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The rising incidence of inflammatory bowel disease in regions undergoing Westernization has coincided with the increase in ultra-processed food (UPF) consumption over the past few decades. We aimed to examine the association between consumption of UPFs and the risk of Crohn's disease (CD) and ulcerative colitis (UC). We performed a prospective cohort study of 3 nationwide cohorts of health professionals in the United States—the Nurses' Health Study (1986–2014), the Nurses' Health Study II (1991–2017), and the Health Professionals Follow-up Study (1986–2012). We employed Cox proportional hazards models with adjustment for confounders to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for CD and UC according to self-reported consumption of UPFs. The study included 245,112 participants. Over 5,468,444 person-years of follow-up, we documented 369 incident cases of CD and 488 incident cases of UC. The median age at diagnosis was 56 years (range, 29–85 years). Compared with participants in the lowest quartile of simple updated UPF consumption, those in the highest quartile had a significantly increased risk of CD (HR, 1.70; 95% CI, 1.23–2.35; P trend =.0008). Among different UPF subgroups, ultra-processed breads and breakfast foods; frozen or shelf-stable ready-to-eat/heat meals; and sauces, cheeses, spreads, and gravies showed the strongest positive associations with CD risk (HR per 1 standard deviation increase in intake, 1.18 [95% CI, 1.07–1.29], 1.11 [95% CI, 1.01–1.22], and 1.14 [95% CI, 1.02–1.27], respectively). There was no consistent association between UPF intake and UC risk. Higher UPF intake was associated with an increased risk of incident CD. Further studies are needed to identify specific contributory dietary components. [Display omitted] [ABSTRACT FROM AUTHOR]

Although colonoscopies for dysplasia surveillance are standard of care in patients with long-standing ulcerative colitis (UC), there is a paucity of data on the yield of surveillance colonoscopies in those older than 75 years of age. We conducted a multicenter retrospective cohort study including patients with UC who underwent ≥1 colonoscopy at age ≥75 years. The primary outcome was diagnosis of dysplasia (visible or random) and colorectal cancer. Multivariable regression adjusted for relevant confounders examined the predictors of polypoid or non-polypoid dysplasia or colorectal cancer. The primary cohort included 211 patients with UC who underwent 635 colonoscopies after age ≥75 years. A total of 83 patients (39.3%) patients had dysplasia or cancer detected. Among colonoscopies, 123 (19.4%) identified visible dysplasia, 23 (3.6%) had random dysplasia (1 high-grade dysplasia found in each group, respectively), and 5 (0.8%) had colon cancer. In multivariable analysis, prior adenoma or colon cancer below age 75 tears (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.07–3.96), flat dysplasia before 75 years (OR, 2.78; 95% CI, 1.05–7.44), and older age (80-84 years (OR, 2.29; 95% CI, 1.20–4.38), ≥85 years (OR, 3.54; 95% CI, 1.27–9.82) were associated with detection of dysplasia or cancer. Only 1 patient was noted to have a procedure-related complication. Patients with long-standing UC without prior dysplasia may have a low yield on continued endoscopic surveillance at age ≥75 years. A targeted approach to surveillance may be appropriate in older individuals with UC. [ABSTRACT FROM AUTHOR]

