Tanaka Yoshiya
University of Occupational and Environmental Health Japan, Kitakyushu, Japan.
Expert Opin Pharmacother. 2023 Sep-Dec;24(16):1791-1798. doi: 10.1080/14656566.2023.2247325. Epub 2023 Aug 14.
The molecular targeted therapies available for rheumatoid arthritis include 10 types of biological disease-modifying antirheumatic drugs (bDMARDs) and five types of Janus kinase (JAK) inhibitors. This article reviews the differential and proper use of bDMARDs and JAK inhibitors, focusing on their efficacy and safety, based mainly on phase III clinical trials.
The JAK inhibitors approved for treating rheumatoid arthritis are compared with bDMARDs based on the evidence derived from global phase III trials.
In patients with inadequate responses to bDMARDs and JAK inhibitors, switching between these drugs is comparable in efficacy in both directions. Head-to-head comparison demonstrated that baricitinib and upadacitinib are more efficacious than tumor necrosis factor (TNF) inhibitors. However, the ORAL Surveillance study demonstrated that JAK inhibitors are associated with higher incidences of death, major adverse cardiovascular events, malignancies and thrombosis than TNF inhibitors in at-risk patients. The need for risk assessment by pre-treatment screening, regular monitoring during treatment, and appropriate systemic management in adverse events should be recognized. Meanwhile, some JAK-inhibitors were efficacious even for difficult-to-treat disease. These results suggest the need for establishing therapeutic strategies considering the balance between safety and efficacy in individual patients.
可用于类风湿关节炎的分子靶向疗法包括10种生物改善病情抗风湿药（bDMARDs）和5种Janus激酶（JAK）抑制剂。本文主要基于III期临床试验，综述bDMARDs和JAK抑制剂的差异及合理使用，重点关注其疗效和安全性。
基于全球III期试验获得的证据，将已获批用于治疗类风湿关节炎的JAK抑制剂与bDMARDs进行比较。
对bDMARDs和JAK抑制剂反应不足的患者，在这两种药物之间转换的双向疗效相当。头对头比较表明，巴瑞替尼和乌帕替尼比肿瘤坏死因子（TNF）抑制剂更有效。然而，口服监测研究表明，在高危患者中，JAK抑制剂比TNF抑制剂与更高的死亡、主要不良心血管事件、恶性肿瘤和血栓形成发生率相关。应认识到通过治疗前筛查进行风险评估、治疗期间定期监测以及对不良事件进行适当系统管理的必要性。同时，一些JAK抑制剂即使对难治性疾病也有效。这些结果表明，需要制定考虑个体患者安全性和疗效平衡的治疗策略。
