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Epidemiological and experimental studies have suggested that diet is one of the environmental factors that contributes to the onset and pathophysiology of ulcerative colitis. Although many patients suffering from ulcerative colitis attribute their symptoms or disease relapse to dietary factors, only a few well-designed randomized controlled trials have been done to investigate the role of diet in the management of ulcerative colitis. Here, we review the potential mechanisms of the relationship between diet and pathogenesis of ulcerative colitis and summarize randomized controlled dietary interventions that have been conducted in ulcerative colitis patients.

Tulisokibart is a tumor necrosis factor-like cytokine 1A (TL1A) monoclonal antibody in development for the treatment of moderately to severely active ulcerative colitis. A genetic-based diagnostic test was designed to identify patients with an increased likelihood of response. We randomly assigned patients with glucocorticoid dependence or failure of conventional or advanced therapies for ulcerative colitis to receive intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10) or placebo. Cohort 1 included patients regardless of status with respect to the test for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response. The primary analysis was performed in cohort 1; the primary end point was clinical remission at week 12. Patients with a positive test for likelihood of response from cohorts 1 and 2 were combined in prespecified analyses. In cohort 1, a total of 135 patients underwent randomization. A significantly higher percentage of patients who received tulisokibart had clinical remission than those who received placebo (26% vs. 1%; difference, 25 percentage points; 95% confidence interval [CI], 14 to 37; P<0.001). In cohort 2, a total of 43 patients underwent randomization. A total of 75 patients with a positive test for likelihood of response underwent randomization across both cohorts. Among patients with a positive test for likelihood of response (cohorts 1 and 2 combined), clinical remission occurred in a higher percentage of patients who received tulisokibart than in those who received placebo (32% vs. 11%; difference, 21 percentage points; 95% CI, 2 to 38; P = 0.02). Among all the enrolled patients, the incidence of adverse events was similar in the tulisokibart and placebo groups; most adverse events were mild to moderate in severity. In this short-term trial, tulisokibart was more effective than placebo in inducing clinical remission in patients with moderately to severely active ulcerative colitis. (Funded by Prometheus Biosciences, a subsidiary of Merck; ARTEMIS-UC ClinicalTrials.gov number, NCT04996797.).

There is an unmet need for novel blood-based biomarkers that offer timely and accurate diagnostic and prognostic testing in inflammatory bowel diseases (IBD). We aimed to investigate the diagnostic and prognostic utility of serum calprotectin (SC) in IBD. A total of 171 patients (n=96 IBD, n=75 non-IBD) were prospectively recruited. A multi-biomarker model was derived using multivariable logistic regression analysis. Cox proportional hazards model was derived to assess the contribution of each variable to disease outcomes. SC correlated strongly with current biomarkers, including fecal calprotectin (FC) (n=50, ρ=0.50, P=1.6 × 10 ). SC was the strongest individual predictor of IBD diagnosis (odds ratio (OR): 9.37 (95% confidence interval (CI): 2.82-34.68), P=4.00 × 10 ) compared with other markers (C-reactive protein (CRP): OR 8.52 (95% CI: 2.75-28.63), P=2.80 × 10 ); albumin: OR 6.12 (95% CI: 1.82-22.16), P=0.004). In a subset of 50 patients with paired SC and FC, the area under receiver operating characteristic discriminating IBD from controls was better for FC than for SC (0.99, (95% CI 0.87-1.00) and 0.87 (95% CI:0.78-0.97), respectively; P=0.01). At follow-up (median 342 days; interquartile range: 88-563), SC predicted treatment escalation and/or surgery in IBD (hazard ratio (HR) 2.7, 95% CI: 1.1-4.9), in particular Crohn's disease (CD) (HR 4.2, 95% CI 1.2-15.3). A model incorporating SC and either CRP or albumin has a positive likelihood ratio of 24.14 for IBD. At 1 year, our prognostic model can predict treatment escalation in IBD in 65% of cases (95% CI: 43-79%) and 80% (95% CI: 31-94%) in CD if ≥2 blood marker criteria are met. A diagnostic and prognostic model that combines SC and other blood-based biomarkers accurately predicts the inflammatory burden in IBD and has the potential to predict disease and its outcomes. Our data warrant further detailed exploration and validation in large multicenter cohorts.

