Journal of Crohn's & colitis最新文献

Background: Barrier healing is an emerging therapeutic target in inflammatory bowel disease (IBD), though its assessment remains challenging. We evaluated automated advanced imaging for real-time barrier assessment, its correlation with epithelial/vascular barrier markers, and ability to predict adverse outcomes.

Methods: IBD patients and healthy controls undergoing endoscopic assessment were prospectively enrolled. The intestinal barrier was evaluated using ultra-high-magnification endocytoscopy and probe-based confocal laser endomicroscopy. Targeted biopsies were obtained from inflamed and non-inflamed segments. Epithelial and vascular barriers were assessed through automated multiplex immunofluorescence for Claudin-2, ZO-1, E-cadherin, PV-1, and CD31. Gene expression profiling was performed in epithelial and lamina propria compartments. Artificial intelligence (AI)-based analysis was employed for automated evaluation of barrier features captured by advanced imaging.

Results: In total, 103 patients were included (38 ulcerative colitis [UC], 54 Crohn's disease [CD], 11 healthy controls). Advanced imaging revealed barrier healing in 21% (8/38) of UC and 30% (16/54) of CD patients. In UC, Claudin-2 moderately correlated with abnormal crypt architecture (ρ = 0.49), goblet cell depletion (ρ = 0.5), and overall endocytoscopy activity (ρ = 0.49). In CD, PV-1 moderately correlated with altered blood flow (ρ = 0.41) and vessel architecture (ρ = 0.40). An integrated assessment of advanced imaging, combined with Claudin-2 and PV-1 expression, effectively predicted adverse outcomes in UC and CD, respectively. AI tools accurately classified epithelial and vascular barrier features captured by advanced imaging. Finally, gene expression confirmed upregulation of Claudin-2 and PV-1 in IBD.

Conclusion: Automated advanced imaging enables real-time barrier assessment in IBD and correlates with markers of epithelial and vascular barrier impairment. AI integration can enhance standardization toward broader clinical applicability.

Background and aims: Adalimumab and ustekinumab are approved for the treatment of moderately to severely active Crohn's disease (CD); however, comparative data assessing the mechanism of action of tumor necrosis factor (TNFα) and interleukin (IL)-12/23p40 blockade in a head-to-head, double-blind CD trial are not available. Here we compared inflammatory serum proteins of biologic-naive patients with moderately to severely active CD treated with adalimumab or ustekinumab who participated in the SEAVUE trial (NCT03464136).

Methods: Serum from CD patients receiving adalimumab (n = 195) or ustekinumab (n = 191), and from a separate cohort of healthy controls (n = 40) was evaluated with a targeted inflammation panel, and a high sensitivity IL-22 assay. Differences in temporally regulated proteins were assessed at Weeks 16 and 52 in the context of study endpoints including clinical and endoscopic response.

Results: Expression levels of 79 inflammatory proteins were reliably measured in serum. At Week 0, before receiving study intervention, the overall cohort had similar serum proteomic expression profiles. At Weeks 16 and 52, following treatment with adalimumab or ustekinumab, distinct changes in serum proteins associated with inflammation were observed, including broader suppression of inflammation-related proteins by adalimumab and a reduction of IL-22 observed only with ustekinumab. Reduction of interferon-γ levels by ustekinumab at Week 52 was greater than by adalimumab and associated with a decrease in fatigue.

Conclusions: Although patients receiving either adalimumab or ustekinumab reached similar rates of clinical remission at Week 52, the two therapies resulted in unique serum proteomic expression profiles, reflecting mechanistic differences. Long-term treatment data are necessary to understand how differences in therapeutic mechanisms are associated with maintenance of remission and changes in patient-reported outcomes in the context of inflammatory biomarkers.

Background and aims: The benefit of continuing 5-aminosalicylates (5-ASA) in patients with ulcerative colitis (UC) escalated to advanced therapies remains uncertain. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of 5-ASA continuation vs discontinuation in this population.

Methods: We systematically searched the PubMed, Embase, and Cochrane databases for studies comparing 5-ASA continuation vs discontinuation in adult patients with UC escalated to advanced therapies. Adjusted effect estimates were pooled using random-effects models.

