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ObjectiveTo estimate the proportion of cases of Crohn’s disease (CD) and ulcerative colitis (UC) that could be prevented by modifiable lifestyle factors.DesignIn a prospective cohort study of US adults from the Nurses’ Health Study (NHS; n=72 290), NHSII (n=93 909) and Health Professionals Follow-up Study (HPFS; n=41 871), we created modifiable risk scores (MRS; 0–6) for CD and UC based on established lifestyle risk factors, and healthy lifestyle scores (HLS; 0–9) derived from American healthy lifestyle recommendations. We calculated the population attributable risk by comparing the incidence of CD and UC between low-risk (CD-MRS≤1, UC-MRS≤2, HLS≥7) and high-risk groups. We externally validated our findings in three European cohorts: the Swedish Mammography Cohort (n=37 275), Cohort of Swedish Men (n=40 810) and European Prospective Investigation into Cancer and Nutrition (n=404 144).ResultsOver 5 117 021 person-years of follow-up (NHS, HPFS: 1986–2016; NHSII: 1991–2017), we documented 346 CD and 456 UC cases. Adherence to a low MRS could have prevented 42.9% (95% CI 12.2% to 66.1%) of CD and 44.4% (95% CI 9.0% to 69.8%) of UC cases. Similarly, adherence to a healthy lifestyle could have prevented 61.1% (95% CI 16.8% to 84.9%) of CD and 42.2% (95% CI 1.7% to 70.9%) of UC cases. In our validation cohorts, adherence to a low MRS and healthy lifestyle could have, respectively, prevented 43.9%–51.2% and 48.8%–60.4% of CD cases and 20.6%–27.8% and 46.8%–56.3% of UC cases.ConclusionsAcross six US and European cohorts, a substantial burden of inflammatory bowel diseases risk may be preventable through lifestyle modification.

The impact of histologic inflammation on subsequent risk of acute pouchitis in patients with ulcerative colitis (UC) has not been robustly examined.We examined the association between histologic inflammation in endoscopically normal-appearing ileal pouches in patients with UC with subsequent risk of antibiotic-responsive acute pouchitis.Among 163 study patients, 53% had histologic inflammation in an endoscopically normal-appearing ileal pouch. Histologic inflammation in the pouch was associated with an increased risk of pouchitis (24.1% vs 6.8%, adjusted odds ratio 4.41, 95% confidence interval 1.48-13.20).Histologic inflammation in an endoscopically normal pouch was associated with an increased risk of acute pouchitis.

There are limited data on comparative risk of infections with various biologic agents in older adults with inflammatory bowel diseases (IBDs). We aimed to assess the comparative safety of biologic agents in older IBD patients with varying comorbidity burden.We used data from a large, national commercial insurance plan in the United States to identify patients 60 years and older with IBD who newly initiated tumor necrosis factor-α antagonists (anti-TNF), vedolizumab, or ustekinumab. Comorbidity was defined using the Charlson Comorbidity Index (CCI). Our primary outcome was infection-related hospitalizations. Cox proportional hazards models were fitted in propensity score-weighted cohorts to compare the risk of infections between the different therapeutic classes.The anti-TNF, vedolizumab, and ustekinumab cohorts included 2,369, 972, and 352 patients, respectively, with a mean age of 67 years. The overall rate of infection-related hospitalizations was similar to that of anti-TNF agents for patients initiating vedolizumab (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.84-1.04) and ustekinumab (0.92, 95% CI 0.74-1.16). Among patients with a CCI of1, both ustekinumab (HR: 0.66, 95% CI: 0.46-0.91, p-interaction0.01) and vedolizumab (HR: 0.78, 95% CI: 0.65-0.94, p-interaction: 0.02) were associated with a significantly lower rate of infection-related hospitalizations compared with anti-TNFs. No difference was found among patients with a CCI of ≤1.Among adults 60 years and older with IBD initiating biologic therapy, both vedolizumab and ustekinumab were associated with lower rates of infection-related hospitalizations than anti-TNF therapy for those with high comorbidity burden.

