Journal of Crohn's & colitis最新文献

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: 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.

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 and aims: Loss of response (LoR) is a major limitation of anti-tumor necrosis factor (anti-TNF) therapy in inflammatory bowel disease (IBD). It can result from immunogenicity or other, less well-defined mechanisms. Specific HLA alleles have been linked to immunogenicity, but their association with LoR are not fully understood. In this study, we aimed to assess the relationship between HLA alleles and LoR, and investigate the impact of concomitant immunomodulator use.

Methods: LoR and sustained response to infliximab or adalimumab were defined in 25 642 IBD patients from the IBD BioResource. We applied multivariable Cox proportional hazards models to assess the effect of HLA alleles on time to LoR. The effect of concomitant immunomodulator use was also evaluated. Significantly associated alleles were further tested in patients treated with ustekinumab and vedolizumab.

Results: HLA-DQA1*05:01 was associated with reduced time to LoR in infliximab-treated patients (P = 5.34E-07), while HLA-DQA1*05:05 was associated with reduced time to LoR in adalimumab-treated patients (P = 3.20E-05). Neither allele was associated with LoR to ustekinumab or vedolizumab. Concomitant use of immunomodulators conferred a protective effect against LoR to infliximab and adalimumab in carriers of HLA-DQA1*05:01 and HLA-DQA1*05:05, respectively. However, this protective effect was not observed in adalimumab-treated patients who carried neither allele subtype (P = .11).

Conclusions: Our findings highlight distinct associations between HLA-DQA1*05 allele subtypes and time to LoR of infliximab and adalimumab in IBD-treated patients. The protective effect of immunomodulator use is allele-specific for adalimumab. These results provide a rationale for incorporating HLA testing into personalized anti-TNF management to optimize treatment durability.

Background: Disease duration is associated with lower treatment response and accrual of bowel damage in Crohn's disease (CD), but not in ulcerative colitis (UC). We aimed to understand intestinal transcriptomic changes associated with disease duration in CD and UC.

Methods: We analyzed intestinal tissue RNA sequencing data from two independent prospective cohorts of CD and UC patients, the Mount Sinai Crohn's and Colitis Registry (MSCCR; nCD = 498, nUC = 421), and the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD; nCD = 777, nUC = 440). We conducted differential expression analysis and subsequent pathway analyses of significantly up- or down-regulated genes, and examined cell type-specific expression of significant genes and pathways in ileal single-cell RNA sequencing data from CD patients (n = 18). We then assessed the association of significant pathways with treatment response in an infliximab-treated CD cohort.

Results: Significantly more genes were differentially expressed with increasing disease duration in CD compared to UC in both cohorts (MSCCR: nCD = 1472, nUC = 227; SPARC: nCD = 1248, nUC = 25; q-value < 0.05). A shared gene signature with 263 down- and 135 up-regulated genes in longer standing disease was identified. Pathway analyses revealed significant enrichment in pathways related to oxidative phosphorylation, mitochondrial dysfunction, cholesterol biosynthesis, liver X receptor/retinoid X receptor (LXR/RXR) activation, and protein modifications. Pre-treatment intestinal gene expression of four disease duration-related pathways were associated with non-response to infliximab.

Conclusion: Disease duration influences intestinal gene expression in CD but significantly less so in UC. The identified pathways and genes may inform development of differing biomarkers and treatment strategies in shorter versus longer standing CD.

Background: Placebo response rates in ulcerative colitis (UC) trials are highly variable. It is uncertain whether adding objective measures of inflammation, such as fecal calprotectin (FC) or histologic activity, to conventional eligibility criteria could reduce placebo response and strengthen treatment effect estimates. This study evaluated whether applying baseline FC or histology thresholds would alter outcomes in UC clinical trials.

Methods: We conducted a post-hoc pooled analysis of individual patient-level data from five phase 3, randomized, placebo-controlled trials including 1918 patients on active therapy and 1149 on placebo. Baseline FC thresholds (>150, >200, >250, >500 µg/g) and Geboes histological thresholds (≥3.1, ≥3.2) were applied as hypothetical inclusion criteria. Outcomes assessed were post-induction clinical remission (CR: modified Mayo score with stool frequency ≤1 and ≥1-point decrease, rectal bleeding = 0, and endoscopic subscore ≤1) and endoscopic improvement (EI: endoscopic subscore ≤1).

Results: Applying FC or Geboes thresholds did not meaningfully reduce placebo response rates or increase treatment-placebo differences for CR or EI. For example, for vedolizumab, the CR difference vs placebo was 11% (95% CI: 3.5-18.5) in the unrestricted population and 10.4%-13% with thresholds applied, with up to 91 (33.6%) of participants excluded. For upadacitinib, EI differences were 36.2% (95% CI: 28.5-43.8) unrestricted and 35.9%-37.3% with restrictions, with up to 248 (38.7%) of participants excluded. Results were consistent across therapies and in subgroup analyses.

Conclusion: Restricting trial enrollment based on elevated FC or histological activity did not meaningfully lower placebo response rates in phase 3 UC trials.