Treatment of patients with inflammatory bowel diseases (IBD; Crohn's disease (CD), ulcerative colitis (UC) who have a prior history of cancer pose a unique challenge. The impact of Vedolizumab (VDZ) on the risk of new or recurrent cancers in patients with a previous malignancy is unknown. This was a retrospective study of patients with IBD with a history of current or prior cancer who were subsequently initiated on VDZ, tumor necrosis factor α antagonists (anti-TNF), or had no immunosuppressive therapy after the index cancer diagnosis. The occurrence of a new primary cancer or recurrent cancer was ascertained on follow-up. Multivariable Cox-proportional hazard models were used to determine the independent effect of post-cancer treatment on new/recurrent cancer. The study included 96 patients exposed to VDZ after a prior diagnosis of cancer who were compared to 184 and 183 patients exposed to anti-TNF or no immunosuppressive therapy, respectively. The most common primary cancer were solid tumors (50%). Over a median of 6.2 person-years of follow-up, 18 patients on VDZ developed new (7) or recurrent (11) cancer corresponding to a rate of 22 per 1000 person-years after cancer diagnosis. In a multivariable Cox-model, after adjusting for confounders, there was no increase in the risk of new or recurrent cancer with VDZ (HR 1.38 95% CI 0.38 – 1.36) or anti-TNF therapy (HR 1.03, 95% CI 0.65 – 1.64), when compared to no IS. Neither Vedolizumab nor TNF-antagonists were associated with increased risk of new or recurrent cancers in patients with prior malignancy. [ABSTRACT FROM AUTHOR]

There are limited data on the safety of immunosuppressive therapy use in individuals with immune-mediated diseases with a history of malignancy, particularly with newer biologic and small-molecule treatments. We performed a systematic search of PubMed and Embase databases to identify studies examining the impact of immunosuppressive therapies on cancer recurrence across several immune-mediated diseases. Studies were pooled together using random-effects meta-analysis and stratified by type of treatment. Primary outcome was occurrence of incident cancers, defined as new or recurrent. Our meta-analysis included 31 studies (17 inflammatory bowel disease, 14 rheumatoid arthritis, 2 psoriasis, and 1 ankylosing spondylitis) contributing 24,328 persons and 85,784 person-years (p-y) of follow-up evaluation. Rates of cancer recurrence were similar among individuals not on immunosuppression (IS) (1627 incident cancers, 43,765 p-y; 35 per 1000 p-y; 95% CI, 27–43), receiving an anti–tumor necrosis factor (571 incident cancers, 17,772 p-y; 32 per 1000 p-y; 95% CI, 25–38), immunomodulators (1104 incident cancers, 17,018 p-y; 46 per 1000 p-y; 95% CI, 31–61), combination immunosuppression (179 incident cancers, 2659 p-y; 56 per 1000 p-y; 95% CI, 31–81). Patients receiving ustekinumab (5 incident cancers, 213 p-y; 21 per 1000 p-y; 95% CI, 0–44) and vedolizumab (37 incident cancers, 1951 p-y; 16 per 1000 p-y; 95% CI, 5–26) had numerically lower rates of cancer. There were no studies on Janus kinase inhibitors. Stratification of studies by timing of immunosuppression initiation did not reveal a medication effect based on early (<5 years) or delayed treatment initiation. In patients with immune-mediated diseases and a history of malignancy, we observed similar rates of cancer recurrence in those on no immunosuppression compared with different immunosuppressive treatments. [Display omitted] [ABSTRACT FROM AUTHOR]

Randomized controlled trials (RCTs) are an important mode of access to treatments for patients with inflammatory bowel diseases (IBDs) (eg, Crohn's disease [CD], ulcerative colitis [UC]), and a critical step in the regulatory process toward the approval of new therapies. Prior studies examining disparities in RCT participation for patients with IBD have importantly focused on racial and age-related disparities.1,2 Lack of geographic access to trials may be an important barrier to participation and a source of inequity. The aim of our study was to geographically map access to phase 3 clinical trials in IBD within the United States, and identify the impact of rural residence and socioeconomic status on access to trials. [ABSTRACT FROM AUTHOR]

Crohn's disease and ulcerative colitis have emerged as global diseases. They affect over 2 million individuals in the North America, 3.2 million in Europe, and millions more worldwide. The recent decades have been characterized by several important changes in the epidemiology of these diseases, in particularly an increasing incidence rates in newly industrialized countries experiencing a westernization of lifestyle. While rates of surgery have experienced a temporal decline attributable in part to increasing availability of medical treatments, earlier initiation of effective therapy, and changes in clinical practice, the healthcare costs associated with these diseases have continued to increase, in part due to costly therapies. Robust epidemiologic and experimental studies have defined the role of the external environment and microbiome on disease pathogenesis and have offered opportunities for disease prevention by modifying such factors. We propose several important steps that are necessary to provide globally sustainable inflammatory bowel disease care in the 21st century. [ABSTRACT FROM AUTHOR]

