Systematic review genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases

Signe Bek Sørensen, J V Nielsen, Anders Bo Bojesen, A Franke, Steffen Bank, U Vogel, V Andersen

Publikation: Bidrag til tidsskriftReviewForskningpeer review

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Resumé

BACKGROUND: Personalised medicine, including biomarkers for treatment selection, may provide new algorithms for more effective treatment of patients. Genetic variation may impact drug response and genetic markers could help selecting the best treatment strategy for the individual patient.

AIM: To identify polymorphisms and candidate genes from the literature that are associated with anti-tumour necrosis factor (TNF) treatment response in patients with inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis.

METHODS: We performed a PubMed literature search and retrieved studies reporting original data on association between polymorphisms and anti-TNF treatment response and conducted a meta-analysis.

RESULTS: A functional polymorphism in FCGR3A was significantly associated with anti-TNF treatment response among CD patients using biological response criterion (decrease in C-reactive protein, levels). Meta-analyses showed that polymorphisms in TLR2 (rs3804099, OR (95% CI) = 2.17 (1.35-3.47)], rs11938228 [OR = 0.64 (0.43-0.96)], TLR4 (rs5030728) [OR = 3.18 (1.63-6.21)], TLR9 (rs352139) [OR = 0.43 (0.21-0.88)], TNFRSF1A (rs4149570) [OR = 2.06 (1.02-4.17)], IFNG (rs2430561) [OR = 1.66 (1.05-2.63)], IL6 (rs10499563) [OR = 1.65 (1.04-2.63)] and IL1B (rs4848306) [OR = 1.88 (1.05-3.35)] were significantly associated with response among IBD patients using clinical response criteria. A positive predictive value of 0.96 was achieved by combining five genetic markers in an explorative analysis.

CONCLUSIONS: There are no genetic markers currently available which are adequately predictive of anti-TNF response for use in the clinic. Genetic markers bear the advantage that they do not change over time. Therefore, hypothesis-free approaches, testing a large number of polymorphisms in large, well-characterised cohorts, are required in order to identify genetic profiles with larger effect sizes, which could be employed as biomarkers for treatment selection in clinical settings.

OriginalsprogEngelsk
TidsskriftAlimentary Pharmacology and Therapeutics
Vol/bind44
Udgave nummer6
Sider (fra-til)554-567
ISSN0269-2813
DOI
StatusUdgivet - 15. jul. 2016

Fingeraftryk

Inflammatory Bowel Diseases
Tumor Necrosis Factor-alpha
Genetic Markers
Crohn Disease
Meta-Analysis
Precision Medicine
Ulcerative Colitis
PubMed
Interleukin-6
Research Design
Pharmaceutical Preparations

Citer dette

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title = "Systematic review genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases",
abstract = "BACKGROUND: Personalised medicine, including biomarkers for treatment selection, may provide new algorithms for more effective treatment of patients. Genetic variation may impact drug response and genetic markers could help selecting the best treatment strategy for the individual patient.AIM: To identify polymorphisms and candidate genes from the literature that are associated with anti-tumour necrosis factor (TNF) treatment response in patients with inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis.METHODS: We performed a PubMed literature search and retrieved studies reporting original data on association between polymorphisms and anti-TNF treatment response and conducted a meta-analysis.RESULTS: A functional polymorphism in FCGR3A was significantly associated with anti-TNF treatment response among CD patients using biological response criterion (decrease in C-reactive protein, levels). Meta-analyses showed that polymorphisms in TLR2 (rs3804099, OR (95{\%} CI) = 2.17 (1.35-3.47)], rs11938228 [OR = 0.64 (0.43-0.96)], TLR4 (rs5030728) [OR = 3.18 (1.63-6.21)], TLR9 (rs352139) [OR = 0.43 (0.21-0.88)], TNFRSF1A (rs4149570) [OR = 2.06 (1.02-4.17)], IFNG (rs2430561) [OR = 1.66 (1.05-2.63)], IL6 (rs10499563) [OR = 1.65 (1.04-2.63)] and IL1B (rs4848306) [OR = 1.88 (1.05-3.35)] were significantly associated with response among IBD patients using clinical response criteria. A positive predictive value of 0.96 was achieved by combining five genetic markers in an explorative analysis.CONCLUSIONS: There are no genetic markers currently available which are adequately predictive of anti-TNF response for use in the clinic. Genetic markers bear the advantage that they do not change over time. Therefore, hypothesis-free approaches, testing a large number of polymorphisms in large, well-characterised cohorts, are required in order to identify genetic profiles with larger effect sizes, which could be employed as biomarkers for treatment selection in clinical settings.",
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Systematic review genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases. / Sørensen, Signe Bek; Nielsen, J V; Bo Bojesen, Anders; Franke, A; Bank, Steffen; Vogel, U; Andersen, V.