Results: The meta-analysis comprised nine observational cohorts and two studies presenting post-hoc analyses from eight clinical trials. We included 11 487 patients, with 9105 assigned to 5-ASA continuation and 2382 to 5-ASA discontinuation. Compared to discontinuation, 5-ASA continuation was associated with decreased odds of achieving clinical remission (adjusted odds ratio [aOR] 0.72; 95% CI 0.52-0.99; I2 = 0%). There were no significant differences between groups for corticosteroid-free clinical remission (aOR 0.71; 95% CI 0.41-1.23; I2 = 0%), clinical response (aOR 0.94; 95% CI 0.69-1.28; I2 = 0%), endoscopic healing (OR 1.00; 95% CI 0.71-1.41; I2 = 54.6%), and biochemical remission (aOR 1.13; 95% CI 0.76-1.68; I2 = 31%). In time-to-event analyses, no significant differences were found between groups for UC-related hospitalization (adjusted hazard ratio [aHR] 0.99; 95% CI 0.86-1.13; I2 = 0%), UC-related surgery (aHR 1.02; 95% CI 0.80-1.29; I2 = 13%), new corticosteroid prescription (aHR 0.97; 95% CI 0.88-1.07; I2 = 0%), composite adverse events (aHR 0.96; 95% CI 0.87-1.06; I2 = 0%), and loss of response (aHR 0.92; 95% CI 0.75-1.12; P = .39; I2 = 61%).

Conclusion: In patients with UC escalated to advanced therapies, 5-ASA continuation was associated with decreased odds of achieving clinical remission compared to discontinuation, with no significant differences observed for secondary efficacy or safety endpoints.

Background: The TOpClass classification for perianal fistulizing Crohn's disease (pfCD) facilitates tailored treatment to clinical state and patient goals. MRI is central to pfCD assessment, but existing indices are limited in predicting disease classification and trajectory. This study evaluated MRI fistula volume as a radiological biomarker and its longitudinal association with pfCD class.

Methods: We conducted a retrospective cohort study of 51 consecutive pfCD patients who underwent a baseline pelvic MRI in 2010 with ≥1 follow-up MRI. pfCD class was assigned at baseline, short- and long-term follow-up (median 10 years). A gastrointestinal radiologist, blinded to clinical data, measured active MRI fistula volume on T2-weighted axial sequences at each timepoint using ITK-Snap. The primary outcome was the association between volume and pfCD Class. Secondary outcomes included identification of volume thresholds discriminating clinical state/class via ROC analysis.

Results: Of 51 included patients (mean age 34.5), the majority had complex fistulae (92.1%) and 71% patients were TOpClass 2b, with 35% changing class during follow-up. MRI fistula volume measurement was feasible (median acquisition time 207 seconds, IQR 116-250). Volume was associated with disease severity, increasing across TOpClass strata (P < .001). ROC-derived volume thresholds effectively differentiated classes (AUROC 0.69-0.80). A ≥ 27% volume reduction was associated with clinical improvement (AUROC 0.78; sensitivity 64%, specificity 84%).

Conclusions: MRI fistula volume is associated with pfCD class and disease trajectory. Volume thresholds are associated with classification shifts and clinical response, supporting their potential as objective quantitative tools. Prospective multicenter validation is warranted.

Background and aims: A reduction of bowel wall thickness (BWT) on intestinal ultrasound (IUS) predicts endoscopic response in ulcerative colitis (UC). Advanced techniques such as shear-wave elastography (SWE) might enhance response assessment. We aimed to identify early IUS parameters to predict treatment response to filgotinib in UC.

Methods: This prospective observational study included UC patients with endoscopically active disease (endoscopic Mayo score [EMS] ≥2, extending beyond the rectum) starting on filgotinib. IUS parameters, including SWE, were assessed at baseline (T0), week 4 (T1), and at second endoscopy (T2). EMS of both the most-affected segment and the sigmoid was assessed at T0 and T2, and endoscopic response was defined a ≥1 point decrease in EMS.