Background Filgotinib is an oral, once‐daily, Janus kinase 1 preferential inhibitor approved for treatment of ulcerative colitis (UC) following the phase 2b/3 SELECTION trial. Identification of patient populations and factors associated with long‐term treatment response trajectories may improve UC management. Objective We aimed to identify and describe distinct patient subgroups of response to filgotinib based on partial Mayo Clinic Score (pMCS) trajectories over time. Methods In these post hoc analyses of SELECTION, group‐based trajectory modeling (GBTM) was applied to pMCS to describe groups of distinct, symptom‐based patient trajectories using data from patients who responded to filgotinib 200 or 100 mg and continued receiving filgotinib up to week 58. Patient demographics, disease characteristics, and week 10 response were compared between the groups. Achievement of a patient‐level multi‐component endpoint of comprehensive disease control (CDC) was assessed in each group. Results GBTM identified five distinct patient populations with different response trajectories; 67.5% of patients had beneficial trajectories. The beneficial trajectory groups generally had higher proportions of patients who were recently diagnosed (<1 year), were receiving filgotinib 200 mg and were biologic‐naive versus the relapsing trajectory groups (4%–9% vs. 4%–5%; 43%–65% vs. 36%–46%; 54%–70% vs. 35%–58%, respectively). Furthermore, 55.4% of patients had sustained beneficial trajectories, with low baseline endoscopic subscores (≥43% of patients had a subscore of 2) and strong week 10 FCP responses (≥61% of patients with >50% decrease in FCP from baseline). Sustained beneficial trajectory groups had a higher probability of achieving CDC at week 58 than other groups (31%–32% vs. 0%–7%). Conclusions Beneficial long‐term response trajectories and achievement of CDC with filgotinib were associated with being biologic‐naive and having less severe disease at baseline. Early estimation of sustained and CDC may facilitate patient identification and development of personalized management strategies in UC. ClinicalTrials.gov Identifier NCT02914522.

BackgroundIndirect treatment comparisons using patient-level data are increasing in popularity within inflammatory bowel disease research. We compared the efficacy of adalimumab and vedolizumab for biologic-naïve moderate–severe ulcerative colitis (UC) using indirect comparisons of phase 3 clinical trials and compared the results to the RCT VARSITY.DesignPooled analysis of patient-level data from 518 biologic-naïve patients with UC was performed using GEMINI-1 and ULTRA-1. Proportions of patients achieving week 6 clinical remission and clinical response were compared, and propensity score matching and multivariate logistic regression were used to account for potential confounders. These results were compared to those derived from VARSITY.ResultsA numerically greater proportion of vedolizumab-treated patients from GEMINI-1 achieved week 6 clinical remission compared to those treated with adalimumab [136/388 (35.1%) vs. 38/130 (29.2%)]. Similar findings were observed among the propensity score matched cohort [33/110 (30.0%) vs. 25/110 (22.7%), adjusted OR (aOR) 1.56 (95% confidence interval (CI) 0.81–3.02), p = 0.187]. A similar magnitude for absolute difference in the proportions of patients achieving week 6 clinical remission was observed from VARSITY in vedolizumab compared to adalimumab [131/305 (43.0%) vs. 114/307 (37.1%), OR 1.27 (95% CI 0.92–1.76), p = 0.142].ConclusionsIn this post hoc analysis, a similar magnitude in the absolute difference of efficacy at week 6 among biologic-naïve patients was observed using indirect comparisons of phase 3 clinical trial data as was observed in VARSITY. Indirect comparisons using patient-level clinical trial data could be used to inform drug choices for future head-to-head trials and guide positioning of drugs in the absence of head-to-head trials.

