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Genetic associations with adverse events from anti-tumor necrosis factor therapy in inflammatory bowel disease patients.


ABSTRACT: AIM:To study the type and frequency of adverse events associated with anti-tumor necrosis factor (TNF) therapy and evaluate for any serologic and genetic associations. METHODS:This study was a retrospective review of patients attending the inflammatory bowel disease (IBD) centers at Cedars-Sinai IBD Center from 2005-2016. Adverse events were identified via chart review. IBD serologies were measured by ELISA. DNA samples were genotyped at Cedars-Sinai using Illumina Infinium Immunochipv1 array per manufacturer's protocol. SNPs underwent methodological review and were evaluated using several SNP statistic parameters to ensure optimal allele-calling. Standard and rigorous QC criteria were applied to the genetic data, which was generated using immunochip. Genetic association was assessed by logistic regression after correcting for population structure. RESULTS:Altogether we identified 1258 IBD subjects exposed to anti-TNF agents in whom Immunochip data were available. 269/1258 patients (21%) were found to have adverse events to an anti-TNF-? agent that required the therapy to be discontinued. 25% of women compared to 17% of men experienced an adverse event. All adverse events resolved after discontinuing the anti-TNF agent. In total: n = 66 (5%) infusion reactions; n = 49 (4%) allergic/serum sickness reactions; n = 19 (1.5%) lupus-like reactions, n = 52 (4%) rash, n = 18 (1.4%) infections. In Crohn's disease, IgA ASCA (P = 0.04) and IgG-ASCA (P = 0.02) levels were also lower in patients with any adverse events, and anti-I2 level in ulcerative colitis was significantly associated with infusion reactions (P = 0.008). The logistic regression/human annotation and network analyses performed on the Immunochip data implicated the following five signaling pathways: JAK-STAT (Janus Kinase-signal transducer and activator of transcription), measles, IBD, cytokine-cytokine receptor interaction, and toxoplasmosis for any adverse event. CONCLUSION:Our study shows 1 in 5 IBD patients experience an adverse event to anti-TNF therapy with novel serologic, genetic , and pathways associations.

SUBMITTER: Lew D 

PROVIDER: S-EPMC5677193 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Genetic associations with adverse events from anti-tumor necrosis factor therapy in inflammatory bowel disease patients.

Lew Daniel D   Yoon Soon Man SM   Yan Xiaofei X   Robbins Lori L   Haritunians Talin T   Liu Zhenqiu Z   Li Dalin D   McGovern Dermot Pb DP  

World journal of gastroenterology 20171001 40


<h4>Aim</h4>To study the type and frequency of adverse events associated with anti-tumor necrosis factor (TNF) therapy and evaluate for any serologic and genetic associations.<h4>Methods</h4>This study was a retrospective review of patients attending the inflammatory bowel disease (IBD) centers at Cedars-Sinai IBD Center from 2005-2016. Adverse events were identified <i>via</i> chart review. IBD serologies were measured by ELISA. DNA samples were genotyped at Cedars-Sinai using Illumina Infinium  ...[more]

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