Results: A total of 23 patients were included. Six of 21 patients who underwent a second endoscopy were endoscopic responders. At T1 in the sigmoid, a BWT decrease of ≥1.33 mm or ≥24.7% (odds ratio [OR]: 32.5 [2.4-443.2], P = .009 and OR: 13.8 [1.2-156.6], P = .035) and submucosa decrease of ≥20.8% (OR: 13.8 [1.2-156.6], P = .035) predicted endoscopic response. Additionally, color Doppler signal (CDS) improvement at T1 predicted endoscopic response (OR: 20.0 [1.7-241.7], P = .018). In the sigmoid, SWE values changed differently over time between responders and non-responders (T2: 9.9 ± 15.7 vs -8.1 ± 11.4 kPa, P = .002). However, SWE values at T1 were not predictive of endoscopic response (OR: 1.07 [0.99-1.16], P = .088).

Conclusions: On IUS, BWT, submucosal thickness, and CDS predict endoscopic response after 4 weeks of filgotinib treatment. SWE values in the sigmoid differ between responders and non-responders, but early assessment does not predict treatment response.

Background and aims: Pseudopolyps have traditionally been considered sequelae of mucosal healing in inflammatory bowel diseases (IBDs). However, recent retrospective studies suggest that pseudopolyps may harbor dysplasia or obscure neoplastic lesions. This prospective study aimed to assess the frequency of dysplasia in pseudopolypoid lesions endoscopically resected in IBD patients and to identify potential predictors of dysplasia.

Methods: We analyzed pseudopolypoid lesions resected during colonoscopies performed between June 2023 and March 2025 in patients with colonic IBD at a single tertiary center. Lesions macroscopically classified as pseudopolyps and completely resected were histologically analyzed and categorized as inflammatory pseudopolyps, inflammatory pseudopolyps with foci of epithelial dysplasia, conventional adenomas, or IBD-associated dysplasia. Multivariable logistic regression was used to identify predictors of dysplasia.

Results: Pseudopolyps were identified in 165 out of 910 patients undergoing colonoscopy (18.1%), and 124 lesions were resected in 98 patients. Dysplasia was detected in 15 lesions (12.1%), including conventional adenomas (53%, one with intramucosal carcinoma/high-grade dysplasia), IBD-associated dysplasia (20%), and hyperplastic lesions with dysplasia (27%). A heterogeneous pit pattern (OR = 4.50; 95% CI: 1.27-15.9) and absence of ulceration (OR = 0.093; 95% CI: 0.01-0.77) were independent predictors of dysplasia. No dysplasia was found in the surrounding mucosa.

Conclusions: Dysplasia was found in 12% of pseudopolypoid lesions, challenging the assumption that they are uniformly benign. Endoscopic features such as heterogeneous pit pattern and absence of ulceration may aid in identifying high-risk lesions. These results highlight the diagnostic uncertainty surrounding pseudopolyps in IBD and call for careful endoscopic assessment rather than routine resection.

Introduction: Ulcerative colitis (UC) is a chronic inflammatory disease that impairs health-related quality of life (HRQoL). We evaluated the effect of approved therapies on HRQoL in adults with moderate-to-severe UC.

Methods: We systematically searched Medline, Embase, CENTRAL, and gray literature through December 2024 for randomized controlled trials (RCTs) of approved therapies. The primary outcome was change in Inflammatory Bowel Disease Questionnaire (IBDQ) score during induction and maintenance. Secondary outcomes included changes in Short Form-36 (SF-36) Mental and Physical Component Scores, Work Productivity and Activity Impairment in UC (WPAI-UC), and rates of IBDQ response (≥16-point increase) and remission (score ≥170). Minimal clinically important differences were prespecified. Subgroup analyses based on prior biologic exposure were performed for primary outcome. Frequentist random-effects network meta-analyses were conducted, and confidence in estimates was assessed using the CINeMA (Confidence In Network Meta-Analysis) framework.

