Abstract: Janus kinase (JAK) Inhibitors are the latest drug class of disease-modifying medication to emerge for the treatment of rheumatoid arthritis (RA). They are a small molecule-targeted treatment and are the first oral option to compare favourably to existing biologic disease-modifying anti-rheumatic drugs (DMARDs). Tofacitinib, baricitinib and upadacitinib are the first 3 JAK inhibitors to become commercially available in the field and are the core focus of this review. To date, they have demonstrated comparable efficacy to tumour necrosis factor (TNF) inhibitors in terms of American College of Rheumatology (ACR) response rates and disease activity (DAS28) scores with similar cost to the benchmark adalimumab. This narrative review article aims to synthesise and distil the key available trial data on JAK inhibitor efficacy and safety, along with their place in the ACR and European League Against Rheumatism (EULAR) guidelines for RA. The novel mechanism of action of the JAK/STAT pathway is highlighted along with the potential effects of modulating each pathway. The rapid onset of action, role in attenuation of central pain processing and effect on structural damage and radiographic progression are also all examined in detail. We also explore the latest meta-analyses and comparative performance of each of the 3 available JAKs in an effort to determine which is most efficacious and which has the most favourable safety profile. Post marketing concerns regarding thromboembolism risk and herpes zoster infection are also discussed. Additionally, we review the cost-benefit analyses of the available JAK inhibitors and address some of the pharmacoeconomic considerations for real-world practice in the UK and US by detailing the raw acquisition cost and the value they provide in comparison to the benchmark biologic adalimumab and the anchor DMARD methotrexate.

Keywords: rheumatoid arthritis, immunosuppressive therapies, JAK inhibitors, targeted synthetic DMARD, tsDMARD


中文翻译：

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JAK 抑制剂治疗类风湿关节炎：对新兴临床数据的循证审查


摘要： Janus 激酶 (JAK) 抑制剂是用于治疗类风湿性关节炎 (RA) 的最新一类疾病缓解药物。它们是一种小分子靶向治疗方法，是第一个可与现有生物疾病缓解抗风湿药物 (DMARD) 相媲美的口服选择。托法替尼、巴瑞替尼和乌帕替尼是首批在该领域商业化的 3 种 JAK 抑制剂，也是本次综述的核心焦点。迄今为止，它们在美国风湿病学会 (ACR) 缓解率和疾病活动 (DAS28) 评分方面已证明与肿瘤坏死因子 (TNF) 抑制剂相当，且成本与基准阿达木单抗相似。这篇叙述性综述文章旨在综合和提炼有关 JAK 抑制剂功效和安全性的关键可用试验数据，以及它们在 ACR 和欧洲抗风湿病联盟 (EULAR) RA 指南中的地位。重点介绍了 JAK/STAT 通路的新颖作用机制以及调节每个通路的潜在影响。还详细检查了快速起效、减轻中枢疼痛处理的作用以及对结构损伤和放射学进展的影响。我们还探索了 3 种可用 JAK 中每一种的最新荟萃分析和性能比较，以确定哪种最有效且哪种具有最有利的安全性。还讨论了有关血栓栓塞风险和带状疱疹感染的上市后问题。 此外，我们回顾了现有 JAK 抑制剂的成本效益分析，并通过详细说明原始采购成本及其与基准生物阿达木单抗和锚定 DMARD 甲氨蝶呤。


关键词：类风湿关节炎，免疫抑制治疗，JAK抑制剂，靶向合成DMARD，tsDMARD