Colonic Phenotypes Are Associated with Poorer Response to Anti-TNF Therapies in Patients with IBD

Soon Man Yoon, Talin Haritunians, Sultan Chhina, Zhenqiu Liu, Shaohong Yang, Carol Landers, Dalin Li, Byong Duk Ye, David Shih, Eric A. Vasiliauskas, Andrew Ippoliti, Shervin Rabizadeh, Stephan R. Targan, Gil Y. Melmed, Dermot P.B. McGovern

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Although anti-tumor necrosis factor (TNF) agents are effective in patients with inflammatory bowel disease (IBD), many patients either do not respond to anti-TNF treatment or lose response over time. The aim of this study was to determine factors associated with response to anti-TNF therapy in IBD. Methods: Patients with Crohn's disease (CD) or ulcerative colitis who had consented to participate in a genetics registry and been treated with anti-TNF agents were evaluated retrospectively and categorized as primary nonresponders or secondary nonresponders. We evaluated clinical, serological, and genetic characteristics associated with primary nonresponse or time to loss of response to anti-TNF agents. Results: We included 314 CD (51 [16.2%] primary nonresponders and 179 [57.0%] secondary nonresponders) and 145 subjects with ulcerative colitis (43 [29.7%] primary nonresponders and 74 [51.0%] secondary nonresponders). Colonic involvement (P = 0.017; odds ratio = 8.0) and anti-TNF monotherapy (P = 0.017; odds ratio = 4.9) were associated in a multivariate analysis with primary nonresponse to anti-TNF agents in CD. In addition, higher anti-nuclear cytoplasmic antibody levels (P = 0.019; hazard ratio = 1.01) in CD, anti-nuclear cytoplasmic antibody positivity (P = 0.038; hazard ratio = 1.6) in ulcerative colitis, and a positive family history of IBD (P = 0.044; hazard ratio = 1.3) in all patients with IBD were associated with time to loss of response to anti-TNF agents. Furthermore, various known IBD susceptibility single-nucleotide polymorphisms and additional variants in immune-mediated genes were shown to be associated with primary nonresponse or time to loss of response. Conclusions: Our results may help to optimize the use of anti-TNF agents in clinical practice and position these therapies appropriately as clinicians strive for a more personalized approach to managing IBD.

Original languageEnglish (US)
Pages (from-to)1382-1393
Number of pages12
JournalInflammatory bowel diseases
Volume23
Issue number8
DOIs
StatePublished - Aug 1 2017

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Inflammatory Bowel Diseases
Tumor Necrosis Factor-alpha
Phenotype
Crohn Disease
Ulcerative Colitis
Therapeutics
Odds Ratio
Antibodies
Disease Susceptibility
Single Nucleotide Polymorphism
Registries
Multivariate Analysis
Genes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

Cite this

Yoon, S. M., Haritunians, T., Chhina, S., Liu, Z., Yang, S., Landers, C., ... McGovern, D. P. B. (2017). Colonic Phenotypes Are Associated with Poorer Response to Anti-TNF Therapies in Patients with IBD. Inflammatory bowel diseases, 23(8), 1382-1393. https://doi.org/10.1097/MIB.0000000000001150
Yoon, Soon Man ; Haritunians, Talin ; Chhina, Sultan ; Liu, Zhenqiu ; Yang, Shaohong ; Landers, Carol ; Li, Dalin ; Ye, Byong Duk ; Shih, David ; Vasiliauskas, Eric A. ; Ippoliti, Andrew ; Rabizadeh, Shervin ; Targan, Stephan R. ; Melmed, Gil Y. ; McGovern, Dermot P.B. / Colonic Phenotypes Are Associated with Poorer Response to Anti-TNF Therapies in Patients with IBD. In: Inflammatory bowel diseases. 2017 ; Vol. 23, No. 8. pp. 1382-1393.
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abstract = "Background: Although anti-tumor necrosis factor (TNF) agents are effective in patients with inflammatory bowel disease (IBD), many patients either do not respond to anti-TNF treatment or lose response over time. The aim of this study was to determine factors associated with response to anti-TNF therapy in IBD. Methods: Patients with Crohn's disease (CD) or ulcerative colitis who had consented to participate in a genetics registry and been treated with anti-TNF agents were evaluated retrospectively and categorized as primary nonresponders or secondary nonresponders. We evaluated clinical, serological, and genetic characteristics associated with primary nonresponse or time to loss of response to anti-TNF agents. Results: We included 314 CD (51 [16.2{\%}] primary nonresponders and 179 [57.0{\%}] secondary nonresponders) and 145 subjects with ulcerative colitis (43 [29.7{\%}] primary nonresponders and 74 [51.0{\%}] secondary nonresponders). Colonic involvement (P = 0.017; odds ratio = 8.0) and anti-TNF monotherapy (P = 0.017; odds ratio = 4.9) were associated in a multivariate analysis with primary nonresponse to anti-TNF agents in CD. In addition, higher anti-nuclear cytoplasmic antibody levels (P = 0.019; hazard ratio = 1.01) in CD, anti-nuclear cytoplasmic antibody positivity (P = 0.038; hazard ratio = 1.6) in ulcerative colitis, and a positive family history of IBD (P = 0.044; hazard ratio = 1.3) in all patients with IBD were associated with time to loss of response to anti-TNF agents. Furthermore, various known IBD susceptibility single-nucleotide polymorphisms and additional variants in immune-mediated genes were shown to be associated with primary nonresponse or time to loss of response. Conclusions: Our results may help to optimize the use of anti-TNF agents in clinical practice and position these therapies appropriately as clinicians strive for a more personalized approach to managing IBD.",
author = "Yoon, {Soon Man} and Talin Haritunians and Sultan Chhina and Zhenqiu Liu and Shaohong Yang and Carol Landers and Dalin Li and Ye, {Byong Duk} and David Shih and Vasiliauskas, {Eric A.} and Andrew Ippoliti and Shervin Rabizadeh and Targan, {Stephan R.} and Melmed, {Gil Y.} and McGovern, {Dermot P.B.}",
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Yoon, SM, Haritunians, T, Chhina, S, Liu, Z, Yang, S, Landers, C, Li, D, Ye, BD, Shih, D, Vasiliauskas, EA, Ippoliti, A, Rabizadeh, S, Targan, SR, Melmed, GY & McGovern, DPB 2017, 'Colonic Phenotypes Are Associated with Poorer Response to Anti-TNF Therapies in Patients with IBD', Inflammatory bowel diseases, vol. 23, no. 8, pp. 1382-1393. https://doi.org/10.1097/MIB.0000000000001150

