 3 trials, and appear to be well tolerated overall. This review provides an overview of the mechanisms underlying the actions of JAK inhibitors in psoriasis, together with the results of clinical trials testing their efficacies when used to treat the disease.

银屑病是一种常见的慢性炎症性疾病。炎症反应由T细胞驱动,并由多种细胞因子介导,如肿瘤坏死因子和白介素IL-17和IL-23。中度至重度银屑病采用生物制剂或常规小分子药物系统治疗。新型生物制剂非常有效且耐受性良好,但并非所有患者生物制剂治疗有效,因此有必要为银屑病患者提供新的治疗选择。Janus激酶(JAK)抑制剂是一种可用于治疗银屑病的新型药物。这些抑制剂已经在市场上用于治疗类风湿性关节炎、银屑病关节炎和溃疡性结肠炎。它们阻断JAK介导的细胞内信号通路,阻断信号转导因子和转录激活因子(STAT)蛋白,从而抑制促炎细胞因子的基因转录。目前正在测试JAK抑制剂作为治疗银屑病的潜在方法。在2期和3期试验中,通过银屑病面积和严重程度指数评分衡量其临床疗效,且总体上耐受性良好。本文综述了JAK抑制剂在银屑病治疗中的作用机制,以及临床试验结果。