Inflammatory Bowel Diseases最新文献

Background: Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC). However, the chemopreventive role of aspirin remains uncertain due to conflicting findings in prior studies.

Methods: The study sought to evaluate the association between long-term aspirin use and the risk of CRC and all-cause mortality in patients with IBD. We conducted a nationwide propensity score-matched cohort study using Taiwan's National Health Insurance Research Database and Cancer Registry from 2008 to 2022. Time-dependent Cox models and Fine and Gray competing risk models were applied.

Results: Among 2743 matched aspirin users and 2743 nonusers, aspirin use was associated with reduced CRC risk (adjusted hazard ratio, 0.42; 95% confidence interval, 0.31-0.57) and lower all-cause mortality (adjusted hazard ratio, 0.66; 95% confidence interval, 0.58-0.74). A dose-response relationship was found for cumulative exposure, while optimal daily intensity was near 80 mg/d.

Conclusions: Long-term use of low-to-moderate-dose aspirin was associated with reduced risks of CRC and mortality in patients with IBD. These findings support aspirin's potential as a chemopreventive agent and justify further randomized trials.

Background: Golimumab is an anti-TNFα biologic agent that has been approved for adults with moderately-to-severely active ulcerative colitis (UC). We investigated the efficacy, safety, and pharmacokinetics (PK) of golimumab in biologic-naïve children with moderately-to-severely active UC.

Methods: The prospective, multicenter, open-label PURSUIT 2 study enrolled biologic-naïve children (2 to <18 years) with moderately-to-severely active UC (Mayo score 6-12; endoscopic subscore ≥2) despite conventional treatment. During the 6-week induction phase, patients received subcutaneous (SC) golimumab dosed by weight (<45 kg: 120/60 mg/m2; ≥45 kg: 200/100 mg) at weeks 0/2. Week 6 clinical responders (Mayo score decrease from baseline ≥30% and ≥3 points, with either a decrease in the rectal bleeding subscore of ≥1 or a rectal bleeding subscore of 0/1) continued golimumab dose q4w during the 48-week maintenance phase. The primary endpoint was clinical remission (Mayo score ≤2 points with no individual subscore >1) at week 6. Efficacy and PK data are presented alongside a reference adult UC population who received golimumab SC 200/100 mg at weeks 0/2 and 100 mg q4w thereafter.

Results: Of the 69 patients (mean age, 13.4 ± 3.3 years) enrolled, 31.9% (22/69) were in clinical remission at week 6, and of those, 54.5% (12/22) remained in clinical remission at week 54. At week 54, 31.7% (13/41) of week 6 clinical responders achieved clinical remission. Additionally, 33.3% achieved clinical remission by the Pediatric Ulcerative Colitis Activity Index (PUCAI), 56.5% clinical response by Mayo, 40.6% endoscopic improvement, and 7.2% endoscopic remission at week 6. Of those who were clinical responders at week 6, 34.1% achieved clinical remission by PUCAI, 31.7% corticosteroid-free clinical remission by Mayo, 36.6% endoscopic improvement, and 9.8% endoscopic remission at week 54. Serum golimumab concentrations through week 6 were comparable to the reference adult UC population. Through week 54, 40.6% reported serious adverse events and 13.0% serious infections. No new safety concerns were identified.

Conclusions: Overall, the results of the PURSUIT 2 study support golimumab treatment for children with moderately-to-severely active UC. ClinicalTrials.gov ID: NCT03596645.

Background: We examined real-world utilization of treat-to-target (TTT) strategies and conducted a quality improvement (QI) project to improve uptake of TTT strategies in a learning health system, IBD Qorus.

Methods: We implemented a structured QI intervention to increase uptake of TTT in 41 gastroenterology practices in the United States, over a 13-month intervention period (November 2020 to November 2021; modified breakthrough series [BTS] collaborative), and a 10-month post-BTS observation period (December 2021 to October 2022). Through encounter-level surveys, we examined providers' "intention to TTT" based on discussion of TTT with patients, documentation of inflammation, and intention to change therapy to TTT. We examined changes in rates of "intention to TTT," and whether improvement in intention to TTT influenced site-level rates of remission.

