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Review Article

类风湿关节炎的新治疗方法:Janus激酶抑制剂的作用

卷 26, 期 16, 2019

页: [2823 - 2843] 页: 21

弟呕挨: 10.2174/0929867325666180209145243

价格: $65

摘要

类风湿关节炎(RA)是一种以滑膜炎症和增生、自身抗体产生、软骨和骨骼破坏以及多种全身特征为特征的慢性炎症性疾病。心血管、肺、心理和肌肉受累是风湿性关节炎的主要共病，并与疾病的严重程度和长期预后有关。 风湿病的药物治疗在过去几年里有了显著的进展。此外，治疗目标的广泛采用和严格的控制策略导致了结果的显著改善，因此无药缓解是目前治疗风湿性关节炎的一个现实目标。然而，尽管有多种治疗选择，高达40%的患者对目前的治疗没有反应，包括生物制剂。小分子疗法为炎症性疾病的治疗提供了生物疗法之外的另一种选择。在过去的5年中，针对Janus激酶(JAKs)的小分子化合物已经被开发出来。由于jak对免疫细胞的细胞信号传导至关重要，尤其是控制对许多细胞因子的反应，因此jak抑制剂很快成为一种很有前途的口服疗法，在RA的治疗中被证明是有效的。Tofacitinib是首个被批准用于治疗RA的Janus Kinase (JAK)抑制剂，随后是baricitinib。其他几种JAK抑制剂目前正在进行II期和III期临床试验，用于治疗一种不同的自身免疫性疾病。这些化合物中的大多数具有与生物制剂相似的总体可接受安全性，其中感染是最常见的不良事件。除了托法替尼，其他JAK抑制剂的安全性数据仍然有限。长期随访和进一步的研究需要评估这些小分子的总体安全性和全球恶性肿瘤的风险，尽管迄今为止还没有明确的相关报道。在这里，我们将回顾JAK抑制剂的主要特点，包括其分子靶点的细节，以及迄今为止在RA治疗中获得的临床证据。

关键词: 类风湿性关节炎，janus激酶抑制剂，慢性疾病，炎症，无药缓解，增生

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