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Background Individuals with inflammatory bowel disease (IBD) have elevated symptoms of anxiety and depression. The burden of such symptoms, accompanied by functional impairment in IBD, is not well documented, nor is utilization of mental health care in this population. Methods Adults ≥18 years were identified in the cross-sectional 2015–2016 National Health Interview Survey. Responses from the Kessler Index were used to estimate the national prevalence of psychological distress with impairment and mental health-care use in IBD. Factors associated with psychological distress with impairment in IBD were analyzed using logistic regression. Results The prevalence of psychological distress with impairment was significantly higher in IBD than non-IBD adults (7.69% vs. 3.50%, respectively; P Conclusions A significant number of adults with IBD in the United States have psychological distress accompanied by functional impairment. However, mental health care is underutilized in this population. Many of these individuals find the cost of mental health care unaffordable, struggle to find a health provider, and experience repeated emergency room visits. Ongoing efforts to improve mental health care in IBD should address issues of access and cost. Additionally, these efforts should seek to understand other barriers to mental health-care use.

Background: Patients with ulcerative colitis (UC) often report impaired health-related quality of life (HRQoL). Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of UC. In addition to previous demonstrations of improved clinical measures (e.g., Mayo score), tofacitinib has been shown to improve HRQoL in patients with UC. This analysis explored the interrelationships among tofacitinib treatment, HRQoL, and disease activity (measured using Mayo subscores) using mediation modeling. Methods: Data were collected from two 8-week induction studies (OCTAVE Induction 1 and 2) in patients with moderate to severe UC treated with tofacitinib or placebo. Two mediation models were specified. First, Mayo subscores were mediators between the binary treatment variable (tofacitinib vs placebo) and the eight Short Form-36 Health Survey (SF 36) domain scores as outcomes. Second, the four Inflammatory Bowel Disease Questionnaire (IBDQ) domain scores served as outcomes. Both models used data collected at Week 8. Results: Overall, 1073 and 1079 patients were included in the SF-36- and IBDQ-based models, respectively. For all SF-36 domains, improvements in Mayo subscores were estimated to explain 65.6% (bodily pain) to 92.9% (mental health) of the total treatment effect on SF-36 domain scores (all p

We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD).This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation.A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients.UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

Longstanding and extensive ulcerative colitis (UC) are associated with the subsequent development of colorectal cancer (CRC). This article summarizes key strategies for colonoscopic surveillance, the most widely used and evidence-based method of CRC prevention. As currently constituted and practiced, surveillance examinations every 1 to 3 years with lesion detection and removal using high-definition endoscopic systems with or without pancolonic spray-dye chromoendoscopy is the best method for mitigating the development of CRC morbidity and mortality. For patients with primary sclerosing cholangitis with UC, surveillance should begin at the time of diagnosis and colonoscopy should be performed annually.

Background:Inflammatory bowel disease (IBD) is not associated with worse coronavirus disease 2019 (COVID-19) outcomes. However, data are lacking regarding the long-term impact of severe acute respiratory syndrome coronavirus 2 infection on the disease course of IBD.Objectives:We aimed to investigate the effect of COVID-19 on long-term outcomes of IBD.Design:We performed a multicenter case–control study of patients with IBD and COVID-19 between February 2020 and December 2020.Methods:Cases and controls were individuals with IBD with presence or absence, respectively, of COVID-19-related symptoms and confirmatory testing. The primary composite outcome was IBD-related hospitalization or surgery.Results:We identified 251 cases [ulcerative colitis ( n = 111, 45%), Crohn’s disease ( n = 139, 55%)] and 251 controls, with a median follow-up of 394 days. The primary composite outcome of IBD-related hospitalization or surgery occurred in 29 (12%) cases versus 38 (15%) controls ( p = 0.24) and on multivariate Cox regression, COVID-19 was not associated with increased risk of adverse IBD outcomes [adjusted hazard ratio (aHR): 0.84, 95% confidence interval [CI]: 0.44–1.42]. When stratified by infection severity, severe COVID-19 was associated with a numerically increased risk of adverse IBD outcomes (aHR: 2.43, 95% CI: 1.00–5.86), whereas mild-to-moderate COVID-19 was not (aHR: 0.68, 95% CI: 0.38–1.23).Conclusion:In this case–control study, COVID-19 did not have a long-term impact on the disease course of IBD. However, severe COVID-19 was numerically associated with worse IBD outcomes, underscoring the continued importance of risk mitigation and prevention strategies for patients with IBD during the ongoing COVID-19 pandemic.

