Journal of Crohn's & colitis最新文献

Background: We aimed to assess the risk of serious infections in patients with inflammatory bowel disease (IBD) exposed to different advanced therapies.

Methods: We linked nationwide registers and compared rates of incident serious infections in patients with Crohn's disease (CD) and ulcerative colitis (UC) exposed to medical therapies versus matched general population comparators during 2007 to 2023. We 1:1 propensity score-matched individuals with IBD to compare infection risk across therapies.

Results: We identified 55,866 patients with IBD naïve to immunomodulators (IMM) and advanced therapies, 20,392 exposed to IMM, 15,973 to anti-TNF, 9035 to IMM with anti-TNF, 3948 to vedolizumab, 2926 to ustekinumab, 659 to tofacitinib, 987 to upadacitinib, 262 to filgotinib, and 163 to risankizumab with 987,366 matched comparators with up to 18 years of follow-up. Compared to the general population [incidence rate range 0.39-1.13 per 100 person-years (PY)], patients with IBD had a higher incidence of serious infections [naïve 2.31 per 100 PY; adjusted hazard ratio (aHR) 1.89, 95% Confidence Interval (CI) 1.84-1.94], IMM 3.27 per 100 PY (aHR 4.45 95% CI 4.24-4.66), advanced therapies range 3.14-8.10 per 100 PY (aHRs range 3.45-10.55, 95% CI range 3.04-26.65). Relative risks were elevated in the pediatric population, and for opportunistic and gastrointestinal infections. No differences in infection rates were observed in propensity score-matched comparisons of different advanced therapies.

Conclusion: Patients with IBD were at an increased risk of infections, even among those naïve to IMM and advanced therapies. There was no significant difference in risk of infections across advanced therapy exposures.

Background: Crohn's disease (CD) is characterized by chronic intestinal inflammation. Previous single-cell transcriptomic studies have mostly focused on established disease, leaving a knowledge gap in relation to treatment-naive profiles across multiple regions of the gut.

Methods: To study disease onset, a treatment naïve pediatric CD cohort was recruited, and single-cell transcriptomics was performed on ileum, colon, and rectum biopsies collected at initial endoscopy. A clustering stability assessment workflow was developed to ensure clustering and downstream results were robust.

Results: Inflammation did not strongly influence cellular proportion due to heterogeneity across donor and tissue. Tensor decomposition revealed distinct mesenchymal and myeloid cell-mediated sources of disease pathology, corresponding to previously identified fibrotic and pro-inflammatory disease progression. Integrating transcriptomics and genome wide association summary statistics for CD suggested myeloid and T cells drive disease, highlighting potential cellular therapeutic targets.

Conclusion: Tensor decomposition stratified donors into clinically meaningful groups based on their transcriptomic profile, suggesting these signatures can be utilized for personalized medicine.

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: 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: 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 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.

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: 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.