Previous studies identifying patients with inflammatory bowel disease using administrative codes have yielded inconsistent results. Our objective was to develop a robust electronic medical record-based model for classification of inflammatory bowel disease leveraging the combination of codified data and information from clinical text notes using natural language processing. Using the electronic medical records of 2 large academic centers, we created data marts for Crohn's disease (CD) and ulcerative colitis (UC) comprising patients with ≥1 International Classification of Diseases, 9th edition, code for each disease. We used codified (i.e., International Classification of Diseases, 9th edition codes, electronic prescriptions) and narrative data from clinical notes to develop our classification model. Model development and validation was performed in a training set of 600 randomly selected patients for each disease with medical record review as the gold standard. Logistic regression with the adaptive LASSO penalty was used to select informative variables. We confirmed 399 CD cases (67%) in the CD training set and 378 UC cases (63%) in the UC training set. For both, a combined model including narrative and codified data had better accuracy (area under the curve for CD 0.95; UC 0.94) than models using only disease International Classification of Diseases, 9th edition codes (area under the curve 0.89 for CD; 0.86 for UC). Addition of natural language processing narrative terms to our final model resulted in classification of 6% to 12% more subjects with the same accuracy. Inclusion of narrative concepts identified using natural language processing improves the accuracy of electronic medical records case definition for CD and UC while simultaneously identifying more subjects compared with models using codified data alone.

BACKGROUNDHyperbaric oxygen therapy (HBOT) markedly increases tissue oxygen delivery. Case series suggest it may have a potential therapeutic benefit in ulcerative colitis (UC). We investigated the therapeutic potential of HBOT as an adjunct to steroids for UC flares requiring hospitalization.METHODSThe study was terminated early due to poor recruitment with 18 of the planned 70 patients enrolled. UC patients hospitalized for moderate–severe flares (Mayo score ≥6, endoscopic sub-score ≥2) were block randomized to steroids + daily HBOT (n = 10) or steroids + daily sham hyperbaric air (n = 8). Patients were blinded to study assignment, and assessments were performed by a blinded gastroenterologist. Primary outcome was the clinical remission rate at study day 5 (partial Mayo score ≤2 with no sub-score >1). Key secondary outcomes were: clinical response (reduction in partial Mayo score ≥2, rectal bleeding sub-score of 0–1) and progression to second-line therapy (colectomy or biologic therapy) during the hospitalization.RESULTSA significantly higher proportion of HBOT-treated patients achieved clinical remission at study day 5 and 10 (50 vs. 0%, p = 0.04). HBOT-treated patients less often required progression to second-line therapy during the hospitalization (10 vs. 63%, p = 0.04). The proportion requiring in-hospital colectomy specifically as second-line therapy for medically refractory UC was lower in the HBOT group compared to sham (0 vs. 38%, p = 0.07). There were no serious adverse events.CONCLUSIONIn this small, proof-of-concept, phase 2A trial, the use of HBOT as an adjunctive therapy to steroids for UC patients hospitalized for moderate–severe flares resulted in higher rates of clinical remission, and a reduction in rates of progression to second-line therapy during the hospitalization. Larger well-powered trials are needed, however, to provided definitive evidence of therapeutic benefit.