Environmental and lifestyle factors play an important role in the natural history of Crohn's disease and ulcerative colitis. A group of international experts from the International Organization for the Study of Inflammatory Bowel Diseases voted on a series of consensus statements to inform the management of inflammatory bowel disease (IBD). The recommendations include avoiding traditional cigarette smoking in patients with Crohn's disease or ulcerative colitis, screening for symptoms of depression, anxiety, and psychosocial stressors at diagnosis and during flares (with referral to mental health professionals when appropriate), and encouraging regular physical activity as tolerated. Patients using dietary approaches for treatment of their IBD should be encouraged to adopt diets that are best supported by evidence and involve monitoring for the objective resolution of inflammation. We recommend formal assessment for obesity and nutritional deficiencies, and patients should be encouraged to maintain a normal body-mass index. A shared decision-making approach to contraception should include the consideration of IBD-related factors, and risk factors for venous thromboembolism. Long-term or frequent use of high-dose non-steroidal anti-inflammatory drugs should be avoided. For primary prevention of disease in the offspring of patients with IBD, we recommend avoiding passive exposure to tobacco, using antibiotics judiciously, and considering breastfeeding when able.

Purpose of review In this article, we provide an overview of studies examining multiomic profiling in various clinical scenarios in the management of inflammatory bowel diseases (IBDs). Recent findings IBD arises as a result of an interplay between genetic, environmental, microbial and immunologic perturbations. The access to high throughput technology as well as the decrease in costs associated with such studies has led to a growing wealth of literature examining the utility of single or multiomic profiles in the management of IBD. Such studies have commonly examined the genome (and less frequently the epigenome), transcriptome, metabolome, proteome and the gut microbial metagenome in the context of overall IBD status or specific clinical scenarios, including the disease progression or response to treatment. The findings have provided important insight into how each of these compartments reflect underlying disease pathophysiologic processes and, in turn, can influence stratification of patients for clinical management. Summary Multiomic profiling in IBD has the potential to advance the field of personalized precision medicine in the management of IBDs.

Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a chronic, relapsing immune-mediated disease with a varying and sometimes severe disease course. IBD is often diagnosed in early adulthood and can lead to a substantial decline in quality of life. It has been suggested that patients with IBD are at increased risk of depression and anxiety, but it is still unclear to what extent these diseases co-occur and in what sequence they arise. This Review summarizes the literature on the degree of co-occurrence of IBD with depression and anxiety and the temporal relationship between these diseases. We also discuss the effect of psychological stress on the onset and course of IBD. In addition, we outline the possible mechanisms underlying the co-occurrence of IBD and depression and anxiety, which include changes in brain signalling and morphology, increases in peripheral and intracerebral pro-inflammatory cytokines, impairment of the nitric oxide pathway, changes in vagal nerve signalling, gut dysbiosis and genetics. Finally, we examine the possible effects of treatment of depression and anxiety on the risk and course of IBD, the influence of psychological interventions on IBD, and the effects of IBD treatment on psychiatric comorbidity.

Background & Aims 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). Methods 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. Results 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; Ptrend = .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. Conclusions Higher UPF intake was associated with an increased risk of incident CD. Further studies are needed to identify specific contributory dietary components.

