Kyeong Ok Kim; Byung Ik Jang

doi:10.4166/kjg.2011.58.5.235

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Kim and Jang: Emerging Drugs in the Treatment of Inflammatory Bowel Disease: Beyond Anti-TNF-α

Review Article

Korean J Gastroenterol 2011;58(5):235-244.

Published online: 4 October 2011

DOI: https://doi.org/10.4166/kjg.2011.58.5.235

Emerging Drugs in the Treatment of Inflammatory Bowel Disease: Beyond Anti-TNF-α

Kyeong Ok Kim, Byung Ik Jang

Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea

Correspondence to: Byung Ik Jang, Division of Gastroenterology, Department of Internal Medicine, Yeungnam University College of Medicine, 317-1, Daemyung 5- dong, Nam-gu, Daegu 705-717, Korea. Tel: +82-53-620-3831, Fax: +82-53-654-8386, E-mail: jbi@med.yu.ac.kr

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Understanding of the pathophysiology of inflammatory bowel disease (IBD) is constantly evolving and, recently, a number of biologic agents have been developed. They selectively target specific molecule or pathways and correct the imbalance of the gut immune system. Among them, antibody to tumor necrosis factor (anti-TNF-α) is the first developed drugs, and it dramatically improved the IBD management. However, more than one-third of the patients do not respond to the drugs due to antibody formation. To increase treatment efficacy, enormous effort to develop novel anti-cytokines which can be an alternative to anti-TNF-α has been made. They are anti CD4＋ T cell cytokine including interleukin (IL)-12/23 and IL-17 blockers, selective anti-adhesion molecule known as natalizumab, vedolizumab and alicaforsen, T-cell proliferation inhibitor, anti-inflammatory cytokine, immune stimulator, growth factor, and mitogen-activated protein kinase inhibitor. The efficacy and safety of each drugs are under investigation. Some drugs reported very promising data, however, others showed disappointing and different results. In addition, most of the trials were done in a very small number of patients, and there is no trial comparing to anti-TNF-α. The present paper reviews the action mechanism, short or long term efficacy and safety of variable drugs other than anti-TNF-α in IBD.

Keywords: Inflammatory bowel disease, Therapeutics, Infliximab, Biological products

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Table 1.

Emerging Biologics in the Treatment of Inflammatory Bowel Diseases

Class of the drug	Target	Agent	Disease
Inhibitors of proinflammatory cytokines	Tumor necrosis factor	Infliximab	CD, UC
		Adalimumab	CD, UC
		Certolizumab pegol	CD
CD4+ T cell cytokine inhibitor	IL-12/23	ABT-874	CD
		Ustekinumab	CD
	IL-17	AIN457	CD
Adhesion molecule inhibitor	α4-integrin	Natalizumab	CD, UC
	α4β7-integrin	Vedolizumab	CD, UC
	MAdCAM-1	Alicaforsen	UC
Inhibitors of T cell proliferation	IL-2R	Basiliximab	UC
		Daclizumab	UC
	CD3	Visilizumab	UC
Anti-inflammatory cytokine	IL-10	Tenovil	CD, UC
	IL-11	Oprevil	CD
	Interferon (IFN)-α, β	IFN-α, β	CD, UC
Immunostimulator	G-CSF	Filgrastim	CD
	GM-CSF	Sargramostim	CD
Growth factors	Growth hormone	Somatropin	CD
	KGF	Repifermin	UC
	EGF	rHuEGF	UC
MAPK inhibitor	p28 MAPK/JNK	RDP-58	CD, UC
	p38 MAPK	BIRB-796	CD
	p38 MAPK/JNK	CNI-1493	CD

IL, interleukin; CD, Crohn's disese; UC, ulcerative colitis; MAdCAM, mucosal addressin cell adhesion molecule-1; CD, cluster of differentiation; G-CSF, granulocyte-colony stimulating factors; GM-CSF, granulocyte-monocyte stimulating factors; KGF, keratinocyte growth factor; EGF, epidermal growth factor; MAPK, mitogen-activated protein kinase; JNK, Jun-N-terminal kinase.

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