Results: Twenty-eight RCTs were included; 26 reported HRQoL outcomes during induction and 15 during maintenance. During induction, clinically meaningful improvements in IBDQ were observed with upadacitinib, filgotinib, and guselkumab. During maintenance, upadacitinib 30 mg and vedolizumab showed HRQoL benefits, although clinical meaningfulness was not consistently demonstrated. SF-36 improvements were modest overall, with upadacitinib and vedolizumab showing selective advantages, while WPAI-UC benefits were observed with upadacitinib, vedolizumab, and ustekinumab. Upadacitinib consistently ranked highest in IBDQ response and remission, while other therapies showed variable efficacy across outcomes.

Discussion: Advanced therapies vary in their impact on HRQoL, with some demonstrating clinically meaningful improvements in UC. These findings support integrating HRQoL into treatment selection and shared decision-making.

Background: Internalized stigma impacts the wellbeing of inflammatory bowel disease (IBD) patients and has complex relationships with experiences of discrimination and disease disclosure.

Methods: We surveyed 1263 IBD Partners e-cohort participants. Discrimination and internalized stigma were measured using the Everyday Discrimination Scale (EDS) and the Paradox of Self Stigma (PaSS-24) scale. IBD disclosure was measured using a modified "outness" scale.

Results: Overall, 48.8% of respondents reported discrimination, and there was a strong association between discrimination and internalized stigma (Pearson rho = 0.436, P < .001). Individuals who experienced discrimination were significantly more likely to be female, sexual or gender minorities (SGM), younger, and non-white. EDS score had a weak negative correlation with IBD disclosure (Pearson rho = -0.152, P< 0.001), indicating higher reported levels of discrimination correlated with lower rates of IBD disclosure. Internalized stigma was common and significantly associated with active disease (median PaSS-24 score 53 for respondents with active disease vs a score of 43 for respondents in remission; P < .001). Internalized stigma had a moderate negative correlation with disclosure of IBD (Pearson rho = -0.397, P < .001), indicating that more disease disclosure correlated with lower levels of internalized stigma. In a mediation analysis, disease disclosure was a significant mediator of the effect of discrimination on internalized stigma, mediating 15% of the overall estimated effect (P < .001).

Conclusions: In this large cohort of adults with IBD, experiences of discrimination and internalized stigma were common and associated with active disease. Disease disclosure may mediate the relationship between discrimination and internalized stigma. This emphasizes the importance of psychosocial support for individuals with IBD.

Background: Oral corticosteroids remain the treatment of choice for moderately active ulcerative colitis (UC), achieving clinical remission in 30%-60% of patients.

Objective: To compare the rates of steroid-free clinical-endoscopic remission at weeks 8 and 54 in patients treated with 3 methyl-prednisolone pulses before oral corticosteroids in moderately active UC versus those only receiving oral corticosteroids.

Design: Prospective, open, multicentre, randomized, controlled trial. Patients with left/extensive, moderately active UC, naive to immunosuppressants and biological agents, were randomized to receive conventional treatment (CT) with oral prednisone 60 mg/day or the same regimen preceded by an additional daily pulse (AP) of 500 mg of methyl-prednisolone for 3 days. All patients who responded started oral mesalazine and were followed up until month 12 or clinical relapse.

Results: Seventy-five patients were randomized: 39 were allocated to the CT arm and 36 to the AP arm. Overall, 21 patients achieved clinical-endoscopic remission (28%; 95% confidence interval [CI]: 23%-33%) at both weeks 8 and 54 without needing rescue treatments, being not significantly different between both study groups (23% [95%CI: 14%-32%] CT vs. 33% [95%CI: 21%-45%] AP; P = 0.323). Patients in the AP group had higher rates of clinical response at day 3 and remission at day 7. No significant differences in adverse events were observed. Due to early termination, the study was underpowered, and findings should be interpreted as exploratory.

Conclusions: The addition of 3 pulses of high-dose corticosteroids to a conventional regimen of oral prednisone does not improve medium and long-term clinical outcomes in moderately active UC.

Trial registration codes: EudraCT number 2016-001170-15; ClinicalTrials.gov identifier NCT02921555.