BACKGROUND AND AIMS: Extra-intestinal manifestations (EIMs) are a common complication of inflammatory bowel diseases (IBD), affecting up to half of the patients. Despite their high prevalence, information on standardised definitions, diagnostic strategies, and treatment targets is limited. METHODS: As a starting point for a national EIM study network, an interdisciplinary expert panel of 12 gastroenterologists, 4 rheumatologists, 3 ophthalmologists, 6 dermatologists, and 4 patient representatives was assembled. Modified Delphi consensus methodology was used. Fifty-four candidate items were derived from the literature review and expert opinion focusing on five major EIMs (erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis) were rated in three voting rounds. RESULTS: For use in a clinical practice setting and as part of the creation of a prospective registry of patients with EIMs, the panel developed definitions for erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis; identified the appropriate and optimal subspecialists to diagnose and manage each; provided methods to monitor disease course; offered guidance regarding monitoring intervals; and defined resolution and recurrence. CONCLUSIONS: Consensus criteria for appropriate and optimal means of diagnosing and monitoring five EIMs have been developed as a starting point to inform clinical practice and future trial design. Key findings include straightforward diagnostic criteria, guidance regarding who can appropriately and optimally diagnose each, and monitoring options that include patient and physician-reported outcomes. These findings will be used in a national multicenter study network to optimise the management of EIMs.

Extraintestinal manifestations occur frequently in patients with inflammatory bowel disease (IBD) and remain a diagnostic and therapeutic challenge. The aim of the Endpoints for Extraintestinal Manifestations in Inflammatory Bowel Disease Trials (EXTRA) initiative was to achieve international expert consensus on how to assess these manifestations in IBD trials. A systematic literature review was done to identify methods to diagnose extraintestinal manifestations in patients with IBD and measure treatment outcomes. A consensus meeting involving a panel of 41 attendees, including gastroenterologists and referral specialists, was held on March 31, 2021, as part of an International Organization for the Study of Inflammatory Bowel Diseases initiative. The panel agreed that a specialist's expertise is needed to confirm the diagnosis of extraintestinal manifestations before the inclusion of a patient in IBD trials, except for axial spondyloarthritis, for which typical symptoms and MRI can be sufficient. Easy-to-measure endpoints were identified to assess the response of extraintestinal manifestations to treatment without needing specialist involvement. For uveitis, peripheral spondyloarthritis, and arthralgia, endpoint measurements need specialist expertise. The timing of endpoint measurements was discussed for individual extraintestinal manifestations. The EXTRA consensus proposes guidelines on how to thoroughly evaluate extraintestinal manifestations within IBD trials, and recommends that these guidelines are implemented in future trials to enable prospective assessment of these manifestations and comparison between studies.

Background This retrospective study gathered medical/pharmacy claims data on patients with IBD between 01/01/2000 and 03/31/2019 from the IBM® MarketScan® commercial claims database to assess the real-world impact of fatigue on healthcare costs in patients newly diagnosed with inflammatory bowel disease (IBD). Methods Eligible participants were ≥18 years, newly diagnosed with IBD (≥2 separate claims) and had ≥12 months of continuous database enrollment before and after fatigue diagnosis. The date of fatigue diagnosis was the index date; participants were followed for 12 months post-index. Patients with (cases) or without (controls) fatigue were matched 1:1 by propensity score matching. Patients with evidence of prior IBD diagnosis/treatment, or those with a chronic disease other than IBD wherein fatigue is the primary symptom, were excluded. Healthcare resource utilization (HCRU), including hospitalizations, inpatient and outpatient visits, and associated costs was compared between cases and controls. Results Matched IBD cohorts (21,321 cases/21,321 controls) were identified (42% CD and 58% UC) with similar baseline characteristics (average age: 46 years; 60% female). Cases versus controls had significantly more all-cause outpatient visits (incidence rate ratio [IRR], 95% confidence intervals [95% CI]: 1.64 [1.61, 1.67], P Conclusions Presence of fatigue is associated with an increase in HCRU and total medical costs among patients newly diagnosed with IBD.

