Abteilung Für Rheumatologie, Medizinische Universitat Wien Universitatsklinik Fur Innere Medizin III, Wien, Austria
Medicine 3, Division of Rheumatology, Medizinische Universitat Wien, Wien, Austria.
RMD Open. 2020 Nov;6(3). doi: 10.1136/rmdopen-2020-001374.
Review of efficacy and safety of Janus kinase (JAK) inhibition in immune-mediated inflammatory diseases (IMIDs).
A systematic literature research (SLR) of all publications on JAK inhibitors (JAKi) treatment published until March 2019 using MEDLINE, EMBASE and the Cochrane Library. Efficacy and safety were assessed in randomised controlled trials (RCTs), integrating long-term extension periods additionally for safety evaluation.
3454 abstracts were screened with 85 included in the final analysis (efficacy and RCT safety: n=72; safety only: n=13). Efficacy of RCTs investigating tofacitinib (TOFA, n=27), baricitinib (BARI, n=9), upadacitinib (UPA, n=14), filgotinib (FILGO, n=7), decernotinib (DEC, n=3) and peficitinib (PEF, n=7) was evaluated. Six head-to-head trials comparing JAKi with tumour necrosis factor inhibitors (TNFi) were included. Efficacy of JAKi was shown in rheumatoid arthritis (RA) for all agents, psoriatic arthritis (TOFA, FILGO), ankylosing spondylitis (TOFA, FILGO), systemic lupus erythematosus (BARI), chronic plaque psoriasis (TOFA, BARI, PEF), ulcerative colitis (TOFA, UPA), Crohn's disease (UPA, FILGO) and atopic dermatitis (TOFA, BARI, UPA). Safety analysis of 72 RCTs, one cohort study and 12 articles on long-term extension studies showed increased risks for infections, especially herpes zoster, serious infections and numerically higher rates of venous thromboembolic events. No increased malignancy rates or major adverse cardiac events were observed.
JAKi provide good efficacy compared to placebo (and to TNFi in RA and Pso) across various IMIDs with an acceptable safety profile. This SLR informed the task force on points to consider for the treatment of IMIDs with JAKi with the available evidence.
综述 Janus 激酶（JAK）抑制剂在免疫介导的炎症性疾病（IMIDs）中的疗效和安全性。
对截至 2019 年 3 月所有关于 JAK 抑制剂（JAKi）治疗的出版物进行系统文献检索（SLR），检索 MEDLINE、EMBASE 和 Cochrane 图书馆。在随机对照试验（RCT）中评估疗效和安全性，将长期扩展期纳入安全性评估。
筛选了 3454 篇摘要，最终纳入 85 篇进行分析（疗效和 RCT 安全性：n=72；安全性：n=13）。评估了托法替尼（TOFA，n=27）、巴瑞替尼（BARI，n=9）、乌帕替尼（UPA，n=14）、菲戈替尼（FILGO，n=7）、德塞替尼（DEC，n=3）和培非替尼（PEF，n=7）的 RCT 研究结果。纳入了 6 项比较 JAKi 与肿瘤坏死因子抑制剂（TNFi）的头对头试验。所有药物在类风湿关节炎（RA）、银屑病关节炎（TOFA、FILGO）、强直性脊柱炎（TOFA、FILGO）、系统性红斑狼疮（BARI）、慢性斑块状银屑病（TOFA、BARI、PEF）、溃疡性结肠炎（TOFA、UPA）、克罗恩病（UPA、FILGO）和特应性皮炎（TOFA、BARI、UPA）中均显示出疗效。对 72 项 RCT、1 项队列研究和 12 项长期扩展研究的安全性分析显示，感染风险增加，尤其是带状疱疹、严重感染，静脉血栓栓塞事件发生率略高。未观察到恶性肿瘤或重大心血管不良事件发生率增加。
JAKi 在各种 IMIDs 中与安慰剂（和 RA 中的 TNFi 和 Pso）相比具有良好的疗效，安全性可接受。本 SLR 为 JAKi 治疗 IMIDs 的工作组提供了治疗考虑因素和现有证据。
