IBD Center, Department of Gastroenterology, Istituto Clinico Humanitas, Milan, Italy.
Curr Drug Targets. 2013 Nov;14(12):1433-43. doi: 10.2174/13894501113146660206.
Inflammatory bowel diseases (IBD) are characterized by a persistent recruitment of large quantities of leucocytes from the blood to the gut mucosa. Adhesion molecules, such as integrins and their ligands, are the main players in this complex process. Leucocyte traffic control using a specific integrin inhibitors, such as natalizumab, has been plagued by severe systemic effects. The α4β7 - integrin and its ligand, the MadCAM-1, have been of special interest, since they are found exclusively on the gut-homing lymphocyte subpopulations and in the intestinal mucosa respectively. It follows that inhibition of such molecules should offer gut-specific immunosuppression, without the systemic effects of aspecific integrin- antagonists. We review the role of vedolizumab, a humanized antibody against the α4β7 - integrin, in both ulcerative colitis (UC) and Crohn's disease (CD). Results from clinical trials show that vedolizumab is effective in the induction and maintenance of remission in active CD and UC and has a very good safety profile. These data allow to confidently prospect that vedolizumab will be an important therapeutic option in the future of IBD treatment.
炎症性肠病（IBD）的特征是大量白细胞从血液持续募集到肠道黏膜。黏附分子，如整合素及其配体，是这一复杂过程的主要参与者。使用特定的整合素抑制剂（如那他珠单抗）控制白细胞迁移一直受到严重的全身作用的困扰。α4β7-整合素及其配体 MadCAM-1 特别受到关注，因为它们分别只存在于肠道归巢淋巴细胞亚群和肠道黏膜上。因此，抑制这些分子应该提供肠道特异性免疫抑制，而没有非特异性整合素拮抗剂的全身作用。我们回顾了 vedolizumab（一种针对 α4β7-整合素的人源化抗体）在溃疡性结肠炎（UC）和克罗恩病（CD）中的作用。临床试验的结果表明，vedolizumab 在活动期 CD 和 UC 的诱导和维持缓解方面有效，且具有良好的安全性特征。这些数据使我们有信心预测，vedolizumab 将成为未来 IBD 治疗的重要治疗选择。