Total circulating 25-hydroxyvitamin D [25(OH)D)] has been associated with lower risk of colorectal cancer. The physiologic mechanism, however, may be more directly related to the free or bioavailable fraction of 25(OH)D, which is influenced by levels of vitamin D binding protein (VDBP). We assessed the association of prediagnosis total, free, and bioavailable 25(OH)D and VDBP with colorectal cancer risk among predominantly white women in the Nurses' Health Study (NHS) who provided a blood specimen in 1989–1990. We documented 378 cases of colorectal cancer through 2011 and matched them to 689 controls according to age and time of blood draw. We genotyped two common polymorphisms in the gene coding VDBP and calculated free and bioavailable 25(OH)D levels based on total 25(OH)D, VDBP, albumin, and their estimated genotype-specific binding affinities. Total 25(OH)D was associated with lower colorectal cancer risk (P for trend = 0.01). Compared with women in the lowest quintile of total 25(OH)D, those in the highest quintile had a multivariable-adjusted odds ratio (OR) for colorectal cancer of 0.54 [95% confidence interval (CI), 0.33–0.87]. Comparing extreme quintiles, we did not find any significant association with risk of colorectal cancer for VDBP (OR, 0.98; 95% CI, 0.65–1.47), free 25(OH)D (OR, 0.71; 95% CI, 0.46–1.10), or bioavailable 25(OH)D (OR, 0.92; 95% CI, 0.60–1.42). In conclusion, prediagnosis levels of total, but not free or bioavailable 25(OH)D, were associated with lower colorectal cancer risk. Although our findings support an inverse association of vitamin D with colorectal cancer, this association does not appear to be due to the unbound or bioavailable fraction of circulating vitamin D. Cancer Prev Res; 9(8); 664–72. ©2016 AACR.

The Supplementary Methods include further details on "Assessment of dietary and lifestyle factors" and "Statistical analyses". Supplementary Table 1 shows subsite-specific risk of colorectal cancer according to vitamin D-related biomarkers in the Nurses' Health Study (1990-2011). Supplementary Table 2 shows the stratified analysis of the association of plasma total 25(OH)D and VDBP with risk of colorectal cancer in the Nurses' Health Study (1990-2011).

For decades, variability in clinical efficacy of the widely used inflammatory bowel disease (IBD) drug 5-aminosalicylic acid (5-ASA) has been attributed, in part, to its acetylation and inactivation by gut microbes. Identification of the responsible microbes and enzyme(s), however, has proved elusive. To uncover the source of this metabolism, we developed a multi-omics workflow combining gut microbiome metagenomics, metatranscriptomics and metabolomics from the longitudinal IBDMDB cohort of 132 controls and patients with IBD. This associated 12 previously uncharacterized microbial acetyltransferases with 5-ASA inactivation, belonging to two protein superfamilies: thiolases and acyl-CoA N-acyltransferases. In vitro characterization of representatives from both families confirmed the ability of these enzymes to acetylate 5-ASA. A cross-sectional analysis within the discovery cohort and subsequent prospective validation within the independent SPARC IBD cohort (n = 208) found three of these microbial thiolases and one acyl-CoA N-acyltransferase to be epidemiologically associated with an increased risk of treatment failure among 5-ASA users. Together, these data address a longstanding challenge in IBD management, outline a method for the discovery of previously uncharacterized gut microbial activities and advance the possibility of microbiome-based personalized medicine.

Purpose of Review: Crohn’s Disease (CD) is a chronic inflammatory disease that can lead to progressive damage to the gastrointestinal tract and significant disability. Early, “top-down” biologic therapy is recommended in moderate-to-severe CD to induce remission and to prevent hospitalization and complications. However, an estimated 20–30% of patients with CD have a mild disease course and may not garner sufficient benefit from expensive, immunosuppressing agents to justify their risks. Herein, we review characteristics of patients with mild CD, the available options for disease treatment and monitoring, and future directions of research. Recent Findings: For ambulatory outpatients with low-risk, mild, ileal or ileocolonic CD, induction of remission with budesonide is recommended. For colonic CD, sulfasalazine is a reasonable choice, although other aminosalicylates have no role in the treatment of CD. No large, randomized trial has supported the use of antibiotics or antimycobacterials in the treatment of CD. Partial Enteral Nutrition and Crohn’s Disease Exclusion Diets may be appropriate for inducing remission in some adult patients, with trials ongoing. Select patients with mild-to-moderate CD may benefit from maintenance therapy with azathioprines or gut specific biologics, such as vedolizumab. The role of complementary and alternative medicine is not well defined. Summary: The identification, risk stratification, and monitoring of patients with mild CD can be a challenging clinical scenario. Some patients with low risk of disease progression may be appropriate for initial induction of remission with budesonide or sulfasalazine, followed by close clinical monitoring. Future research should focus on pre-clinical biomarkers to stratify disease, novel therapies with minimal systemic immune suppression, and validation of rigorous clinical monitoring algorithms.

