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Systematic review and meta-analysis on the association of tuberculosis in Crohn's disease patients treated with tumor necrosis factor-? inhibitors (Anti-TNF?).

ABSTRACT: AIM:To perform a meta-analysis on the risk of developing Mycobacterium tuberculosis (TB) infection in Crohn's disease (CD) patients treated with tumor necrosis factor-alpha (TNF?) inhibitors. METHODS:A meta-analysis of randomized, double-blind, placebo-controlled trials of TNF? inhibitors for treatment of CD in adults was conducted. Arcsine transformation of TB incidence was performed to estimate risk difference. A novel epidemiologically-based correction (EBC) enabling inclusions of studies reporting no TB infection cases in placebo and treatment groups was developed to estimate relative odds. RESULTS:Twenty-three clinical trial studies were identified, including 5669 patients. Six TB infection cases were reported across 5 studies, all from patients receiving TNF? inhibitors. Eighteen studies reported no TB infection cases in placebo and TNF? inhibitor treatment arms. TB infection risk was significantly increased among patients receiving TNF? inhibitors, with a risk difference of 0.028 (95%CI: 0.0011-0.055). The odds ratio was 4.85 (95%CI: 1.02-22.99) with EBC and 5.85 (95%CI: 1.13-30.38) without EBC. CONCLUSION:The risk of TB infection is higher among CD patients receiving TNF? inhibitors. Understanding the immunopathogenesis of CD is crucial, since using TNF? inhibitors in these patients could favor mycobacterial infections, particularly Mycobacterium avium subspecies paratuberculosis, which ultimately could worsen their clinical condition.

SUBMITTER: Cao BL

PROVIDER: S-EPMC6034143 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Systematic review and meta-analysis on the association of tuberculosis in Crohn's disease patients treated with tumor necrosis factor-α inhibitors (Anti-TNFα).

Cao Brent L BL Qasem Ahmad A Sharp Robert C RC Abdelli Latifa S LS Naser Saleh A SA

World journal of gastroenterology 20180701 25

<h4>Aim</h4>To perform a meta-analysis on the risk of developing <i>Mycobacterium tuberculosis</i> (TB) infection in Crohn's disease (CD) patients treated with tumor necrosis factor-alpha (TNFα) inhibitors.<h4>Methods</h4>A meta-analysis of randomized, double-blind, placebo-controlled trials of TNFα inhibitors for treatment of CD in adults was conducted. Arcsine transformation of TB incidence was performed to estimate risk difference. A novel epidemiologically-based correction (EBC) enabling inc ...[more]

PMID: 29991880

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Project description:To investigate genetic factors that might help define which Crohn's disease (CD) patients are likely to benefit from anti-tumor necrosis factor (TNF) therapy.This was a prospective cohort study. Patients were recruited from a university digestive disease practice database. We included CD patients who received anti-TNF therapy, had available medical records (with information on treatment duration and efficacy) and who consented to participation. Patients with allergic reactions were excluded. Patients were grouped as ever-responders or non-responders. Genomic DNA was extracted from peripheral blood, and 7 single nucleotide polymorphisms (SNPs) were assessed. The main outcome measure (following exposure to the drug) was response to therapy. The patient genotypes were assessed as the predictors of outcome. Possible confounders and effect modifiers included age, gender, race, and socioeconomic status disease, as well as disease characteristics (such as Montreal criteria).121 patients were included. Twenty-one were non-responders, and 100 were ever-responders. Fas ligand SNP (rs763110) genotype frequencies, TNF gene -308 SNP (rs1800629) genotype frequencies, and their combination, were significantly different between groups on multivariable analysis controlling for Montreal disease behavior and perianal disease. The odds of a patient with a Fas ligand CC genotype being a non-responder were four-fold higher as compared to a TC or TT genotype (P = 0.009, OR = 4.30, 95%CI: 1.45-12.80). The presence of the A (minor) TNF gene -308 allele correlated with three-fold higher odds of being a non-responder (P = 0.049, OR = 2.88, 95%CI: 1.01-8.22). Patients with the combination of the Fas ligand CC genotype and the TNF -308 A allele had nearly five-fold higher odds of being a non-responder (P = 0.015, OR = 4.76, 95%CI: 1.35-16.77). No difference was seen for the remaining SNPs.The Fas-ligand SNP and TNF gene -308 SNP are associated with anti-TNF treatment response in CD and may help select patients likely to benefit from therapy.

Dataset Information

Systematic review and meta-analysis on the association of tuberculosis in Crohn's disease patients treated with tumor necrosis factor-? inhibitors (Anti-TNF?).

Publications

Systematic review and meta-analysis on the association of tuberculosis in Crohn's disease patients treated with tumor necrosis factor-α inhibitors (Anti-TNFα).

Similar Datasets

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