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Bank, Steffen; Julsgaard, Mette; Abed, Osama Karim; Burisch, Johan; Broder Brodersen, Jacob; Pedersen, Natalia Konstantinovich; Gouliaev, Anja; Ajan, Rullah; Nytoft Rasmussen, Ditlev; Honore Grauslund, Camilla; Roug, Stine; Galsgaard, Julie; Sprogøe Høyer Finsen, David; Lindby, Karoline; Sørensen, Jeanette; Larsen, Lone; Rohr Andersen, Malene; Brandslund, Ivan; Thomassen, Mads; Green, Anders; Bo Bojesen, Anders; Bek Sørensen, Signe; Vogel, Ulla; Andersen, Vibeke

Polymorphisms in the NFkB, TNF‐alpha, IL‐1beta, and IL‐18 pathways are associated with response to anti‐TNF therapy in Danish patients with inflammatory bowel disease

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  • Media type: E-Article
  • Title: Polymorphisms in the NFkB, TNF‐alpha, IL‐1beta, and IL‐18 pathways are associated with response to anti‐TNF therapy in Danish patients with inflammatory bowel disease
  • Contributor: Bank, Steffen; Julsgaard, Mette; Abed, Osama Karim; Burisch, Johan; Broder Brodersen, Jacob; Pedersen, Natalia Konstantinovich; Gouliaev, Anja; Ajan, Rullah; Nytoft Rasmussen, Ditlev; Honore Grauslund, Camilla; Roug, Stine; Galsgaard, Julie; Sprogøe Høyer Finsen, David; Lindby, Karoline; Sørensen, Jeanette; Larsen, Lone; Rohr Andersen, Malene; Brandslund, Ivan; Thomassen, Mads; Green, Anders; Bo Bojesen, Anders; Bek Sørensen, Signe; Vogel, Ulla; Andersen, Vibeke
  • Published: Wiley, 2019
  • Published in: Alimentary Pharmacology & Therapeutics, 49 (2019) 7, Seite 890-903
  • Language: English
  • DOI: 10.1111/apt.15187
  • ISSN: 0269-2813; 1365-2036
  • Origination:
  • Footnote:
  • Description: SummaryBackgroundAnti‐tumor necrosis factor‐α (TNF‐α) is used for the treatment of severe cases of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). However, one‐third of the patients do not respond to the treatment. We have previously investigated whether single nucleotide polymorphisms (SNPs) in genes involved in inflammation were associated with response to anti‐TNF therapy among patients with CD or UC.AimA new cohort of patients was established for replication of the previous findings and to identify new SNPs associated with anti‐TNF response.MethodsFifty‐three SNPs assessed previously in cohort 1 (482 CD and 256 UC patients) were genotyped in cohort 2 (587 CD and 458 UC patients). The results were analysed using logistic regression (adjusted for age and gender).ResultsTen SNPs were associated with anti‐TNF response either among patients with CD (TNFRSF1A(rs4149570) (OR: 1.92, 95% CI: 1.02‐3.60, P = 0.04), IL18(rs187238) (OR: 1.35, 95% CI: 1.00‐1.82, P = 0.05), and JAK2(rs12343867) (OR: 1.35, 95% CI: 1.02‐1.78, P = 0.03)), UC (TLR2(rs11938228) (OR: 0.55, 95% CI: 0.33‐0.92, P = 0.02), TLR4(rs5030728) (OR: 2.23, 95% CI: 1.24‐4.01, P = 0.01) and (rs1554973) (OR: 0.49, 95% CI: 0.27‐0.90, P = 0.02), NFKBIA(rs696) (OR: 1.45, 95% CI: 1.06‐2.00, P = 0.02), and NLRP3(rs4612666) (OR: 0.63, 95% CI: 0.44‐0.91, P = 0.01)) or in the combined cohort of patient with CD and UC (IBD) (TLR4(rs5030728) (OR: 1.46, 95% CI: 1.01‐2.11, P = 0.04) and (rs1554973)(OR: 0.80, 95% CI: 0.65‐0.98, P = 0.03), NFKBIA(rs696) (OR: 1.25, 95% CI: 1.01‐1.54, P = 0.04), NLRP3(rs4612666) (OR: 0.73, 95% CI: 0.57‐0.95, P = 0.02), IL1RN(rs4251961) (OR: 0.81, 95% CI: 0.66‐1.00, P = 0.05), IL18(rs1946518) (OR: 1.24, 95% CI: 1.01‐1.53, P = 0.04), and JAK2(rs12343867) (OR: 1.24, 95% CI: 1.01‐1.53, P = 0.04)).ConclusionsThe results support that polymorphisms in genes involved in the regulation of the NFκB pathway (TLR2, TLR4, and NFKBIA), the TNF‐α signalling pathway (TNFRSF1A), and other cytokine pathways (NLRP3, IL1RN, IL18, and JAK2) were associated with response to anti‐TNF therapy. Our multi‐SNP model predicted response rate of more than 82% (in 9% of the CD patients) and 75% (in 15% of the UC patients), compared to 71% and 64% in all CD and UC patients, respectively. More studies are warranted to predict response for use in the clinic.
  • Access State: Open Access