Results: Over 13 months, there were 7932 patient visits (55% with Crohn's disease; 47% in clinical remission); patients in 2160 visits (27%) were not in endoscopic remission. Overall, rates of intention to TTT increased from 31% to 54% (P = .06) with considerable site-to-site variability and was maintained at 49% in the post-BTS observation period. The increased rate was attributable to higher rates of testing for inflammation. Despite an increase in the rate of intention to TTT, there was no significant change in site-level achievement of remission over the same time.

Conclusions: Through a QI initiative in a learning health system, rates of intention to TTT increased significantly over 12-months, though overall rates remained low. Assessing patient-, provider- and practice-level barriers and facilitators for successful implementation of a TTT strategy is warranted to improve clinical outcomes.

Autophagy is a crucial cellular process involved in the degradation of cytoplasmic components through lysosomal machinery. It is essential for maintaining cellular homeostasis and responding to various stressors. Autophagy has emerged as a key regulator of immune responses, particularly in the context of chronic inflammatory diseases, such as inflammatory bowel diseases and cancer. Increasing evidence highlights its dual role in both exacerbating and controlling inflammation, depending on the disease context. This review critically examines the molecular mechanisms of autophagy, its regulation within immune cells, and its complex involvement in chronic inflammation. We explore how dysregulated autophagic processes contribute to disease pathogenesis, with particular focus on inflammatory bowel disease and how these conditions increase cancer risk. Furthermore, we discuss the potential of autophagy modulation as a therapeutic strategy for these diseases. Current therapeutic approaches targeting autophagy are reviewed, alongside emerging strategies and their clinical implications. This comprehensive analysis underscores the importance of understanding the multifaceted roles of autophagy in immune regulation, with the aim of advancing therapeutic interventions for inflammatory and cancer-related conditions.

Background: The Mayo endoscopic score (MES) provides a criterion-based, but still subjective, human assessment of endoscopy and related endpoints in therapeutic clinical trials in ulcerative colitis (UC). A novel solution to address issues of reproducibility is the use of machine learning (ML) models to standardize MES evaluations. Broader applicability of this solution requires an understanding of the models and related performance characteristics. The objective of this study is to provide a systematic review on training and testing of ML MES prediction models on full-length endoscopic videos from patients with UC.

Methods: PubMed/MEDLINE, EMBASE, and Web of Science were systematically searched on December 31, 2024, and supplemented by reference checks and Google search to identify studies on training or testing of ML models to produce an automated MES grade on endoscopic procedure videos in UC.

Results: A total of 7 studies met the inclusion criteria, and of those, 5 were eligible for reporting on model performance. Accuracy in predicting ordinal MES grades (0, 1, 2, 3) ranged from 56.8% to 83.3%. Accuracy in predicting MES 0, 1 vs 2, 3 and MES 0 vs 1, 2, 3 (each aligned with a definition of endoscopic improvement and remission in trials) ranged from 84% to 90.2% and from 90% to 95.5%, respectively.

Conclusions: Our review demonstrates strong performance characteristics of ML models to assess the MES on endoscopic videos in UC, potentially offering a standardized and reproducible solution to measure endoscopic severity. Further research will investigate the impact of this technology on clinical trial outcomes.

Background: Poor sleep is common in Crohn's disease (CD), prospectively predicts worse disease course, and is often attributable to insomnia. Cognitive behavioral therapy for insomnia (CBT-I) is the recommended treatment for chronic insomnia disorder. CBT-I improves sleep and may improve pain intensity, pain interference, and inflammation. We sought to investigate whether CBT-I impacts these factors in patients with active CD.

Method: We recruited patients with insomnia and mild-to-moderate CD symptoms from an inflammatory bowel disease center. Exclusion criteria were other sleep disorders, significant psychiatric concerns, and presence of other common influences on sleep. Participants completed baseline assessments of sleep, pain, and inflammation then were randomized to receive CBT-I immediately, or wait 12 weeks and then repeat the baseline assessment and complete CBT-I. Similar assessments occurred immediately post-CBT-I and 1 month later. CBT-I included sleep restriction, stimulus control, sleep hygiene, arousal reduction, and cognitive therapy.

