Paternal Disease Activity Is Associated With Difficulty in Conception Among Men With Inflammatory Bowel Diseases

The impact of inflammatory bowel disease (IBD) activity and treatment on fertility and pregnancy outcomes is important for men and women. In women, remission at conception determines better pregnancy outcomes, and most maternal IBD medication exposures are safe. In contrast, less is known about the impact of paternal disease activity and medication use on fertility and pregnancy outcomes in men with IBD

Vedolizumab Is Associated With a Lower Risk of Serious Infections Than Anti-Tumor Necrosis Factor Agents in Older Adults

Background & Aims: Despite the increased numbers of older adults with inflammatory bowel diseases (IBDs), there are few studies regarding the safety and effectiveness of IBD treatments in older adults. The aim of this study was to compare the safety and effectiveness of anti–tumor necrosis factor (TNF)-α agents and vedolizumab in older adults with IBD. Methods: We conducted a retrospective cohort study using an active comparator, new-user design for adults age 65 years and older with IBD initiating anti–TNF-α agents and vedolizumab in the Medicare claims database from 2014 to 2017. The primary safety outcome was infection-related hospitalization (excluding intra-abdominal and perianal abscesses). Co-primary outcomes to estimate effectiveness were IBD-related hospitalization, IBD-related surgery, and new corticosteroid use 60 days or more after biologic initiation. We performed propensity score weighting to control for confounding and estimated adjusted hazard ratios and 95% confidence intervals using standardized morbidity ratio–weighted variables. Results: We identified 1152 anti–TNF-α new users and 480 vedolizumab new users. The median age was 71 years in both cohorts and 11% were age 80 years or older. Crohn's disease patients comprised 54% of the anti–TNF-α cohort and 57% of the vedolizumab cohort. There was no significant difference in demographics, health care utilization, or frailty in both cohorts. More than half of both cohorts had a Charlson comorbidity index of 2 or higher. Vedolizumab users had a decreased risk of infection-related hospitalization (adjusted hazard ratio, 0.47; 95% confidence interval, 0.25–0.86). There was no significant difference in the outcomes approximating effectiveness. Conclusions: Older IBD patients treated with vedolizumab had a lower risk of infection-related hospitalization compared with those initiating anti-TNFs. We observed no difference in effectiveness defined by hospitalizations, surgery, or new corticosteroid use

Asians Have More Perianal Crohn Disease and Ocular Manifestations Compared with White Americans

Background: Inflammatory bowel disease (IBD) is increasing in Asians. We sought to better understand differences in IBD between Asians and whites in the United States (US). Methods: We used data from the Sinai-Helmsley Alliance for Research Excellence cohort to assess disease characteristics for US-born Asians, Asian immigrants, and whites. We used bivariate analyses to describe clinical characteristics by race. We used logistic regression to determine baseline odds of immunosuppression and binomial regression to estimate risk ratios for worsening disease at follow-up. Results: We included 5,223 whites, 35 US-born Asians, and 81 Asian immigrants. Crohn disease (CD) was present in 64% of whites, 40% of US-born Asians, and 51% of Asian immigrants. At baseline, 58% of whites, 62% of US-born Asians, and 67% of Asian immigrants were in remission by disease activity index score (p = 0.238). There were no significant differences in CD location and behavior or ulcerative colitis extent. Asians had significantly more perianal disease than whites (33 vs. 18%, p = 0.007). Asians were more likely to have ocular manifestations than whites (3.4 vs. 0.7%, p = 0.022). Asians were also significantly less likely to be depressed than whites (25 vs. 35%, p = 0.022). Adjusting for confounders, Asians had half the odds of being treated with biologics compared with whites (OR: 0.45, 95% CI: 0.30-0.67). Adjusting for disease behavior and remission status, there were no differences in IBD-related surgery or hospitalization, new biologic or steroid prescription, or relapse rates between Asians and whites at follow-up. Conclusion: Asians are more likely to have perianal disease and ocular extraintestinal manifestations. After controlling for confounders, Asians were less likely to be treated with biologic agents. Despite this, there were no significant differences in outcomes over time between Asians and whites. Differences in disease phenotypes in Asians may reflect differences in genetics

Management of Patients With Crohn's Disease and Ulcerative Colitis During the Coronavirus Disease-2019 Pandemic: Results of an International Meeting

The International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) is the only global organization devoted to the study of and management of the inflammatory bowel diseases (IBDs), namely, Crohn?s disease and ulcerative colitis. Membership is composed of physician-scientists who have established expertise in these diseases. The organization hosts an annual meeting and a number of working groups addressing issues of the epidemiology of IBD, diet and nutrition, and the development and use of treatments for IBD. There are currently 89 members of IOIBD representing 26 different countries. The organization has taken particular interest in the coronavirus disease-2019 (COVID-19) pandemic and how it may affect the IBD patient population. This document summarizes the results of 2 recent virtual meetings of the group and subsequent expert guidance for patients and providers

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn's disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes.

GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach

High school diet and risk of Crohn's disease and ulcerative colitis

BACKGROUND: Diet may play an important role in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC); yet, there are few prospective studies of dietary factors. None have examined the association between adolescent diet and risk of inflammatory bowel diseases (CD and UC). METHODS: This study included women enrolled in Nurses' Health Study II who completed a validated high school dietary questionnaire in 1998. We examined the effect of dietary patterns (prudent or Western diet) and individual components of each patterns. We documented incident cases of CD and UC through 2011 based on physician review of medical records and used Cox proportional hazards models adjusting for confounders to estimate hazard ratios and confidence intervals for CD and UC. RESULTS: Over 763,229 person-years of follow-up, we identified 70 incident cases of CD and 103 cases of UC. Compared with women in the lowest quartile of a prudent diet score (characterized by greater intake of fruits, vegetables, and fish), women in the highest quartile had a 53% lower risk of CD (hazard ratio, 0.47; 95% confidence interval, 0.23-0.98; Ptrend = 0.04). Specifically, greater intake of fish (Ptrend = 0.01) and fiber (Ptrend = 0.06) were associated with lower risk of CD. In contrast, Western diet score was not associated with risk of CD. Neither dietary patterns nor individual food or nutrient groups was associated with UC. CONCLUSIONS: Adolescent diet is associated with risk of CD, but not UC, offering insights into disease pathogenesis