Rheumatology Department, Royal Hallamshire Hospital, Sheffield, UK.
Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UK.
Expert Opin Pharmacother. 2022 Feb;23(2):169-173. doi: 10.1080/14656566.2021.2006183. Epub 2022 Jan 11.
Psoriatic arthritis is an extra-cutaneous manifestation affecting up to 40% of psoriasis patients with multiple therapies recommended by international guidelines including conventional and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) as well as biologics. Janus kinase inhibitors (JAKis) have emerged as a unique therapeutic target with tofacitinib the first to gain FDA approval in 2017. The non-selectivity of older JAKis increases the risk of off-target effects such as suppression of hemopoiesis hence the rationale for more selective alternatives.
This paper explores the use of upadacitinib (a selective JAK1 inhibitor) for the treatment of psoriatic arthritis. It covers its chemical properties, pharmacokinetics, pharmacodynamics, efficacy, safety and regulation.
In our opinion, upadacitinib is set to play an important role in the treatment of psoriatic arthritis as demonstrated by the SELECT-PsA trials especially in patients with poor or non-response to current first-line therapies. It's JAK1 receptor selectivity promises a lower side effect profile compared to the older nonselective JAKis but this will require confirmation with long-term clinical trial data.
银屑病关节炎是一种皮肤外表现，影响多达 40%的银屑病患者，国际指南推荐了多种治疗方法，包括传统和靶向合成的疾病修饰抗风湿药物（DMARDs）以及生物制剂。Janus 激酶抑制剂（JAKi）作为一种独特的治疗靶点已经出现，托法替尼于 2017 年首次获得 FDA 批准。较老的 JAKi 的非选择性增加了脱靶效应的风险，例如造血抑制，因此需要更具选择性的替代品。
本文探讨了巴瑞替尼（一种选择性 JAK1 抑制剂）在治疗银屑病关节炎中的应用。涵盖了其化学性质、药代动力学、药效学、疗效、安全性和监管情况。
在我们看来，正如 SELECT-PsA 试验所示，巴瑞替尼将在银屑病关节炎的治疗中发挥重要作用，尤其是在对当前一线治疗反应不佳或无反应的患者中。与较老的非选择性 JAKi 相比，它对 JAK1 受体的选择性有望降低副作用谱，但这需要长期临床试验数据的证实。
