Rheumatology Service,Hospital De Clínicas De Porto Alegre. Rio Grande Do Sul, Brazil.
Expert Opin Emerg Drugs. 2021 Sep;26(3):303-321. doi: 10.1080/14728214.2021.1964472. Epub 2021 Aug 16.
Protein tyrosine kinase inhibitors are emergent drugs in the treatment of rheumatoid arthritis (RA); they block the signal transduction in immune cells preventing the production and release of pro-inflammatory cytokines.
The current research aims to review the role of Janus, Bruton's and spleen kinase inhibitors for the treatment of RA. Mechanism of action, rationale for usage, and the main efficacy and safety outcomes in phase II and III clinical trials are described.
In RA, the development of Bruton kinase inhibitors was interrupted because they failed to demonstrate superiority versus placebo. The spleen kinase inhibitors had their development deprioritized because their risk/benefit profile was unfavorable compared to janus kinase inhibitors (JAKi). JAKi proved to be effective in treatment naïve patients and in those with previous failure to methotrexate and/or biological therapy. There still remain important points about JAKi that need more studies: the clinical importance of JAKi selectivity should be further evaluated in head-to-head trials and the safety profile of JAKi, mainly regarding the risk of malignancy and thromboembolic events, must be analyzed in long-term real-life studies.
蛋白酪氨酸激酶抑制剂是治疗类风湿关节炎（RA）的新兴药物；它们阻断免疫细胞中的信号转导，防止促炎细胞因子的产生和释放。
目前的研究旨在综述 Janus、布鲁顿酪氨酸激酶抑制剂治疗 RA 的作用。描述了作用机制、使用理由以及 II 期和 III 期临床试验中的主要疗效和安全性结果。
在 RA 中，由于 Bruton 激酶抑制剂未能优于安慰剂，其开发被中断。与 Janus 激酶抑制剂（JAKi）相比，脾激酶抑制剂的风险/收益比不利，因此其开发被优先考虑。JAKi 已被证明在治疗初治患者和甲氨蝶呤和/或生物治疗失败的患者中有效。JAKi 仍有一些重要的问题需要更多的研究：在头对头试验中应进一步评估 JAKi 选择性的临床重要性，在长期真实世界研究中应分析 JAKi 的安全性概况，主要是关于恶性肿瘤和血栓栓塞事件的风险。