We aimed to develop and validate a classifier model to discriminate bacterial from viral infection in ulcerative colitis with opportunistic infections (UC-OI) by evaluating potential transcript signature in peripheral blood. The study comprised UC patients with bacterial or viral infection or without opportunistic infections. We screened for differentially expressed genes associated with bacterial or viral infections ( , and ) and compared the expression levels of the genes in different infection subgroups. Subsequently, UC patients were randomly assigned (1:1) to either the discovery or validation groups. We developed a binary logistic regression model integrating the expression of candidate genes using discovery group and evaluated its discriminatory performance in validation group. The expression levels of candidate genes differed significantly among infection subgroups. The and combination was the most discriminatory and was used to construct the model. The two-transcript classifier model had an AUC of 0.867 (95% CI 0.794-0.941) to discriminate bacterial and viral infections in the validation group. Its performance was better than that of PCT, CRP and ESR and was less affected by pathogen type. and transcript levels are robust classifiers to discriminate bacterial from viral infection in UC-OI, and measuring its levels appears to be predictive infection progression and treatment outcome in UC patients over time.

Current biomarkers in ulcerative colitis (UC) are limited by their performance, cost, and limited availability in daily practice. This study examined alterations in the leukocyte profiles as biomarkers of UC activity, including the effects of age, gender, and medications.MethodsCase–control study that included 110 UC subjects, 75 subjects with Clostridium difficile infection, and 75 non-inflammatory bowel disease (IBD) subjects, randomly selected from a single-institution IBD database. Mean values of neutrophils (N), lymphocytes (L), monocytes (M) and their ratios were compared between groups. Receiver operator curve analyses assessed the performance of each biomarker in discriminating disease states. Subgroup analyses examined leukocytes profiles with endoscopic activity.ResultsElevated monocyte counts and decreased L/M values significantly differed between subjects with active UC and UC in remission and performed better than the other leukocyte profiles. A monocyte count of 483 and L/M ratio of 3.1 were 60% sensitive and had a specificity of 61% and 53%, respectively for active UC. Monocyte count >860 and L/M value <1.6 had a 75% positive predictive value for UC activity. Those markers also correlated with endoscopically active disease. L/M and N/L values performed best at differentiating active UC from non-IBD controls, whereas N/L and N values performed best at differentiating from C. difficile controls.ConclusionsMonocytosis and a low L/M ratio might be effective, readily available, and low-cost biomarkers to identify disease activity in UC patients. N/L values were more effective in distinguishing active UC patients from patients without IBD and those with C. difficile infection.

•Effect of vitamin A supplementation on disease activity in patients with ulcerative colitis was studied.•There were significant differences between two groups regarding the mayo clinic score and subscores.•Compared with placebo group, clinical response and mucosal healing were significantly higher in vitamin A-supplemented group.•At 2 months, the NNT [95%CI] values for clinical response was 3 (2–40) and for mucosal healing was 5 [2.90–10.4]. Considering the link between vitamin A deficiency and disease activity in ulcerative colitis (UC) and also the association between dietary intake of vitamin A and gastrointestinal symptoms in these patients, this study aimed to investigate the effect of vitamin A supplementation on disease activity in patients with UC. In the present double-blind randomized controlled clinical trial, one hundred and fifty patients with Mayo score of 6–12 were randomly assigned to receive 25,000 IU/day vitamin A supplements or placebo for two months. The disease activity was calculated by the Mayo clinic score. Within groups and between groups comparisons were performed using paired sample t-test and one-way ANCOVA respectively. For measuring the treatment effect, the response ratio and number needed to treat (NNT) was calculated for the rate of clinical response and mucosal healing. One hundred and forty three patients completed the study. After two months of supplementation, significant decreases in Mayo clinic score (p < 0.001) and subscores (p < 0.001) was observed in the intervention group. There were significant differences between the two groups regarding Mayo clinic score and subscores after adjusting for age, sex, BMI, disease duration and baseline values (P < 0.05). Moreover, there were significant differences between two groups regarding clinical response ratio (P < 0.001) and mucosal healing ratio (P < 0.001). The NNT [95%CI] values for the clinical response was 3 [2–40] and for the mucosal healing was 5 [2.90–10.4]. Although according to the results, daily dose of 25,000 IU vitamin A had positive clinical and endoscopic effects, considering the limitations, further studies with longer duration and larger sample size and considering dietary intake are needed to confirm these preliminary results.