Background & Aims Little is known about the effects of discontinuing mesalamine therapy for patients with Crohn’s disease (CD) who initiate therapy with an anti–tumor necrosis factor (anti-TNF) agent. We analyzed data from 2 national population cohorts to compare outcomes of patients with CD already on mesalamine therapy who started treatment with an anti-TNF agent and then either stopped or continued mesalamine. Methods The primary outcome was any adverse clinical event, defined as a composite of new corticosteroid use or CD-related hospitalization or surgery. We collected data from the Truven MarketScan (IBM, Armonk, NY) health claims database in the United States and the Danish health registers. Our analysis included patients with CD who started anti-TNF therapy after at least 90 days of oral mesalamine therapy. Patients were classified as stopping mesalamine if therapy was discontinued within 90 days of starting anti-TNF. We performed multivariable Cox regression models controlling for demographics, clinical factors, and health care utilization. Adjusted hazard ratios with 95% CIs were calculated, comparing stopping mesalamine with continuing mesalamine. Results A total of 3178 patients with CD were included in our final analysis (2960 in the United States and 218 in Denmark). Stopping mesalamine after initiating anti-TNF therapy was not associated with an increased risk of adverse clinical events in the US cohort (adjusted hazard ratio, 0.89; 95% CI, 0.77–1.03; P = .13) or in the Danish cohort (adjusted hazard ratio, 1.13; 95% CI, 0.68–1.87; P = .63). Similar results were obtained from sensitivity analyses of concomitant immunomodulator use and duration of mesalamine treatment before initiation of anti-TNF therapy. Conclusions In a retrospective analysis of 2 national databases, we found that stopping mesalamine therapy for patients with CD who were starting anti-TNF therapy did not increase their risk of adverse clinical events. These results should be validated in a prospective study.

Background & aims Therapeutic drug monitoring (TDM) is widely available for biologic therapies in patients with inflammatory bowel disease (IBD). We reviewed current data and provided expert opinion regarding the clinical utility of TDM for biologic therapies in IBD. Methods We used a modified Delphi method to establish consensus. A comprehensive literature review was performed regarding the use of TDM of biologic therapy in IBD and presented to international IBD specialists. Subsequently, 28 statements on the application of TDM in clinical practice were rated on a scale of 1 to 10 (1 = strongly disagree and 10 = strongly agree) by each of the panellists. Statements were accepted if 80% or more of the participants agreed with a score ≥7. The remaining statements were discussed and revised based on the available evidence followed by a second round of voting. Results The panel agreed on 24 (86%) statements. For anti-tumor necrosis factor (anti-TNF) therapies, proactive TDM was found to be appropriate after induction and at least once during maintenance therapy, but this was not the case for the other biologics. Reactive TDM was appropriate for all agents both for primary non-response and secondary loss of response. The panellists also agreed on several statements regarding TDM and appropriate drug and anti-drug antibody (ADA) concentration thresholds for biologics in specific clinical scenarios. Conclusion Consensus was achieved towards the utility of TDM of biologics in IBD, particularly anti-TNF therapies. More data are needed especially on non-anti-TNF biologics to further define optimal drug concentration and ADA thresholds as these can vary depending on the therapeutic outcomes assessed.