It is unclear whether ulcerative colitis (UC) is a progressive disease similar to Crohn's disease (CD). Patients with UC often are undertreated because of the possibility of curative colectomy and the perception that the disease burden is lower than that of CD. We discuss findings from studies that aimed to determine whether UC and CD have the same disease burden and should be treated in the same intensive way. We discuss the similarities between CD and UC, including effects on quality of life, long-term complications, strictures, increased risk of cancer, pseudopolyps, functional abnormalities, and anorectal dysfunction. Contrary to the generally accepted idea, surgery cannot cure UC. Postoperative complications, especially pouchitis and fecal incontinence, affect more than one third of patients. CD and UC each pose substantial economic burdens. Monitoring, treatments, and goals of therapy are similar for all inflammatory bowel diseases. Earlier initiation of disease-modifying drugs might reduce the progression of UC and reduce its burden after surgery, although UC might not cause the irreversible damage observed in patients with CD. [ABSTRACT FROM AUTHOR]

The evolution of complicated pediatric Crohn's disease (CD) in the era of anti–tumor necrosis factor (aTNF) therapy continues to be described. Because CD progresses from inflammatory to stricturing (B2) and penetrating (B3) disease behaviors in a subset of patients, we aimed to understand the risk of developing complicated disease behavior or undergoing surgery in relation to aTNF timing and body mass index z-score (BMIz) normalization. Multicenter, 5-year longitudinal data from 1075 newly diagnosed CD patients were analyzed. Descriptive statistics, univariate and stepwise multivariate Cox proportional hazard regression (CPHR), and log-rank analyses were performed for risk of surgery and complicated disease behaviors. Differential gene expression from ileal bulk RNA sequencing was correlated with outcomes. Stricturing complications had the largest increase: from 2.98% to 10.60% over 5 years. Multivariate CPHR showed aTNF exposure within 3 months from diagnosis (hazard ratio [HR], 0.33; 95% CI, 0.15–0.71) and baseline L2 disease (HR, 0.29; 95% CI, 0.09–0.92) to be associated with reduced B1 to B2 progression. For children with a low BMIz at diagnosis (n = 294), multivariate CPHR showed BMIz normalization within 6 months of diagnosis (HR, 0.47; 95% CI, 0.26–0.85) and 5-aminosalicyclic acid exposure (HR, 0.32; 95% CI, 0.13–0.81) were associated with a decreased risk for surgery while B2 (HR, 4.20; 95% CI, 1.66–10.65) and B2+B3 (HR, 8.24; 95% CI, 1.08–62.83) at diagnosis increased surgery risk. Patients without BMIz normalization were enriched for genes in cytokine production and inflammation. aTNF exposure up to 3 months from diagnosis may reduce B2 progression. In addition, lack of BMIz normalization within 6 months of diagnosis is associated with increased surgery risk and a proinflammatory transcriptomic profile. [ABSTRACT FROM AUTHOR]