Background Up to one-third of patients hospitalized for acute severe colitis secondary to inflammatory bowel diseases (IBD) do not adequately respond to intravenous steroids. There is an unmet need to identify a useful predictor for rescue treatment in this cohort of patients. Aims The aim of this study was to assess the predictive efficacy of fecal calprotectin in identifying the need for medical or surgical therapy in patients with acute severe colitis. Methods We conducted a multicenter retrospective cohort study including patients with ulcerative colitis (UC) who were hospitalized for severe exacerbation of colitis. The primary outcome was the need for in-hospital medical or surgical rescue therapy. Univariate and multivariate logistic regression was performed to identify predictors of rescue therapy. Results Our study included 147 patients with UC. One-third (33%) required rescue therapy, and 13% underwent colectomy. Patients requiring rescue therapy had significantly higher fecal calprotectin (mean 1748 mcg/g vs 1353 mcg/g, P = .02) compared with those who did not. A fecal calprotectin >800 mcg/g independently predicted the need for inpatient medical rescue therapy (odds ratio, 2.61; 95% CI, 1.12-6.12). An admission calprotectin >800 mcg/g independently predicted surgery within 3 months (odds ratio, 2.88; 95% CI, 1.01-8.17). Conclusions Fecal calprotectin levels may serve as a useful noninvasive predictor of medical and surgical risk in individuals with UC presenting with acute severe colitis. This approach can facilitate earlier therapeutic interventions and improve outcomes.

Background & Aims 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. Methods 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. Results 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. Conclusions Neither Vedolizumab nor TNF-antagonists were associated with increased risk of new or recurrent cancers in patients with prior malignancy.

Plasma cells (PCs) constitute a significant fraction of colonic mucosal cells and contribute to inflammatory infiltrates in ulcerative colitis (UC). While gut PCs secrete bacteria-targeting IgA antibodies, their role in UC pathogenesis is unknown. We performed single-cell V(D)J- and RNA-seq on sorted B cells from the colon of healthy individuals and patients with UC. A large fraction of B cell clones is shared between different colon regions, but inflammation in UC broadly disrupts this landscape, causing transcriptomic changes characterized by an increase in the unfolded protein response (UPR) and antigen presentation genes, clonal expansion, and isotype skewing from IgA1 and IgA2 to IgG1. We also directly expressed and assessed the specificity of 152 mAbs from expanded PC clones. These mAbs show low polyreactivity and autoreactivity and instead target both shared bacterial antigens and specific bacterial strains. Altogether, our results characterize the microbiome-specific colon PC response and how its disruption might contribute to inflammation in UC.

