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World J Gastroenterol. May 7, 2018; 24(17): 1868-1880
Published online May 7, 2018. doi: 10.3748/wjg.v24.i17.1868
Anti-integrin therapy for inflammatory bowel disease
Sung Chul Park, Yoon Tae Jeen
Sung Chul Park, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon 24289, South Korea
Yoon Tae Jeen, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul 02841, South Korea
Author contributions: Park SC and Jeen YT wrote the manuscript and made the tables and figures.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yoon Tae Jeen, MD, PhD, Professor, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, Seongbuk-gu, Seoul 02841, South Korea. ytjeen@korea.ac.kr
Telephone: +82-2-9206555 Fax: +82-2-9531943
Received: March 23, 2018
Peer-review started: March 25, 2018
First decision: April 18, 2018
Revised: April 23, 2018
Accepted: April 26, 2018
Article in press: April 26, 2018
Published online: May 7, 2018
Processing time: 44 Days and 6.3 Hours
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 α4-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 α4β7 integrin, and has been approved and is being used to treat IBD. Currently, several anti-integrin drugs, including etrolizumab, which acts on β7-integrin, and PF-00547569, which targets mucosal addressin cell adhesion molecule-1, are undergoing clinical trials and the results are being closely watched.

Keywords: Integrin; Ulcerative colitis; Crohn’s disease; Natalizumab; Abrilumab; Etrolizumab; PF-00547659; Inflammatory bowel disease; AJM300; Vedolizumab

Core tip: Anti-integrin therapies have attracted attention as new therapeutic agents in inflammatory bowel disease. They inhibit the extravasation of leukocytes by blocking the interaction between integrins on immune cells and endothelial cell adhesion molecules. The use of the first developed anti-integrin agent, natalizumab is now limited due to the risk of progressive multifocal leukoencephalopathy. However, vedolizumab which acts selectively on the gut has shown few adverse events and is currently used in clinical practice. Newer anti-integrin drugs that act on different integrins-related targets, such as AJM300, abrilumab, etrolizumab, and PF-00547659 have also been developed and are in clinical trials.