Postgraduate School of Clinical Pharmacology and Toxicology, University of Milan, 20133 Milan, Italy.
Department of Clinical and Experimental Medicine, Rheumatology Unit, AOU "Gaetano Martino", University of Messina, 98100 Messina, Italy.
Biomolecules. 2020 Jul 5;10(7):1002. doi: 10.3390/biom10071002.
Janus kinase inhibitors (JAKi) belong to a new class of oral targeted disease-modifying drugs which have recently revolutionized the therapeutic panorama of rheumatoid arthritis (RA) and other immune-mediated diseases, placing alongside or even replacing conventional and biological drugs. JAKi are characterized by a novel mechanism of action, consisting of the intracellular interruption of the JAK-STAT pathway crucially involved in the immune response. The aim of this narrative review is to globally report the most relevant pharmacological features and clinical outcomes of the developed and incoming JAKi for RA, based on the available preclinical and clinical evidence. A total of 219 papers, including narrative and systematic reviews, randomized controlled trials (RCTs), observational studies, case reports, guidelines, and drug factsheets, were selected. The efficacy and safety profile of both the first generation JAKi (baricitinib and tofacitinib) and the second generation JAKi (upadacitinib, filgotinib, peficitinib, decernotinib and itacitinib) were compared and discussed. Results from RCTs and real-life data are encouraging and outline a rapid onset of the pharmacologic effects, which are maintained during the time. Their efficacy and safety profile are comparable or superior to those of biologic agents and JAKi proved to be efficacious when given as monotherapy. Finally, the manufacturing of JAKi is relatively easier and cheaper than that of biologics, thus increasing the number of compounds being formulated and tested for clinical use.
Janus 激酶抑制剂（JAKi）属于一类新型的口服靶向疾病修饰药物，最近彻底改变了类风湿关节炎（RA）和其他免疫介导性疾病的治疗前景，将传统药物和生物药物并列，甚至取代了它们。JAKi 的作用机制新颖，包括细胞内阻断 JAK-STAT 通路，该通路在免疫反应中至关重要。本综述的目的是根据现有临床前和临床证据，全面报告已开发和即将推出的 JAKi 治疗 RA 的最相关的药理学特征和临床结果。共选择了 219 篇论文，包括叙述性和系统评价、随机对照试验（RCT）、观察性研究、病例报告、指南和药物简介。第一代 JAKi（巴瑞替尼和托法替布）和第二代 JAKi（乌帕替尼、菲戈替尼、培非替尼、德塞替尼和伊替替尼）的疗效和安全性特征进行了比较和讨论。RCT 和真实世界数据的结果令人鼓舞，概述了药物作用的快速起效，并在整个治疗期间得以维持。其疗效和安全性与生物制剂相当或更优，并且在作为单药治疗时已被证明有效。最后，JAKi 的制造相对比生物制剂更容易且更便宜，因此增加了用于临床应用的化合物数量。
