Polygenetic risk scores do not add predictive power to clinical models for response to anti-TNFα therapy in inflammatory bowel disease.

<h4>Background</h4>Anti-tumour necrosis factor alpha (TNFα) therapy is widely used in the management of Crohn's disease (CD) and ulcerative colitis (UC). However, up to a third of patients do not respond to induction therapy and another third of patients lose response over time. To...

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Autores principales:	Naomi Karmi, Amber Bangma, Lieke M Spekhorst, Hendrik M van Dullemen, Marijn C Visschedijk, Gerard Dijkstra, Rinse K Weersma, Michiel D Voskuil, Eleonora A M Festen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7e6c3516725d43519dd43909c7f20bd4
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spelling	oai:doaj.org-article:7e6c3516725d43519dd43909c7f20bd42021-12-02T20:14:33ZPolygenetic risk scores do not add predictive power to clinical models for response to anti-TNFα therapy in inflammatory bowel disease.1932-620310.1371/journal.pone.0256860https://doaj.org/article/7e6c3516725d43519dd43909c7f20bd42021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256860https://doaj.org/toc/1932-6203<h4>Background</h4>Anti-tumour necrosis factor alpha (TNFα) therapy is widely used in the management of Crohn's disease (CD) and ulcerative colitis (UC). However, up to a third of patients do not respond to induction therapy and another third of patients lose response over time. To aid patient stratification, polygenetic risk scores have been identified as predictors of response to anti-TNFα therapy. We aimed to replicate the association between polygenetic risk scores and response to anti-TNFα therapy in an independent cohort of patients, to establish its clinical validity.<h4>Materials and methods</h4>Primary non-response, primary response, durable response and loss of response to anti-TNFα therapy was retrospectively assessed for each patient using stringent definitions. Genome wide genotyping was performed and previously described polygenetic risk scores for primary non-response and durable response were calculated. We compared polygenetic risk scores between patients with primary response and primary non-response, and between patients with durable response and loss of response, using separate analyses for CD and UC.<h4>Results</h4>Out of 334 patients with CD, 15 (4%) patients met criteria for primary non-response, 221 (66%) for primary response, 115 (34%) for durable response and 35 (10%) for loss of response. Out of 112 patients with UC, 12 (11%) met criteria for primary non-response, 68 (61%) for primary response, 19 (17%) for durable response and 20 (18%) for loss of response. No significant differences in polygenetic risk scores were found between primary non-responders and primary responders, and between durable responders and loss of responders.<h4>Conclusions</h4>We could not replicate the previously reported association between polygenetic risk scores and response to anti-TNFα therapy in an independent cohort of patients with CD or UC. Currently, there is insufficient evidence to use polygenetic risk scores to predict response to anti-TNFα therapy in patients with IBD.Naomi KarmiAmber BangmaLieke M SpekhorstHendrik M van DullemenMarijn C VisschedijkGerard DijkstraRinse K WeersmaMichiel D VoskuilEleonora A M FestenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0256860 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Naomi Karmi Amber Bangma Lieke M Spekhorst Hendrik M van Dullemen Marijn C Visschedijk Gerard Dijkstra Rinse K Weersma Michiel D Voskuil Eleonora A M Festen Polygenetic risk scores do not add predictive power to clinical models for response to anti-TNFα therapy in inflammatory bowel disease.
description	<h4>Background</h4>Anti-tumour necrosis factor alpha (TNFα) therapy is widely used in the management of Crohn's disease (CD) and ulcerative colitis (UC). However, up to a third of patients do not respond to induction therapy and another third of patients lose response over time. To aid patient stratification, polygenetic risk scores have been identified as predictors of response to anti-TNFα therapy. We aimed to replicate the association between polygenetic risk scores and response to anti-TNFα therapy in an independent cohort of patients, to establish its clinical validity.<h4>Materials and methods</h4>Primary non-response, primary response, durable response and loss of response to anti-TNFα therapy was retrospectively assessed for each patient using stringent definitions. Genome wide genotyping was performed and previously described polygenetic risk scores for primary non-response and durable response were calculated. We compared polygenetic risk scores between patients with primary response and primary non-response, and between patients with durable response and loss of response, using separate analyses for CD and UC.<h4>Results</h4>Out of 334 patients with CD, 15 (4%) patients met criteria for primary non-response, 221 (66%) for primary response, 115 (34%) for durable response and 35 (10%) for loss of response. Out of 112 patients with UC, 12 (11%) met criteria for primary non-response, 68 (61%) for primary response, 19 (17%) for durable response and 20 (18%) for loss of response. No significant differences in polygenetic risk scores were found between primary non-responders and primary responders, and between durable responders and loss of responders.<h4>Conclusions</h4>We could not replicate the previously reported association between polygenetic risk scores and response to anti-TNFα therapy in an independent cohort of patients with CD or UC. Currently, there is insufficient evidence to use polygenetic risk scores to predict response to anti-TNFα therapy in patients with IBD.
format	article
author	Naomi Karmi Amber Bangma Lieke M Spekhorst Hendrik M van Dullemen Marijn C Visschedijk Gerard Dijkstra Rinse K Weersma Michiel D Voskuil Eleonora A M Festen
author_facet	Naomi Karmi Amber Bangma Lieke M Spekhorst Hendrik M van Dullemen Marijn C Visschedijk Gerard Dijkstra Rinse K Weersma Michiel D Voskuil Eleonora A M Festen
author_sort	Naomi Karmi
title	Polygenetic risk scores do not add predictive power to clinical models for response to anti-TNFα therapy in inflammatory bowel disease.
title_short	Polygenetic risk scores do not add predictive power to clinical models for response to anti-TNFα therapy in inflammatory bowel disease.
title_full	Polygenetic risk scores do not add predictive power to clinical models for response to anti-TNFα therapy in inflammatory bowel disease.
title_fullStr	Polygenetic risk scores do not add predictive power to clinical models for response to anti-TNFα therapy in inflammatory bowel disease.
title_full_unstemmed	Polygenetic risk scores do not add predictive power to clinical models for response to anti-TNFα therapy in inflammatory bowel disease.
title_sort	polygenetic risk scores do not add predictive power to clinical models for response to anti-tnfα therapy in inflammatory bowel disease.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/7e6c3516725d43519dd43909c7f20bd4
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Polygenetic risk scores do not add predictive power to clinical models for response to anti-TNFα therapy in inflammatory bowel disease.

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