Women with inflammatory bowel disease (IBD) face difficult decisions regarding treatment during pregnancy: while the majority of IBD medications are safe, there is substantial societal pressure to avoid exposures during pregnancy. However, discontinuation of IBD medications risks a disease flare occurring during pregnancy. This study quantified women’s knowledge about pregnancy and IBD and their willingness to accept the risks of adverse pregnancy outcomes to avoid disease activity or medication use during pregnancy. Women with IBD recruited from four centers completed an online discrete-choice experiment stated-preference study including eight choice tasks and the Crohn’s and Colitis Pregnancy Knowledge questionnaire. Random-parameters logit was used to estimate preferences for both the respondent personally and what the respondent thought most women would prefer. We also tested for systematically different preferences among individuals with different demographic and personal characteristics, including IBD knowledge. The primary outcome was the maximum acceptable risk of premature birth, birth defects, or miscarriage that women with IBD were willing to accept to avoid (1) taking an IBD medication or (2) having a disease flare during pregnancy. Among 230 respondents, women would accept, on average, up to a 4.9% chance of miscarriage to avoid a disease flare. On average, there were no statistically significant differences in women’s preferences for continuing versus avoiding medication in the absence of a flare. However, prior understanding of IBD and pregnancy significantly affected preferences for IBD medication use during pregnancy: women with “poor knowledge” would accept up to a 6.4% chance of miscarriage to avoid IBD medication use during pregnancy, whereas women with “adequate knowledge” would accept up to a 5.1% chance of miscarriage in order to remain on their medication. Respondents’ personal treatment preferences did not differ from their assessment of other women’s preferences. Women with IBD demonstrated a strong preference for avoiding disease activity during pregnancy. Knowledge regarding pregnancy and IBD was a strong modifier of preferences for continuation of IBD medications during pregnancy. These findings point to an important opportunity for intervention to improve disease control through education to increase medication adherence and alleviate unnecessary fears about IBD medication use during pregnancy.

Background Fatigue is a disabling symptom in patients with inflammatory bowel disease (IBD). Its prevalence, mechanism, and impact remain poorly understood. We determined changes in fatigue status over time and identified predictors of incident or resolving fatigue. Methods This was a prospective study nested within the IBD Partners cohort. Participants prospectively completed the Multidimensional Fatigue Inventory and the Functional Assessment of Chronic Illness Therapy-Fatigue at baseline, 6 months, and 12 months. A Functional Assessment of Chronic Illness Therapy-Fatigue score ≤43 defined significant fatigue. Multivariable regression models using baseline covariates were used to identify risk factors for incident fatigue at 6 months and to predict the resolution of fatigue. Results A total of 2429 patients (1605 with Crohn disease, 824 with ulcerative colitis) completed a baseline assessment, and 1057 completed a second assessment at 6 months. Persistent fatigue (at baseline and at 6 months) was the most common pattern, affecting two-thirds (65.8%) of patients. One-sixth (15.7%) of patients had fatigue at 1 timepoint, whereas fewer than one-fifth (18.5%) of patients never reported fatigue. Among patients not fatigued at baseline, 26% developed fatigue at 6 months. The strongest predictor of incident fatigue was sleep disturbance at baseline (odds ratio, 2.91; 95% confidence interval, 1.48–5.72). In contrast, only 12.3% of those with fatigue at baseline had symptom resolution by month 6. Resolution was more likely in patients with a diagnosis of ulcerative colitis, quiescent disease, and an absence of significant psychological comorbidity. Conclusions Fatigue is common in patients with IBD. However, only a few fatigued patients experience symptom resolution at 6 or 12 months, suggesting the need for novel interventions to ameliorate its impact.

Background: Therapeutic drug monitoring (TDM) is important in optimizing use of biologics in inflammatory bowel diseases (IBD). However, the role of proactive TDM during remission remains uncertain. Methods: This retrospective study included patients receiving infliximab (IFX) therapy at Massachusetts General Hospital or Erasmus University Medical Center. All eligible patients had completed induction phase of IFX and were in clinical and endoscopic remission. Our primary outcome was clinical relapse within 2 years after baseline. Multivariable regression models examined the association between infliximab trough levels during remission and relapse, need for IBD-related surgery or hospitalization. Results: Our study cohort included 110 patients with IBD (72 CD, 38 UC) on IFX maintenance therapy. In total, 12 patients (10.9%) experienced relapse of disease over 2 years. The mean IFX trough level at baseline was 8.0 µg/mL (± 8.6) and did not differ between the institutions. 49.1% of patients had levels < 5 µg/mL and 2.7% had antibodies to infliximab at baseline. There was no difference in the mean IFX trough levels between patients who relapsed (7.5 µg/mL ± 3.7 µg/mL) over 24 months compared to those who did not (8.1 µg/mL ± 7.9 µg/mL, p = 0.815). On multivariable logistic regression analysis, IFX trough levels at baseline were not associated with relapse of disease over 24 months (OR 1.01, 95% CI 0.93–1.09, p = 0.856). Conclusion: This retrospective multicenter study provides evidence that IFX trough levels during quiescent disease do not predict relapse over 2 years, suggestive that proactive TDM in this setting is not warranted.

