Anti-integrin therapy for inflammatory bowel disease

Abstract

In inflammatory bowel disease (IBD), tumor necrosis factor plays an important role in mediating inflammation, but several other pathways are also involved in eliciting an inflammatory response. One such pathway is the invasion of the intestinal mucosa by leukocytes. Leukocytes within the systemic circulation move to sites of inflammation, and blocking this pathway could be an important treatment strategy for IBD. Anti-integrin therapy blocks the action of integrin on the surface of circulating immune cells and endothelial cell adhesion molecules, thereby inhibiting the interactions between leukocytes and intestinal blood vessels. Natalizumab, which acts on alpha 4-integrin, was the first such drug to be approved for Crohn's disease, but its use is limited due to the risk of progressive multifocal leukoencephalopathy. Vedolizumab produces few systemic adverse effects because it acts on gut-trophic alpha 4 beta 7 integrin, and has been approved and is being used to treat IBD. Currently, several anti-integrin drugs, including etrolizumab, which acts on beta 7-integrin, and PF-00547569, which targets mucosal addressin cell adhesion molecule-1, are undergoing clinical trials and the results are being closely watched.