Background: Accumulating data support a protective role of Helicobacter pylori against inflammatory bowel diseases (IBD), which might be mediated by strain-specific constituents, specifically cagA expression. Aim:To perform a systematic review and meta-analysis to more clearly define the association between CagA seropositivity and IBD. Methods:We identified comparative studies that included sufficient detail to determine the odds or risk of IBD, Crohn's disease (CD) or ulcerative colitis (UC) amongst individuals with vs without evidence of cagA expression (eg CagA seropositivity).Estimates were pooled using a random effects model. Results:Three clinical studies met inclusion criteria. cagA expression was represented by CagA seropositivity in all studies. Compared to CagA seronegativity overall, CagA seropositivity was associated with lower odds of IBD (OR 0.31, 95% CI 0.21-0.44) and CD (OR 0.25, 95% CI 0.17-0.38), and statistically nonsignificant lower odds for UC (OR 0.68, 95% CI 0.35-1.32). Similarly, compared to H pylori non-exposed individuals, H pylori exposed, CagA seropositive individuals had lower odds of IBD (OR 0.26, 95% CI 0.16-0.41) and CD (OR 0.23, 95% CI 0.15-0.35), but not UC (OR 0.66, 0.34-1.27).However, there was no significant difference in the odds of IBD, CD or UC between H pylori exposed, CagA seronegative and H pylori non-exposed individuals. Conclusion:We found evidence for a significant association between CagA seropositive H pylori exposure and reduced odds of IBD, particularly CD, but not for CagA seronegative H pylori exposure. Additional studies are needed to confirm these findings and define underlying mechanisms. S U PP O RTI N G I N FO R M ATI O NAdditional supporting information will be found online in the Supporting Information section at the end of the article.How to cite this article: Tepler A, Narula N, Peek RM Jr, et al. Systematic review with meta-analysis: association betweenHelicobacter pylori CagA seropositivity and odds of inflammatory bowel disease. Aliment Pharmacol Ther.

Background & Aims: Previous or current infection with Helicobacter pylori (exposure) has been reported to protect against eosinophilic esophagitis (EoE), perhaps due to H pylori -induced immunomodulation. However, findings vary. We performed a systematic review and meta-analysis of comparative studies to more clearly define the association between H pylori exposure and EoE. Methods: We searched 4 large databases to identify comparative clinical studies that included sufficient detail to determine the odds or risk of EoE (primary outcome) or esophageal eosinophilia (secondary outcome) among individuals exposed to H pylori (exposed) vs individuals who were tested and found to be unexposed. Estimates were pooled using a random-effects model. Meta-regression and sensitivity analyses were planned a priori. Studies were evaluated for quality, risk of bias, publication bias, and heterogeneity. Results: We analyzed 11 observational studies comprising data on 377,795 individuals worldwide. H pylori exposure vs non-exposure was associated with a 37% reduction in odds of EoE (odds ratio [OR], 0.63; 95% CI, 0.51–0.78) and a 38% reduction in odds of esophageal eosinophilia (OR, 0.62; 95% CI, 0.52–0.76). Fewer prospective studies found a significant association between H pylori exposure and EoE ( P =.06) than retrospective studies. Effect estimates were not affected by study location, whether the studies were performed in pediatric or adult populations, time period (before vs after 2007), or prevalence of H pylori in the study population. Conclusions: In a comprehensive meta-analysis, we found evidence for a significant association between H pylori exposure and reduced odds of EoE. Studies are needed to determine the mechanisms of this association.

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Background Gender-based differences are reported in inflammatory bowel diseases (IBD) pathogenesis, but their impacts on IBD outcomes are not well known. We determined gender-based differences in response to treatment with tumor necrosis factor inhibitor (TNFi) therapies in individuals with ulcerative colitis (UC). Methods We used the Yale University Open Data Access (YODA) platform to abstract individual participant data from randomized clinical trials to study infliximab and golimumab as induction and maintenance therapies in moderately to severely active UC. Using multivariable logistic regression, we examined associations between gender and the endpoints of clinical remission, mucosal healing, and clinical response for each study individually and in a meta-analysis. Results Of 1639 patients included in induction trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment—Subcutaneous [PURSUIT-SC], active ulcerative colitis trials [ACT] 1 and 2) and 1280 patients included in maintenance trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment—Maintenance [PURSUIT-IM], ACT 1 and 2), 696 (42.5%) and 534 (41.7%) were women, respectively. In a meta-analysis of induction trials, the adjusted odds ratios (aORs) of clinical remission (aOR, 0.55; 95% CI, 0.31–0.97), mucosal healing (aOR, 0.47; 95% CI, 0.27–0.83), and clinical response (aOR, 0.51; 95% CI, 0.29–0.90) in the treatment arm and of clinical remission in the placebo arm (aOR, 0.34; 95% CI, 0.15–0.82) were lower in men compared to women. There were no differences in outcomes by gender in the treatment and placebo arms in the meta-analysis of maintenance trials. Conclusions Men are less likely to achieve clinical remission, mucosal healing, and clinical response compared to women during induction treatment with TNFi for UC, but not during the maintenance phase. Future studies delineating the mechanisms underlying these observations would be informative.