Mechanisms behind efficacy of tumor necrosis factor inhibitors in inflammatory bowel diseases

TY - JOUR

T1 - Mechanisms behind efficacy of tumor necrosis factor inhibitors in inflammatory bowel diseases

AU - Olesen, Caroline Meyer

AU - Coskun, Mehmet

AU - Peyrin-Biroulet, Laurent

AU - Nielsen, Ole Haagen

N1 - Copyright © 2016 Elsevier Inc. All rights reserved.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Biological treatment with tumor necrosis factor (TNF) inhibitors is successful in the management of inflammatory bowel disease (IBD). All TNF inhibitors antagonize the pro-inflammatory cytokine TNF-α but with varying efficacies in IBD. The variations in efficacy probably are caused by structural differences between the agents that affect their mechanisms of action and pharmacokinetic properties. Several mechanisms have been proposed, such as modulation of the expression of pro-inflammatory mediators and a reduction in the number of activated immune cells. However, it seems that clinical efficacy is the result of a number of different mechanisms and that binding of transmembrane TNF by TNF inhibitors. Knowledge of the mechanisms of action has been obtained mainly through the use of in vitro assays that may differ significantly from the situation in vivo. This review discusses the available data on TNF inhibitors in order to identify mechanisms of importance for their efficacy in IBD. Thus, a better understanding of the mechanistic basis for clinical efficacy can lead to a more rational use of TNF inhibitors in the management of IBD.

AB - Biological treatment with tumor necrosis factor (TNF) inhibitors is successful in the management of inflammatory bowel disease (IBD). All TNF inhibitors antagonize the pro-inflammatory cytokine TNF-α but with varying efficacies in IBD. The variations in efficacy probably are caused by structural differences between the agents that affect their mechanisms of action and pharmacokinetic properties. Several mechanisms have been proposed, such as modulation of the expression of pro-inflammatory mediators and a reduction in the number of activated immune cells. However, it seems that clinical efficacy is the result of a number of different mechanisms and that binding of transmembrane TNF by TNF inhibitors. Knowledge of the mechanisms of action has been obtained mainly through the use of in vitro assays that may differ significantly from the situation in vivo. This review discusses the available data on TNF inhibitors in order to identify mechanisms of importance for their efficacy in IBD. Thus, a better understanding of the mechanistic basis for clinical efficacy can lead to a more rational use of TNF inhibitors in the management of IBD.

KW - Journal Article

KW - Review

U2 - 10.1016/j.pharmthera.2016.01.001

DO - 10.1016/j.pharmthera.2016.01.001

M3 - Journal article

C2 - 26808166

SN - 0163-7258

VL - 159

SP - 110

EP - 119

JO - Pharmacology & Therapeutics

JF - Pharmacology & Therapeutics

ER -