Balevic Stephen J, Rabinovich C Egla
Department of Pediatric Rheumatology, Duke University Medical Center, Durham, NC, USA.
Drug Des Devel Ther. 2016 Sep 19;10:2997-3003. doi: 10.2147/DDDT.S94188. eCollection 2016.
Uveitis refers to the presence of intraocular inflammation, and as a strict definition compromises the iris and ciliary body anteriorly and the choroid posteriorly (the uvea). Untreated, uveitis can lead to visual loss or blindness. The etiology of uveitis can include both infectious and noninfectious (usually immune-mediated) causes, the latter of which are often mediated predominantly by Th1 CD4 T-cells that secrete proinflammatory cytokines. Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine involved in the pathogenesis of uveitis, which at high concentrations can cause excess inflammation and tissue damage. Adalimumab is a recombinant human IgG1 monoclonal antibody specific for human TNF-α. Historically, corticosteroids and methotrexate were used to treat uveitis; however, newer biologic agents such as adalimumab have revolutionized therapy for noninfectious uveitis. Adalimumab has shown efficacy in treating refractory uveitis in multiple settings, including idiopathic disease, juvenile idiopathic arthritis, sarcoidosis, Behçets disease, and uveitis secondary to spondyloarthropathies, among several other noninfectious uveitis conditions. In this paper, we will review the profile of adalimumab, the role of TNF-α in uveitis, discuss safety data, and summarize key articles evaluating the efficacy of adalimumab in treating uveitis secondary to the most commonly associated autoimmune diseases.
葡萄膜炎是指眼内存在炎症,严格定义包括前部的虹膜和睫状体以及后部的脉络膜(葡萄膜)。未经治疗,葡萄膜炎可导致视力丧失或失明。葡萄膜炎的病因可包括感染性和非感染性(通常是免疫介导的)原因,后者通常主要由分泌促炎细胞因子的Th1 CD4 T细胞介导。肿瘤坏死因子-α(TNF-α)是一种参与葡萄膜炎发病机制的促炎细胞因子,高浓度时可导致过度炎症和组织损伤。阿达木单抗是一种针对人TNF-α的重组人IgG1单克隆抗体。历史上,皮质类固醇和甲氨蝶呤曾用于治疗葡萄膜炎;然而,诸如阿达木单抗等新型生物制剂彻底改变了非感染性葡萄膜炎的治疗方法。阿达木单抗已在多种情况下显示出治疗难治性葡萄膜炎的疗效,包括特发性疾病、幼年特发性关节炎、结节病、白塞病以及继发于脊柱关节病的葡萄膜炎等其他几种非感染性葡萄膜炎情况。在本文中,我们将回顾阿达木单抗的概况、TNF-α在葡萄膜炎中的作用,讨论安全性数据,并总结评估阿达木单抗治疗继发于最常见相关自身免疫性疾病的葡萄膜炎疗效的关键文章。