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

8 Scopus citations

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

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

Fingerprint Dive into the research topics of 'Colonic Phenotypes Are Associated with Poorer Response to Anti-TNF Therapies in Patients with IBD'. Together they form a unique fingerprint.

  • Cite this

    Yoon, S. M., Haritunians, T., Chhina, S., Liu, Z., Yang, S., Landers, C., Li, D., Ye, B. D., Shih, D., Vasiliauskas, E. A., Ippoliti, A., Rabizadeh, S., Targan, S. R., Melmed, G. Y., & 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