Several studies have been published on the association between food processing and risks of Crohn's disease (CD) and ulcerative colitis (UC), with some variability in results. We performed a systematic literature review and meta-analysis to study this association. From PubMed, Medline, and Embase until October 2022, we identified cohort studies that studied the association between food processing and the risk of CD or UC. Risk of bias of the included studies was assessed by the Newcastle-Ottawa scale. We computed pooled hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects meta-analysis based on estimates and standard errors. A total of 1,068,425 participants were included (13,594,422 person-years) among 5 cohort studies published between 2020 and 2022. Four of the 5 included studies were scored as high quality. The average age of participants ranged from 43 to 56 years; 55%–83% were female. During follow-up, 916 participants developed CD, and 1934 developed UC. There was an increased risk for development of CD for participants with higher consumption of ultra-processed foods compared with those with lower consumption (HR, 1.71; 95% CI, 1.37–2.14; I2 = 0%) and a lower risk of CD for participants with higher consumption of unprocessed/minimally processed foods compared with those with lower consumption (HR, 0.71; 95% CI, 0.53–0.94; I2 = 11%). There was no association between risk of UC and ultra-processed foods (HR, 1.17; 95% CI, 0.86–1.61; I2 = 74%) or unprocessed/minimally processed foods (HR, 0.84; 95% CI, 0.68–1.02; I2 = 0%). Higher ultra-processed food and lower unprocessed/minimally processed food intakes are associated with higher risk of CD but not UC. [Display omitted] [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) and ulcerative colitis (UC) are heterogeneous. With availability of therapeutic classes with distinct immunologic mechanisms of action, it has become imperative to identify markers that predict likelihood of response to each drug class. However, robust development of such tools has been challenging because of need for large prospective cohorts with systematic and careful assessment of treatment response using validated indices. Most hospitals in the United States use electronic health records (EHRs) that warehouse a large amount of narrative (free-text) and codified (administrative) data generated during routine clinical care. These data have been used to construct virtual disease cohorts for epidemiologic research as well as for defining genetic basis of disease states or discrete laboratory values.1–3 Whether EHR-based data can be used to validate genetic associations for more nuanced outcomes such as treatment response has not been examined previously. [ABSTRACT FROM AUTHOR]

Background & Aims Inflammatory bowel diseases (IBDs) such as Crohn’s disease and ulcerative colitis are associated with an increased risk of colorectal cancer (CRC). Chemopreventive strategies have produced weak or inconsistent results. Statins have been associated inversely with sporadic CRC. We examined their role as chemopreventive agents in patients with IBD. Methods We collected data from 11,001 patients with IBD receiving care at hospitals in the Greater Boston metropolitan area from 1998 through 2010. Diagnoses of CRC were determined using validated International Classification of Diseases, 9th revision, Clinical Modification codes. Statin use before diagnosis was assessed through analysis of electronic prescriptions. We performed multivariate logistic regression analyses, adjusting for potential confounders including primary sclerosing cholangitis, smoking, increased levels of inflammation markers, and CRC screening practices to identify an independent association between statin use and CRC. We performed sensitivity analyses using propensity score adjustment and variation in the definition of statin use. Results In our cohort, 1376 of the patients (12.5%) received 1 or more prescriptions for a statin. Patients using statins were more likely to be older, male, white, smokers, and have greater comorbidity than nonusers. Over a follow-up period of 9 years, 2% of statin users developed CRC compared with 3% of nonusers (age-adjusted odds ratio, 0.35; 95% confidence interval, 0.24–0.53). On multivariate analysis, statin use remained independently and inversely associated with CRC (odds ratio, 0.42; 95% confidence interval, 0.28–0.62). Our findings were robust on a variety of sensitivity and subgroup analyses. Conclusions Statin use was associated inversely with the risk of CRC in a large IBD cohort. Prospective studies on the role of statins as chemopreventive agents are warranted. [ABSTRACT FROM AUTHOR]

Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the Definition and endpoints for ulcerative PROCtitis in clinical TRIALs initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults. Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters. The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity was proposed. Secondary endpoints that should be evaluated include endoscopic remission, histologic remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life. In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the Definition and end points for ulcerative PROCtitis in clinical TRIALs consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials. [ABSTRACT FROM AUTHOR]

