Department of Dermatology and STD, Tufts Medical Center, 800 Washington Street, Box114, Boston, MA 02111, USA.
Ther Adv Musculoskelet Dis. 2013 Oct;5(5):277-85. doi: 10.1177/1759720X13501021.
Ustekinumab (UST) is a fully human immunoglobulin G1κ (IgG1κ) monoclonal antibody against common sub-unit p40 of interleukin-12 (IL-12) and interleukin-23 (IL-23). IL-12 and IL-23 are essential components of the Th1 and Th17 inflammatory pathways, respectively, and are the key mediators of psoriasis. Psoriatic arthritis (PsA), an important systemic inflammatory disorder, has similar pathogenesis to psoriasis. Many of PsA patients do not respond to tumor necrosis factor (TNF) inhibitor therapy, highlighting the need for additional treatment modalities with distinct mechanisms of action. Also, many patients stop responding to these agents after a certain period of use. A significant number of patients have a recurrent course or a persistent disease process. To meet these challenges a new agent working on different inflammatory aspect of PsA is needed. UST has been demonstrated to be effective, safe on short-term use and convenient in the treatment of plaque psoriasis and PsA. Long-term safety is still a concern. Until recently, the exact role of UST in the management of PsA had not been very clear. This article reviews the mechanism of action, pharmacokinetics, efficacy, safety profile and the clinical potential of UST in patients with PsA. We also discuss the three major trials conducted to show the efficacy and safety of UST in PsA.
乌司奴单抗(UST)是一种针对白细胞介素-12(IL-12)和白细胞介素-23(IL-23)共同亚单位 p40 的全人源免疫球蛋白 G1κ(IgG1κ)单克隆抗体。IL-12 和 IL-23 分别是 Th1 和 Th17 炎症途径的重要组成部分,是银屑病的关键介质。银屑病关节炎(PsA)是一种重要的系统性炎症性疾病,其发病机制与银屑病相似。许多 PsA 患者对肿瘤坏死因子(TNF)抑制剂治疗无反应,这凸显了需要具有不同作用机制的额外治疗方法。此外,许多患者在使用一定时间后停止对这些药物产生反应。相当数量的患者疾病反复发作或持续存在。为了应对这些挑战,需要一种针对 PsA 不同炎症方面的新型药物。UST 已被证明在治疗斑块状银屑病和 PsA 方面短期使用有效、安全且方便。长期安全性仍是一个关注点。直到最近,UST 在 PsA 管理中的确切作用还不是很清楚。本文综述了 UST 在 PsA 患者中的作用机制、药代动力学、疗效、安全性概况以及临床潜力。我们还讨论了三项旨在展示 UST 在 PsA 中的疗效和安全性的主要试验。