Aim: We conducted this network meta-analysis to compare the efficacy and safety of targeted pharmacotherapies and fecal microbial transplantation (FMT). Patients & methods: Nineteen studies were included and there was only one head-to-head randomized controlled trial (adalimumab vs vedolizumab). Results: All interventions, including FMT, were superior to a placebo in inducing clinical remission (except adalimumab – odds ratio 1.66; 95% CI: 0.97–2.85), clinical response and endoscopic remission. FMT was comparable with other agents in achieving all efficacy outcomes. Infliximab was ranked highest in inducing clinical remission (surface under the cumulative ranking, 0.8). There was no difference in safety outcomes between FMT and other targeted therapies. Conclusion: FMT is as efficacious and as safe as other targeted therapies in inducing clinical remission, clinical response and endoscopic remission. Further studies to assess the long-term benefits are needed in order to reach a definitive conclusion.

Background No dietary factors have yet been shown to conclusively impact the incidence of microscopic colitis (MC). Here, we sought to examine the relationship between alcohol intake and the risk of MC. Methods We conducted a prospective cohort study of 209,902 participants (age range, 28.5–66.7 years) enrolled in the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII). Validated data on alcohol consumption were collected at baseline in 1986 in the NHS and 1991 in the NHSII and updated every 4 years. Diagnoses of MC were confirmed via review of histopathology data. We used Cox proportional hazards modeling to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Results Through 2016 in the NHS and 2017 in the NHSII, we confirmed 352 incident cases of MC over 4,994,324 person-years. Higher alcohol consumption was associated with an increased risk of MC (Ptrend < .001). Compared to non-users, the aHRs of MC were 1.20 (95% CI, 0.86–1.67) for consumers of 0.1–4.9 g/day of alcohol, 1.90 (95% CI, 1.34–2.71) for consumers of 5–14.9 g/day, and 2.31 (95% CI, 1.54–3.46) for consumers of ≥15 g/day. The associations were consistent across the histologic subtypes of collagenous and lymphocytic colitis (Pheterogeneity = .523). When stratified by alcohol type, the risk according to every 2 servings/week appeared to be strongest with consumption of wine (aHR, 1.08; 95% CI, 1.04–1.12) as compared to beer (aHR, 1.01; 95% CI, 0.91–1.12) or liquor (aHR, 1.00; 95% CI, 0.92–1.09). Conclusions Alcohol consumption was associated with an increased risk of MC. Further studies are needed to determine the mechanism underlying these associations, as well as the impact of reducing alcohol intake in patients with MC.

Inflammatory bowel diseases, principally Crohn's disease and ulcerative colitis, are multifactorial chronic conditions. Alterations in gut microbial patterns partly affect disease onset and severity. Moreover, the evolution of dietary patterns, and their effect on gut microbial behaviour, have been shown to play a crucial role in disease processes. This Viewpoint reviews the role of dietary patterns, their influence on the structure and function of the gut microbiome, and their effects on inflammation and immunity in individuals with inflammatory bowel disease. We also discuss innovative dietary intervention strategies, summarise findings that have been used to develop recommendations for clinical practice, and provide suggestions for the design of future studies for development of precision nutrition in patients with inflammatory bowel disease.