The comparative safety of therapies is important to inform relative positioning within the therapeutic algorithm. Tumor necrosis factor α antagonists (anti-TNF) are associated with an increased risk of infections. Whether there is a similar increase with ustekinumab (UST) or tofacitinib has not been established. We identified patients with Crohn's disease or ulcerative colitis from a national commercial health insurance plan in the United States between 2008 and 2019. Infectious outcomes were ascertained for patients newly initiating anti-TNF, UST, or tofacitinib therapy. Cox proportional hazards models were fit in propensity score-weighted cohorts to compare rates between patients treated with UST or tofacitinib and anti-TNF therapy. Our study included 19,096, 2420, and 305 patients with inflammatory bowel disease initiating anti-TNF, UST, and tofacitinib therapy, respectively. Over follow-up on-treatment, 7% and 44% of anti-TNF patients had infection-related hospitalizations and developed infections, respectively, compared with 4% and 32% of UST patients and 6% and 41% of tofacitinib patients. In the weighted Cox analysis, UST was associated with a significantly lower risk of infection (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.86–0.99) compared with anti-TNF therapy. There was a trend towards a reduction in infection-related hospitalizations (HR, 0.84; 95% CI, 0.66–1.03). The risk of infections (HR, 0.97; 95% CI, 0.75–1.24) or infection-related hospitalizations (HR, 0.59; 95% CI, 0.27–1.05) were similar between patients on tofacitinib and anti-TNF. UST is associated with reduced risk of infections compared to anti-TNF biologics in inflammatory bowel disease, whereas no difference was observed between tofacitinib and anti-TNF therapy. [ABSTRACT FROM AUTHOR]

We examined whether relationships between known risk factors for Crohn's disease (CD) and ulcerative colitis (UC) differ according to disease phenotype, defined by Montreal classification, at the time of diagnosis. We performed a prospective cohort study of 208,070 adults from the Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (HPFS). Dietary, lifestyle, and medical data were obtained at baseline and every 2–4 years. We confirmed cases of inflammatory bowel disease (IBD) and their phenotypes via medical record review. We tested for heterogeneity across CD subtypes using the likelihood ratio test and for linear heterogeneity across UC subtypes using the meta-regression method. We ascertained 346 cases of CD and 456 cases of UC over 5,117,021 person-years of follow-up (1986–2016 for NHS and HPFS; 1991–2017 for NHSII). Fiber intake was associated with decreased risk for ileocolonic but not ileal or colonic CD (P heterogeneity =.04). Physical activity was associated with decreased risk of nonstricturing and nonpenetrating CD but not of penetrating CD (P heterogeneity =.02). Higher body mass index and current smoking were associated with decreased risk of proctitis and left-sided UC but not of pan-UC (P linear heterogeneity =.004 and.02, respectively). The associations between other risk factors examined and risk of CD and UC did not differ by disease phenotype (all P heterogeneity >.06). In 3 large prospective cohorts, we observed that dietary and lifestyle risk factors for IBD may differ according to disease phenotype. These findings highlight the need for disease stratification in future epidemiologic studies. [Display omitted] [ABSTRACT FROM AUTHOR]

Sugar overconsumption is linked to a rise in the incidence of noncommunicable diseases such as diabetes, cardiovascular diseases, and cancer. This increased incidence is becoming a real public health problem that is more severe than infectious diseases, contributing to 35 million deaths annually. Excessive intake of free sugars can cause many of the same health problems as excessive alcohol consumption. Many recent international recommendations have expressed concerns about sugar consumption in Westernized societies, as current consumption levels represent quantities with no precedent during hominin evolution. In both adults and children, the World Health Organization strongly recommends reducing free sugar intake to <10% of total energy intake and suggests a further reduction to below 5%. Most studies have focused on the deleterious effects of Western dietary patterns on global health and the intestine. Whereas excessive dietary fat consumption is well studied, the specific impact of sugar is poorly described, while refined sugars represent up to 40% of caloric intake within industrialized countries. However, high sugar intake is associated with multiple tissue and organ dysfunctions. Both hyperglycemia and excessive sugar intake disrupt the intestinal barrier, thus increasing gut permeability and causing profound gut microbiota dysbiosis, which results in a disturbance in mucosal immunity that enhances infection susceptibility. This review aims to highlight the roles of different types of dietary carbohydrates and the consequences of their excessive intake for intestinal homeostasis. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]