I: Alimentary Pharmacology and Therapeutics, Bind 44, Nr. 6, 15.07.2016, s. 554-567.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

TY - JOUR

T1 - Systematic review genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases

AU - Sørensen, Signe Bek

AU - Nielsen, J V

AU - Bo Bojesen, Anders

AU - Franke, A

AU - Bank, Steffen

AU - Vogel, U

AU - Andersen, V

N1 - © 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

PY - 2016/7/15

Y1 - 2016/7/15

N2 - BACKGROUND: Personalised medicine, including biomarkers for treatment selection, may provide new algorithms for more effective treatment of patients. Genetic variation may impact drug response and genetic markers could help selecting the best treatment strategy for the individual patient.AIM: To identify polymorphisms and candidate genes from the literature that are associated with anti-tumour necrosis factor (TNF) treatment response in patients with inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis.METHODS: We performed a PubMed literature search and retrieved studies reporting original data on association between polymorphisms and anti-TNF treatment response and conducted a meta-analysis.RESULTS: A functional polymorphism in FCGR3A was significantly associated with anti-TNF treatment response among CD patients using biological response criterion (decrease in C-reactive protein, levels). Meta-analyses showed that polymorphisms in TLR2 (rs3804099, OR (95% CI) = 2.17 (1.35-3.47)], rs11938228 [OR = 0.64 (0.43-0.96)], TLR4 (rs5030728) [OR = 3.18 (1.63-6.21)], TLR9 (rs352139) [OR = 0.43 (0.21-0.88)], TNFRSF1A (rs4149570) [OR = 2.06 (1.02-4.17)], IFNG (rs2430561) [OR = 1.66 (1.05-2.63)], IL6 (rs10499563) [OR = 1.65 (1.04-2.63)] and IL1B (rs4848306) [OR = 1.88 (1.05-3.35)] were significantly associated with response among IBD patients using clinical response criteria. A positive predictive value of 0.96 was achieved by combining five genetic markers in an explorative analysis.CONCLUSIONS: There are no genetic markers currently available which are adequately predictive of anti-TNF response for use in the clinic. Genetic markers bear the advantage that they do not change over time. Therefore, hypothesis-free approaches, testing a large number of polymorphisms in large, well-characterised cohorts, are required in order to identify genetic profiles with larger effect sizes, which could be employed as biomarkers for treatment selection in clinical settings.

AB - BACKGROUND: Personalised medicine, including biomarkers for treatment selection, may provide new algorithms for more effective treatment of patients. Genetic variation may impact drug response and genetic markers could help selecting the best treatment strategy for the individual patient.AIM: To identify polymorphisms and candidate genes from the literature that are associated with anti-tumour necrosis factor (TNF) treatment response in patients with inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis.METHODS: We performed a PubMed literature search and retrieved studies reporting original data on association between polymorphisms and anti-TNF treatment response and conducted a meta-analysis.RESULTS: A functional polymorphism in FCGR3A was significantly associated with anti-TNF treatment response among CD patients using biological response criterion (decrease in C-reactive protein, levels). Meta-analyses showed that polymorphisms in TLR2 (rs3804099, OR (95% CI) = 2.17 (1.35-3.47)], rs11938228 [OR = 0.64 (0.43-0.96)], TLR4 (rs5030728) [OR = 3.18 (1.63-6.21)], TLR9 (rs352139) [OR = 0.43 (0.21-0.88)], TNFRSF1A (rs4149570) [OR = 2.06 (1.02-4.17)], IFNG (rs2430561) [OR = 1.66 (1.05-2.63)], IL6 (rs10499563) [OR = 1.65 (1.04-2.63)] and IL1B (rs4848306) [OR = 1.88 (1.05-3.35)] were significantly associated with response among IBD patients using clinical response criteria. A positive predictive value of 0.96 was achieved by combining five genetic markers in an explorative analysis.CONCLUSIONS: There are no genetic markers currently available which are adequately predictive of anti-TNF response for use in the clinic. Genetic markers bear the advantage that they do not change over time. Therefore, hypothesis-free approaches, testing a large number of polymorphisms in large, well-characterised cohorts, are required in order to identify genetic profiles with larger effect sizes, which could be employed as biomarkers for treatment selection in clinical settings.

U2 - 10.1111/apt.13736

DO - 10.1111/apt.13736

M3 - Review

C2 - 27417569

VL - 44

SP - 554

EP - 567

JO - Alimentary Pharmacology and Therapeutics

JF - Alimentary Pharmacology and Therapeutics

SN - 0269-2813

IS - 6

ER -