Colonic Phenotypes Are Associated with Poorer Response to Anti-TNF Therapies in Patients with IBD. / Yoon, Soon Man; Haritunians, Talin; Chhina, Sultan; Liu, Zhenqiu; Yang, Shaohong; Landers, Carol; Li, Dalin; Ye, Byong Duk; Shih, David; Vasiliauskas, Eric A.; Ippoliti, Andrew; Rabizadeh, Shervin; Targan, Stephan R.; Melmed, Gil Y.; McGovern, Dermot P.B.

In: Inflammatory bowel diseases, Vol. 23, No. 8, 01.08.2017, p. 1382-1393.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Colonic Phenotypes Are Associated with Poorer Response to Anti-TNF Therapies in Patients with IBD

AU - Yoon, Soon Man

AU - Haritunians, Talin

AU - Chhina, Sultan

AU - Liu, Zhenqiu

AU - Yang, Shaohong

AU - Landers, Carol

AU - Li, Dalin

AU - Ye, Byong Duk

AU - Shih, David

AU - Vasiliauskas, Eric A.

AU - Ippoliti, Andrew

AU - Rabizadeh, Shervin

AU - Targan, Stephan R.

AU - Melmed, Gil Y.

AU - McGovern, Dermot P.B.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Background: Although anti-tumor necrosis factor (TNF) agents are effective in patients with inflammatory bowel disease (IBD), many patients either do not respond to anti-TNF treatment or lose response over time. The aim of this study was to determine factors associated with response to anti-TNF therapy in IBD. Methods: Patients with Crohn's disease (CD) or ulcerative colitis who had consented to participate in a genetics registry and been treated with anti-TNF agents were evaluated retrospectively and categorized as primary nonresponders or secondary nonresponders. We evaluated clinical, serological, and genetic characteristics associated with primary nonresponse or time to loss of response to anti-TNF agents. Results: We included 314 CD (51 [16.2%] primary nonresponders and 179 [57.0%] secondary nonresponders) and 145 subjects with ulcerative colitis (43 [29.7%] primary nonresponders and 74 [51.0%] secondary nonresponders). Colonic involvement (P = 0.017; odds ratio = 8.0) and anti-TNF monotherapy (P = 0.017; odds ratio = 4.9) were associated in a multivariate analysis with primary nonresponse to anti-TNF agents in CD. In addition, higher anti-nuclear cytoplasmic antibody levels (P = 0.019; hazard ratio = 1.01) in CD, anti-nuclear cytoplasmic antibody positivity (P = 0.038; hazard ratio = 1.6) in ulcerative colitis, and a positive family history of IBD (P = 0.044; hazard ratio = 1.3) in all patients with IBD were associated with time to loss of response to anti-TNF agents. Furthermore, various known IBD susceptibility single-nucleotide polymorphisms and additional variants in immune-mediated genes were shown to be associated with primary nonresponse or time to loss of response. Conclusions: Our results may help to optimize the use of anti-TNF agents in clinical practice and position these therapies appropriately as clinicians strive for a more personalized approach to managing IBD.

AB - Background: Although anti-tumor necrosis factor (TNF) agents are effective in patients with inflammatory bowel disease (IBD), many patients either do not respond to anti-TNF treatment or lose response over time. The aim of this study was to determine factors associated with response to anti-TNF therapy in IBD. Methods: Patients with Crohn's disease (CD) or ulcerative colitis who had consented to participate in a genetics registry and been treated with anti-TNF agents were evaluated retrospectively and categorized as primary nonresponders or secondary nonresponders. We evaluated clinical, serological, and genetic characteristics associated with primary nonresponse or time to loss of response to anti-TNF agents. Results: We included 314 CD (51 [16.2%] primary nonresponders and 179 [57.0%] secondary nonresponders) and 145 subjects with ulcerative colitis (43 [29.7%] primary nonresponders and 74 [51.0%] secondary nonresponders). Colonic involvement (P = 0.017; odds ratio = 8.0) and anti-TNF monotherapy (P = 0.017; odds ratio = 4.9) were associated in a multivariate analysis with primary nonresponse to anti-TNF agents in CD. In addition, higher anti-nuclear cytoplasmic antibody levels (P = 0.019; hazard ratio = 1.01) in CD, anti-nuclear cytoplasmic antibody positivity (P = 0.038; hazard ratio = 1.6) in ulcerative colitis, and a positive family history of IBD (P = 0.044; hazard ratio = 1.3) in all patients with IBD were associated with time to loss of response to anti-TNF agents. Furthermore, various known IBD susceptibility single-nucleotide polymorphisms and additional variants in immune-mediated genes were shown to be associated with primary nonresponse or time to loss of response. Conclusions: Our results may help to optimize the use of anti-TNF agents in clinical practice and position these therapies appropriately as clinicians strive for a more personalized approach to managing IBD.

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