Highlights d 51 cell subsets in colon mucosa of 18 ulcerative colitis and 12 healthy individuals d M-like cells, inflammatory monocytes and fibroblasts, and CD8 + IL-17 + T cells expand in disease d Oncostatin M circuit in inflammatory monocytes and fibroblasts may affect drug response d Co-expression of genes within cells allows inference of causal genes across risk loci

Background Inflammatory bowel diseases lead to progressive bowel damage and need for surgery. While the increase in prevalence of other immune-mediated diseases in IBD is well recognized, the impact of this on the natural history of IBD is unknown. Aim To determine the impact of concomitant immune-mediate disease on phenotypes and outcomes in IBD Methods Patients with IBD enrolled in a prospective registry were queried about the presence of other immune-mediated diseases, defined as those where immune dysregulation plays a role in pathogenesis. Demographics and disease-related information were obtained. Subjects also completed measures of quality of life. Multivariable regression models compared disease phenotype and outcomes of IBD patients with and without other immune-mediated diseases. Results The cohort included 2,145 IBD patients among whom 458 (21%) had another immune-mediated disease. There was no difference in CD phenotype between the two groups. UC patients were more likely to have pancolitis in the presence of another immune-mediated disease (62%) compared to those without (52%, p=0.02). IBD patients with another immune-mediated disease had higher rates of needing anti-TNF biologics (Odds ratio (OR) 1.31, 95% CI 1.05–1.63) and surgery (OR 1.26, 95% CI 0.99–1.61). The presence of another immune-mediated disease was also associated with lower disease-specific and general physical quality of life. Conclusions The presence of another immune-mediated disease in IBD patients was associated with higher likelihood of pancolonic involvement in UC and a modest increase in need for IBD-related surgery and anti-TNF biologic therapy. Such patients also experienced worse quality of life.

Introduction Poor sleep, depression, and anxiety are common in patients with inflammatory bowel diseases (IBD) and associated with increased risk of relapse and poor outcomes. The effectiveness of therapies in improving such psychosocial outcomes is unclear but is an important question to examine with increasing selectivity of therapeutic agents. Methods This prospective cohort enrolled patients with moderate-to-severe CD or UC starting biologic therapy with vedolizumab or anti-tumor necrosis factor α agents (anti-TNF). Sleep quality, depression, and anxiety were measured using validated short-form NIH PROMIS questionnaires assessing sleep and mood quality over the past 7 days. Disease activity was assessed using validated indices. Improvement in sleep and mood scores from baseline was assessed, and regression models were used to identify determinants of sleep quality. Results Our study included 160 patients with IBD (49 anti-TNF, 111 Vedolizumab) among whom half were women and the mean age was 40.2 years. In the combined cohort, we observed a statistically significant and meaningful decrease in mean scores from baseline (52.8) by week 6 (49.8, p = 0.002). Among vedolizumab users, sleep T-score improved from baseline (53.6) by week 6 (50.7) and persisted through week 54 (46.5, p = 0.009). Parallel reductions in depression and anxiety were also noted (p < 0.05 by week 6). We observed no difference in improvement in sleep, depression, and anxiety between vedolizumab and anti-TNF use at week 6. Conclusions Both vedolizumab and anti-TNF biologic therapies were associated with improvement in sleep and mood quality in IBD.

Introduction The burden of inflammatory bowel disease (IBD) in the older population is increasing. Older-onset disease is associated with reduced use of immunosuppressive medications. In addition, older patients may be more vulnerable to the effect of disease-related symptoms, and consequently may experience worse health-related quality of life (HRQoL) compared to younger patients. Methods This prospective study included a cohort of patients with Crohn’s disease (CD) and ulcerative colitis (UC) recruited from a single center. All patients completed the short inflammatory bowel disease questionnaire (SIBDQ) and the short form-12 questionnaire (SF-12) yielding general physical (PCS) and mental component scale subscores (MCS). Patients older than age 60 years were compared to those younger than age 60 using multivariable regression analysis. Results Our study included 1,607 patients, among whom 186 were older than age 60 at the time of assessment. Older patients were more likely to have isolated colonic disease and less likely to use immunosuppressive therapy. On multivariable analysis, older IBD patients had higher SIBDQ (2.34, 95% confidence interval (CI) 0.82 – 3.87) and SF12 mental subscores (3.78, 95% CI 2.26 – 5.30) but lower physical HRQoL (−1.80, 95% CI −3.21 to −0.38). There was no difference in the SIBDQ and PCS scores between older patients with newly diagnosed IBD or with established disease. Conclusion Older age was associated with modestly higher SIBDQ and mental HRQoL but lower physical HRQoL. Comprehensive care of the older IBD patient should include assessment of factors impairing physical quality of life to ensure appropriate interventions.

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