Results: A total of 26 participants completed the study. In group × time analyses, CBT-I led to greater reductions in insomnia severity (P < .001) and wake after sleep onset (P = .02) than waitlist. In pre- to post-treatment analyses, participants reported significant improvements in subjective measures of sleep continuity, CD symptom severity, pain intensity, and pain interference. C-reactive protein trended toward improvement.

Discussion: This study provides preliminary evidence of efficacy of CBT-I in people with CD. CBT-I improved self-reported sleep and may improve pain and CD symptoms. The results highlight the importance of addressing sleep concerns in inflammatory bowel disease, particularly in people with persistent pain or fatigue. Future trials powered to detect changes in pain and inflammation are warranted.

Background: The diagnosis of microscopic colitis (MC) is based on endoscopic biopsy with histological assessment. Histological outcomes (remission, response or improvement) are important treatment targets in clinical trials. Although a substantial body of research on MC has been published in recent years, no standardized criteria currently exist for its histological outcomes. We sought to review and summarize the histological evaluation of MC in published systematic reviews (SRs) assessing the efficacy of interventions and to examine the heterogeneity in histological evaluation among the randomized controlled trials (RCTs) included in those SRs.

Methods: We conducted an umbrella review (ie, an overview of systematic reviews) of published SRs. A literature search of the Cochrane Database of Systematic Reviews, MEDLINE, and Embase was performed up to May 2025. Definitions of histological evaluation and monitoring following interventions were extracted and summarized from the published SRs and the RCTs included within them.

Results: Fourteen SRs with meta-analyses that focused on interventions were included. Nineteen RCTs were included in these SRs. Of them, 12 fully published RCTs reported histological outcome data and met our inclusion criteria. The definitions for histological outcomes varied between RCTs but were generally based on reduction in lamina propria cellularity, intraepithelial lymphocytes, or collagen band thickness.

Conclusions: This umbrella review highlights the heterogeneity in the definitions of histological outcomes in MC RCTs. The summarized evidence will support ongoing efforts to develop consensus definitions for histological outcomes in order to facilitate clinical trials of medical therapies for MC.

Background: There is lack of data regarding the associations between perianal fistulizing disease and other disease characteristics at diagnosis in children with Crohn's disease (CD). We sought to investigate the associations between perianal fistulizing disease and other disease characteristics at diagnosis in children with CD.

Methods: This was a multicenter, registry-based, inception cohort study conducted in Korea. Children newly diagnosed with CD were included. Baseline clinicodemographics; results from laboratory, endoscopic, histologic exams; and Paris classification factors were collected, and associations between factors were investigated.

Results: A total 699 patients were included. The median age at diagnosis was 14.3 years (IQR, 12.3-15.9 years), and the male-to-female ratio was 2.66:1. Perianal disease modifiers comprised 50.6% (n = 354 of 699) of the patients. The proportion of perianal disease modifiers was higher in males (81.1% vs 64.1%; P < .001), in those with upper gastrointestinal tract involvement (85.3% vs 75.7%; P = .002), and in those with B1 behavior (89.5% vs 79.7%; P < .001). Albumin was higher (P = .006) and CRP was lower (P < .001) in patients with perianal disease modifiers. Females had a higher proportion of B2/B3 behavior (21.4% vs 14.4%; P = .029), higher Pediatric Crohn's Disease Activity Index scores (median 40 vs 32.5; P < .001), higher CRP (P = .017), higher Simple Endoscopic Score for Crohn's Disease scores (P = .01), and more frequent detection of noncaseating granulomas in the lower gastrointestinal tract (P = .008).

Conclusions: Perianal fistulizing disease was more common in boys who exhibited milder disease activity, indicating the importance of recognizing perianal fistulizing disease as a clinical clue to the early diagnosis of underlying luminal CD.