University of Maryland, Department of Medicine, Division of Gastroenterology & Hepatology, Baltimore, MD 21201, USA.
Immunotherapy. 2012 Sep;4(9):883-98. doi: 10.2217/imt.12.85.
Crohn's disease and ulcerative colitis are chronic, relapsing inflammatory disorders of the GI tract. In both Crohn's disease and ulcerative colitis, leukocytic infiltration of the mucosa is associated with epithelial damage. Recently, monoclonal antibodies directed against cell adhesion molecules (CAMs) involved in leukocyte extravasation have been developed. Natalizumab, the first drug brought to market targeting CAMs, is clinically effective but is associated with serious adverse effects including the uncommon, but often fatal, neurological disease progressive multifocal leukoencephalopathy. Vedolizumab targets a subset of the CAMs blocked by natalizumab and is currently in Phase III trials to study its efficacy and safety in patients with inflammatory bowel disease. Here, we discuss the current treatment options available for patients with Crohn's disease or ulcerative colitis, the history of CAM inhibitors, the current state of development of vedolizumab and its future role in inflammatory bowel disease, if approved by regulatory agencies.
克罗恩病和溃疡性结肠炎是胃肠道的慢性、复发性炎症性疾病。在克罗恩病和溃疡性结肠炎中，白细胞浸润黏膜与上皮损伤有关。最近，已经开发出针对参与白细胞渗出的细胞粘附分子（CAM）的单克隆抗体。那他珠单抗是靶向 CAM 的第一种上市药物，具有临床疗效，但与严重不良反应相关，包括不常见但通常致命的神经疾病——进行性多灶性白质脑病。Vedolizumab 靶向那他珠单抗阻断的 CAM 亚类，目前正在进行 III 期临床试验，以研究其在炎症性肠病患者中的疗效和安全性。在这里，我们讨论了目前可用于克罗恩病或溃疡性结肠炎患者的治疗选择、CAM 抑制剂的历史、vedolizumab 的当前开发状况及其在炎症性肠病中的未来作用，如果获得监管机构批准。
