Paton D M
University of Auckland, Auckland, New Zealand.
Drugs Today (Barc). 2016 Sep;52(9):485-493. doi: 10.1358/dot.2016.52.9.2542066.
Dry eye disease is an extremely common condition affecting millions worldwide. The underlying pathophysiological mechanism is thought to be localized inflammation of the ocular surface resulting in the localization of T cells at this surface followed by their activation and subsequent liberation of cytokines. This effect on T cells results from the binding of lymphocyte function-associated antigen-1 (LFA-1) located on T cells to intercellular adhesion molecule 1 (ICAM-1) expressed on inflamed epithelium and endothelium, and on T cells. Lifitegrast is a T-cell integrin antagonist designed to mimic ICAM-1, thus blocking the interaction of LFA-1 and ICAM-1. Lifitegrast enters the systemic circulation to a limited extent thus reducing the likelihood of unwanted systemic reactions. Clinical trials in over 2,500 subjects with dry eye disease have shown that 5.0% lifitegrast given by ocular instillation causes a significant reduction in objective and subjective signs and symptoms of the disease. These beneficial effects are associated with a relatively low incidence of unwanted effects, almost all local in nature. In light of these findings, lifitegrast was approved by the Food and Drug Administration (FDA) in 2016 for the treatment of dry eye disease, the first drug with this mechanism of action to be so approved.
干眼症是一种极为常见的病症，全球数以百万计的人受其影响。其潜在的病理生理机制被认为是眼表局部炎症，导致T细胞在该表面定位，随后被激活并释放细胞因子。对T细胞的这种作用是由T细胞上的淋巴细胞功能相关抗原-1（LFA-1）与炎症上皮和内皮以及T细胞上表达的细胞间黏附分子1（ICAM-1）结合所致。Lifitegrast是一种T细胞整合素拮抗剂，设计用于模拟ICAM-1，从而阻断LFA-1与ICAM-1的相互作用。Lifitegrast进入体循环的程度有限，因此降低了出现不良全身反应的可能性。对2500多名干眼症患者进行的临床试验表明，眼部滴注5.0%的Lifitegrast可显著减轻该疾病的客观和主观体征及症状。这些有益效果与不良作用的发生率相对较低相关，几乎所有不良作用本质上都是局部性的。鉴于这些研究结果，Lifitegrast于2016年被美国食品药品监督管理局（FDA）批准用于治疗干眼症，是首个获此作用机制批准的药物。