Introduction: Data about the safety of vedolizumab and ustekinumab are lacking in older patients with inflammatory bowel disease. The objective was to compare the safety of vedolizumab and ustekinumab therapies in older patients (>60 years) with inflammatory bowel disease. Methods: This retrospective study included patients with Crohn’s disease or ulcerative colitis initiating vedolizumab, ustekinumab or anti-TNF therapy at >60 years of age. We examined the occurrence of adverse events within one year after therapy. Results: This study included 182 patients: 53 were treated with vedolizumab (22 patients with Crohn’s disease and 31 with ulcerative colitis), 31 with ustekinumab (30 Crohn’s disease and one ulcerative colitis) and 98 with anti-TNF (63 Crohn’s disease and 35 ulcerative colitis). At one year, there was no difference in terms of safety in patients with Crohn’s disease between vedolizumab and ustekinumab considering the number of adverse events per year of follow-up (p = 0.258). For ulcerative colitis and Crohn’s disease, the occurrence of adverse events per year of follow-up was similar between vedolizumab and anti-TNF (p = 0.274 and p = 0.876, respectively). Conclusions: Safety was similar between vedolizumab and ustekinumab in older patients with inflammatory bowel disease.

While fecal calprotectin (FC) is used to assess disease activity in ulcerative colitis (UC) there are little data concerning the role of serial FC levels at diagnosis in predicting clinical course. We sought to determine whether FC at diagnosis or early change following therapy predicts clinical outcomes in pediatric UC.Methods: Children with newly diagnosed UC were treated with standardized regimens of mesalamine or corticosteroids (CS). CS tapering and escalation to additional therapy or colectomy were by protocol. Patients with baseline or week 4 or week 12 FC levels were included in the analysis. Our primary outcome was CS-free remission on mesalamine at week 52. We compared the prognostic value of a baseline FC as well as a change in FC by week 4 or week 12 in predicting clinical outcomes.The study included 352 children (113 initial mesalamine, 239 initial CS, mean age 12.6 years) with UC. At Week 52, 135 (38.3%), 84 (23.8%), and 19 (5.4%) children achieved CS-free remission, needed anti-tumor necrosis factor therapy or had colectomy respectively. Baseline FC was not associated with CS-free remission at week 52. However, both week 4 (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.901.00) and week 12 FC levels (OR 0.91, 95% CI 0.87-0.96) were associated with outcomes, with the latter having a stronger association with CS-free remission. Patients with a75% decrease by 12 weeks, had a 3-fold increased likelihood of CS-free remission at 1 year.Longitudinal changes in FC may predict 1 year outcomes better than values at diagnosis in children with a new diagnosis of UC.

While the role of anti-drug antibodies in mediating loss of response to infliximab (IFX) is known, it is possible that there are different clinical implications for high compared to low titers of antibodies to infliximab (ATI). The impact of ATI titer on efficacy of subsequent anti-TNF treatment has not been established previously. This is a multicenter retrospective cohort study of individuals with IBD who discontinued infliximab due to development of ATI and were subsequently switched to adalimumab therapy. IFX anti-drug antibody titer level was measured using Mayo or Esoterix assays. We examined clinical and endoscopic response to adalimumab at 3 months, 12 months, and 2 years. Our study included 90 patients (69 CD, 17 UC, 4 CD of the ileoanal pouch) with IBD. The median antibody titer levels for the Esoterix (208 u/mL) or Mayo clinic laboratory (236 u/mL) were similar (p > 0. 50). Patients with high ATI titers (median 824 u/ml, IQR 405–1250 u/ml) were as likely to respond to adalimumab as those with low titers (median 76u/ml, IQR 41–129 u/ml). At 3 months and 12 months, the rates of clinical response/remission to adalimumab therapy were 78% and 77%, respectively, among those with high ATI titers and 81% and 84% among those with low ATI titers (p = 0.81 and 0.62, respectively). In patients who initiated a different therapeutic mechanism after adalimumab, the response rates were similar to that observed with adalimumab. The presence of high titers of anti-drug antibodies to IFX is not predictive of treatment failure with adalimumab.