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IL-23 Blockade in Anti-TNF Refractory IBD: From Mechanisms to Clinical Reality

Increasing insights into the immunopathogenesis of inflammatory bowel diseases [IBD] have led to the advent of targeted therapies that inhibit crucial mediators of the inflammatory process, thereby widening our available therapeutic armamentarium. Anti-tumour necrosis factor [anti-TNF] agents are st...

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Autores principales: Atreya, Raja, Neurath, Markus F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097672/
https://www.ncbi.nlm.nih.gov/pubmed/35553662
http://dx.doi.org/10.1093/ecco-jcc/jjac007
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author Atreya, Raja
Neurath, Markus F
author_facet Atreya, Raja
Neurath, Markus F
author_sort Atreya, Raja
collection PubMed
description Increasing insights into the immunopathogenesis of inflammatory bowel diseases [IBD] have led to the advent of targeted therapies that inhibit crucial mediators of the inflammatory process, thereby widening our available therapeutic armamentarium. Anti-tumour necrosis factor [anti-TNF] agents are still a mainstay of our therapeutic endeavours and the introduction of corresponding biosimilars has further widened their use. Nevertheless, only a subgroup of treated patients benefit from the initiated treatment and there is secondary non-response in the course of therapy. Initiation of subsequent therapy often poses a challenge to the treating physician, as non-response to primary anti-TNF treatment generally characterizes a patient group that is more treatment-resistant, which may be due to the immunological impregnation by prior anti-TNF exposure. At present, there is currently no guidance for the most appropriate second-line therapy after anti-TNF failure. Here, we review the efficacy of secondary biological therapy in anti-TNF-treated patients. We focus on and assess available clinical trial data of the emerging substance class of IL-23p19 inhibitors, which have demonstrated remarkable efficacy not only in anti-TNF-naïve but also refractory patients. We present molecular mechanisms that drive IL-23-mediated resistance to ongoing anti-TNF therapy and discuss the dynamic fluidity of the mucosal cytokine network in the course of therapy that perpetuates the mucosal inflammatory reaction. Translation of these findings into clinical practice might finally lead to initiation of the most appropriate therapy at the right time of the individual disease course, which would have important implications for the patient’s probability of response to treatment.
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spelling pubmed-90976722022-05-13 IL-23 Blockade in Anti-TNF Refractory IBD: From Mechanisms to Clinical Reality Atreya, Raja Neurath, Markus F J Crohns Colitis Supplement Articles Increasing insights into the immunopathogenesis of inflammatory bowel diseases [IBD] have led to the advent of targeted therapies that inhibit crucial mediators of the inflammatory process, thereby widening our available therapeutic armamentarium. Anti-tumour necrosis factor [anti-TNF] agents are still a mainstay of our therapeutic endeavours and the introduction of corresponding biosimilars has further widened their use. Nevertheless, only a subgroup of treated patients benefit from the initiated treatment and there is secondary non-response in the course of therapy. Initiation of subsequent therapy often poses a challenge to the treating physician, as non-response to primary anti-TNF treatment generally characterizes a patient group that is more treatment-resistant, which may be due to the immunological impregnation by prior anti-TNF exposure. At present, there is currently no guidance for the most appropriate second-line therapy after anti-TNF failure. Here, we review the efficacy of secondary biological therapy in anti-TNF-treated patients. We focus on and assess available clinical trial data of the emerging substance class of IL-23p19 inhibitors, which have demonstrated remarkable efficacy not only in anti-TNF-naïve but also refractory patients. We present molecular mechanisms that drive IL-23-mediated resistance to ongoing anti-TNF therapy and discuss the dynamic fluidity of the mucosal cytokine network in the course of therapy that perpetuates the mucosal inflammatory reaction. Translation of these findings into clinical practice might finally lead to initiation of the most appropriate therapy at the right time of the individual disease course, which would have important implications for the patient’s probability of response to treatment. Oxford University Press 2022-05-11 /pmc/articles/PMC9097672/ /pubmed/35553662 http://dx.doi.org/10.1093/ecco-jcc/jjac007 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Supplement Articles
Atreya, Raja
Neurath, Markus F
IL-23 Blockade in Anti-TNF Refractory IBD: From Mechanisms to Clinical Reality
title IL-23 Blockade in Anti-TNF Refractory IBD: From Mechanisms to Clinical Reality
title_full IL-23 Blockade in Anti-TNF Refractory IBD: From Mechanisms to Clinical Reality
title_fullStr IL-23 Blockade in Anti-TNF Refractory IBD: From Mechanisms to Clinical Reality
title_full_unstemmed IL-23 Blockade in Anti-TNF Refractory IBD: From Mechanisms to Clinical Reality
title_short IL-23 Blockade in Anti-TNF Refractory IBD: From Mechanisms to Clinical Reality
title_sort il-23 blockade in anti-tnf refractory ibd: from mechanisms to clinical reality
topic Supplement Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097672/
https://www.ncbi.nlm.nih.gov/pubmed/35553662
http://dx.doi.org/10.1093/ecco-jcc/jjac007
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