Cardiff University School of Medicine, Cardiff, Wales, UK.
Hôpitaux Universitaires Paris-Centre, Paris, France.
Clin Exp Rheumatol. 2019 Jul-Aug;37(4):694-704. Epub 2019 Feb 11.
Numerous cytokines have been implicated in the pathogenesis of inflammatory diseases, and their dysregulation is a main feature of rheumatoid arthritis (RA). Cytokines stimulate signal transduction through several intracellular pathways, including Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathways, leading to changes in cell activation, proliferation and survival. Consequently, agents that selectively target elements of the JAK/STAT pathways have received significant attention in recent years as potential new treatments for the disease. Baricitinib, an oral selective inhibitor of JAK1 and JAK2, offers an effective treatment for RA in a wide range of patients. The in vitro selectivity of different JAK inhibitors is an important consideration given that key cytokines, growth factors and hormone receptors involved in the pathogenesis of RA signal through specific JAKs. However, it is complex and far from understood how the in vitro effects of JAK inhibitors extrapolate into in vivo and clinical effects in individual patients. This narrative review focuses on the clinical efficacy and safety of baricitinib, but also provides an overview of its mechanism of action in relation to JAK1/JAK2 signalling and discusses the possible clinical implications in patients with RA.
许多细胞因子参与了炎症性疾病的发病机制，其失调是类风湿关节炎（RA）的主要特征。细胞因子通过几种细胞内途径刺激信号转导，包括 Janus 激酶（JAK）/信号转导和转录激活因子（STAT）途径，导致细胞激活、增殖和存活的变化。因此，近年来，选择性靶向 JAK/STAT 途径的药物作为该疾病的潜在新治疗方法受到了广泛关注。巴瑞替尼是一种口服选择性 JAK1 和 JAK2 抑制剂，为广泛的患者提供了有效的 RA 治疗。鉴于参与 RA 发病机制的关键细胞因子、生长因子和激素受体通过特定的 JAK 信号转导，不同 JAK 抑制剂的体外选择性是一个重要的考虑因素。然而，JAK 抑制剂的体外作用如何推断到个体患者的体内和临床效果，这是复杂的，远未被理解。本叙述性综述重点介绍了巴瑞替尼的临床疗效和安全性，但也概述了其与 JAK1/JAK2 信号转导相关的作用机制，并讨论了其在 RA 患者中的可能临床意义。
