Cell Culture Laboratory, Biotechnology Graduate Program, Universidade do Vale do Taquari, Univates, Av. Avelino Talini, 171, Lajeado, RS, 95914-014, Brazil.
School of Dentistry, University Center Univates, Lajeado, RS, Brazil.
Inflammopharmacology. 2021 Jun;29(3):595-615. doi: 10.1007/s10787-021-00822-x. Epub 2021 May 27.
One-third of patients with severe rheumatoid arthritis (RA) do not achieve remission or low disease activity, or they have side effects from cDMARD and bDMARD. They will need a new treatment option such as the small molecule JAK inhibitors. In this systematic review, we evaluate the efficacy and safety data of the current jakinibs: tofacitinib, peficitinib, decernotinib, upadacitinib, baricitinib and filgotinib in patients in whom treatment with conventional or biological disease-modifying antirheumatic drugs (cDMARD and/or bDMARD) failed.
We searched for randomized controlled trials comparing efficacy and safety of jakinibs for RA treatment using the Web of Science, Scopus, PubMed, and clinicaltrials.gov databases with the terms: "rheumatoid arthritis" OR "arthritis rheumatoid" OR "RA" AND "inhibitor" OR "jak inhibitor" AND "clinical trial" OR "treatment" OR "therapy".
All jakinibs achieved good results in ACR 20, 50, 70 and with CRP-DAS28 for LDA and remission, upadacitinib showed better results compared to the others. In ESR-DAS28 for remission, tofacitinib achieved the best result. Regarding the safety of all jakinibs, peficitinib, baricitinib and filgotinib did not register deaths in their studies unlike tofacitinib that presented 11 deaths. Despite all benefits of jakinibs, the use in patients with severe liver and kidney disease should be avoided.
Jakinibs in monotherapy or in combination with methotrexate can be considered a viable alternative in the treatment of moderate-to-severe RA. Even after failures with combination of cDMARDS and bDMARDS, jakinibs demonstrated efficacy.
三分之一患有严重类风湿关节炎（RA）的患者未达到缓解或低疾病活动度，或因使用传统合成改善病情抗风湿药（csDMARD）和生物 DMARD 出现副作用。他们需要新的治疗选择，如小分子 JAK 抑制剂。在本系统评价中，我们评估了目前 JAK 抑制剂（托法替布、培非替尼、德塞替尼、乌帕替尼、巴瑞替尼和菲戈替尼）在接受常规或生物 DMARD 治疗失败的患者中的疗效和安全性数据。
我们使用 Web of Science、Scopus、PubMed 和 clinicaltrials.gov 数据库，使用“rheumatoid arthritis”或“arthritis rheumatoid”或“RA”和“inhibitor”或“jak inhibitor”和“clinical trial”或“treatment”或“therapy”等术语搜索比较 JAK 抑制剂治疗 RA 疗效和安全性的随机对照试验。
所有 JAK 抑制剂在 ACR 20、50、70 和 CRP-DAS28 方面达到低疾病活动度和缓解方面均取得了良好的结果，乌帕替尼与其他药物相比结果更好。在 ESR-DAS28 缓解方面，托法替布取得了最佳结果。关于所有 JAK 抑制剂的安全性，培非替尼、巴瑞替尼和菲戈替尼在其研究中未报告死亡，而托法替布报告了 11 例死亡。尽管 JAK 抑制剂有诸多益处，但应避免在严重肝肾功能不全患者中使用。
JAK 抑制剂单药或与甲氨蝶呤联合可作为中重度 RA 治疗的一种可行选择。即使在 csDMARD 和 bDMARD 联合治疗失败后，JAK 抑制剂仍显示出疗效。