Background Crohn's disease (CD) has the highest prevalence among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Caucasian populations (NJ). We evaluated a set of well-established CD-susceptibility variants to determine if they can explain the increased CD risk in the AJ population. Methods We recruited 369 AJ CD patients and 503 AJ controls, genotyped 22 single nucleotide polymorphisms (SNPs) at or near 10 CD-associated genes, NOD2, IL23R, IRGM, ATG16L1, PTGER4, NKX2-3, IL12B, PTPN2, TNFSF15 and STAT3, and assessed their association with CD status. We generated genetic scores based on the risk allele count alone and the risk allele count weighed by the effect size, and evaluated their predictive value. Results Three NOD2 SNPs, two IL23R SNPs, and one SNP each at IRGM and PTGER4 were independently associated with CD risk. Carriage of 7 or more copies of these risk alleles or the weighted genetic risk score of 7 or greater correctly classified 92% (allelic count score) and 83% (weighted score) of the controls; however, only 29% and 47% of the cases were identified as having the disease, respectively. This cutoff was associated with a >4-fold increased disease risk (p < 10e-16). Conclusions CD-associated genetic risks were similar to those reported in NJ population and are unlikely to explain the excess prevalence of the disease in AJ individuals. These results support the existence of novel, yet unidentified, genetic variants unique to this population. Understanding of ethnic and racial differences in disease susceptibility may help unravel the pathogenesis of CD leading to new personalized diagnostic and therapeutic approaches.

N-glycosylation status of purified beta-haptoglobin from sera of 17 patients, and from sera of 14 healthy volunteer subjects, was compared by blotting with various lectins and antibodies. Patients in this study were diagnosed as having colon cancer through histological examination of each tumor tissue by biopsy. Blotting index of serum beta-haptoglobin with Aleuria aurantia lectin (AAL) was clearly higher for cancer patients than for healthy subjects. No such distinction was observed for blotting with three other lectins and two monoclonal antibodies. To determine tumor-associated reactivity of AAL binding as compared to inflammatory processes in colonic tissues, beta-haptoglobin separated from sera of 5 patients with Crohn's disease (CD), and 4 patients with ulcerative colitis (UC), was studied. All these cases, except one case of UC, showed AAL index lower than that in cancer cases, similarly to healthy subjects. The higher AAL binding of beta-haptoglobin in colon cancer patients than in healthy subjects appeared to be due to alpha-L-fucosyl residue, since it was eliminated by bovine kidney alpha-fucosidase treatment. N-linked glycans of serum haptoglobin from colon cancer patients vs. healthy subjects were released by N-glycanase, fluorescence-labeled, and subjected to normal-phase high performance liquid chromatography (NP-HPLC). Glycan structures were determined based on glucose unit (GU) values and their changes upon sequential treatment with various exoglycosidases. Glycosyl sequences and their branching status of glycans from 14 cases of serum beta-haptoglobin were characterized. The identified glycans were sialylated or nonsialylated, bi-antennary or tri-antennary structures, with or without terminal fucosylation.

Studies have shown that rectal sparing and patchiness develop in treated and longstanding ulcerative colitis (UC), making the distinction from Crohn colitis increasingly difficult after treatment is initiated. However, no histologic studies of the incidence of rectal sparing in adults at UC onset have been performed. Colectomy specimens from 46 patients with classic UC histologic features and no Crohn disease features were identified. Biopsy specimens obtained before medical therapy were retrieved and examined blindly by 2 pathologists, along with appropriate control samples. Slides were scored for chronicity (crypt branching, subcryptal plasma cells, lamina propria plasma cells) and activity (cryptitis, crypt abscesses, epithelial injury). In 28 cases, only rectal biopsy specimens were taken; for 16, rectal and at least 1 proximal biopsy specimen were taken. All cases showed rectal involvement; none had rectal sparing at initial biopsy. Of 16 cases with rectal and more proximal biopsy specimens, 5 (31%) showed relative rectal sparing (lower scores in rectum than in more proximal sites). In 16 cases with rectal and more proximal biopsy specimens, chronicity and activity scores were higher in the rectum than in more proximal sites (P = .01; chronicity and activity). The mean overall chronicity score decreased in a linear manner from rectum to cecum. The rectum is involved and shows evidence of chronicity and activity at disease onset in UC, using colectomy as the gold standard for diagnosis. Because rectal sparing at UC onset has been reported, a prospective study using uniform biopsy protocols is needed to establish the true incidence of rectal sparing at presentation.