Journal of Crohn's & colitis最新文献

Introduction: While ileocolic resection is the most common surgical procedure for Crohn's disease (CD), many physicians prefer to initiate pharmacotherapy before considering surgery. This study aimed to compare early ileocolic resection (EICR) with medical treatment (MT) for localized ileocolic CD.

Methods: A systematic search was conducted across PubMed, Cochrane, Embase, and Google Scholar. Inclusion criteria required studies to compare EICR (performed within 18 months of initial diagnosis) without the use of biologics to MT, with primary outcomes being the need for CD-related surgery and the use of biologics.

Results: Five studies involving 1770 patients, both pediatric and adult, were included in this analysis. The data showed that in the EICR cohort, which comprised 740 patients, the rate of CD-related surgery within 5 years of initial treatment was 2.43%. In contrast, the MT cohort, consisting of 1030 patients, had a much higher surgery rate of 20.58% (P < 0.001). Additionally, at a mean follow-up of 5 years, the long-term use of biologics was significantly lower in the EICR cohort compared to the MT cohort, with rates of 18.38% and 72.91% respectively (P < 0.001).

Conclusion: An EICR operation for localized ileocolic CD was associated with longer and more stable remission, resulting in improved long-term outcomes compared to medical therapy alone. In cases of localized ileocolic CD where MT fails to improve disease activity after several months, early surgical intervention may provide a safe and effective way to achieve disease remission and enhance the overall quality of life for patients.

Objective: Identifying proteomic signatures in treatment-naïve individuals newly diagnosed with inflammatory bowel disease (IBD) may provide insights into the underlying pathophysiological mechanisms of the disease and aid in distinguishing Crohn's disease (CD) from ulcerative colitis (UC).

Design: In the discovery phase, label-free quantitative proteomics was performed to analyze proteomic profiles in serum extracellular vesicles (EVs), serum, urine, and intestinal tissue from 100 newly diagnosed IBD patients (50 CD and 50 UC), and 51 healthy controls (HC). Serum candidate biomarkers were validated using ELISA in a separate subset cohort (87 CD, 134 UC, and 99 HC), and immunohistochemistry was performed on biopsies from the discovery cohort to confirm findings.

Results: We identified 419 proteins in serum EVs, 468 in serum, 683 in urine, and 2603 in intestinal tissue. ELISA results showed lower levels of TTR and APOC3 and higher levels of ATRN in UC patients compared to HC. Similarly, CD patients showed lower TTR and higher ATRN levels compared to HC. Moreover, serum protein S10A9 was differentially upregulated in CD vs UC. Immunohistochemistry revealed increased PRDX4 and AZU1 expression in the ileum of CD patients, whereas AOFB expression was lower in the ileum of CD and in the left colon of both CD and UC compared to HC.

Conclusion: This comprehensive proteomic study has identified a set of proteins differentially expressed in IBD, which may contribute to a better understanding of its mechanisms and hold promise as candidate biomarkers. Although these findings are preliminary, they warrant further investigation to evaluate their diagnostic and therapeutic relevance.

Background: Upper gastrointestinal Crohn's disease (UGICD) is an uncommon phenotype with limited management guidelines. We reviewed evidence on the safety and efficacy of pharmacological interventions for UGICD.

Methods: We searched MEDLINE, Embase, and Cochrane CENTRAL (1990-2025) for randomized controlled trials (RCTs) and comparative observational studies evaluating pharmacological or dietary interventions for UGICD, including esophagus to jejunum. Two reviewers screened studies, extracted data, and assessed bias (Newcastle-Ottawa Scale). Primary outcomes were clinical remission and response. Due to limited, heterogeneous evidence, data are summarized descriptively.

Results: Of 1207 citations, 11 observational studies (nine retrospective, two prospective) and post-hoc analyses from two RCTs met the criteria, involving 387 patients. Most had ileocolonic involvement (280/387; 72.3%); only 8.5% (33/387) had isolated UGICD. Five studies (137 patients) reported esophageal CD. Follow-up ranged from 6 weeks to 28 years. Interventions and outcomes varied. Anti-tumor necrosis factor (anti-TNF) drugs and corticosteroids, alone or combined with other treatments, were associated with improvements in clinical outcomes, endoscopic healing, and histology, but controlled data are lacking. Other therapies, including proton pump inhibitors, H2-receptor antagonists, enteric nutrition, immunomodulators, anti-integrins, and anti-interleukin12/23, showed moderate to minimal improvement.

Conclusions: Our systematic review highlights a paucity of evidence to inform therapeutic strategies in UGICD. Positive outcomes were reported for corticosteroids and anti-TNF, but from small observational and uncontrolled studies. Data for most advanced therapies remain limited, highlighting a large unmet need to inform clinical practice.

Background: Randomized controlled trials (RCTs) provide high-quality evidence but often lack generalizability to real-world populations. Although real-world evidence (RWE) studies help to bridge this gap, retrospective design and heterogeneous outcome measures still limit their standardization in Crohn's disease (CD). Building on the recent ECCO Position Paper, this study aimed to identify the most relevant outcomes for real-world CD studies.

Methods: An international panel of inflammatory bowel disease (IBD) specialists participated in a structured two-round Delphi e-survey using the RAND/UCLA Appropriateness Method. Experts rated outcomes across eight domains, including disease activity, patient-reported outcomes, and treatment safety. Agreement was assessed using the Disagreement Index (DI), where DI > 1 indicated disagreement, and DI ≤ 1 indicated agreement or no disagreement. Weighted scoring prioritized key outcomes.

Results: A total of 51/85 experts (60%) completed Round 1 and 48/51 (94%) Round 2. No disagreement was observed (DI < 1) in both rounds. The highest-ranked outcomes were Abscess or Fistula (10.6%), Endoscopic Remission (10.3%), Corticosteroid-Free Clinical Remission (8.9%), Disease Progression (6.7%), and Colorectal Cancer (5.9%). The top 10 outcomes accounted for 61.5% of the weighted score. For combinations, the top four outcomes, Corticosteroid-Free Clinical Remission (16.2%), Endoscopic Remission (15.6%), Disease Progression (14.1%), and Health-Related Quality of Life (11.9%), represented 57.8% of selections. When considering the top five and top six outcomes, the cumulative proportions were 55.4% and 57.6%, respectively.

Conclusions: This expert-driven Delphi study provides a standardized framework for selecting outcomes in CD RWE studies, improving consistency and comparability across future research in this field.

Background and aims: Inflammatory bowel disease (IBD) often coincides with pregnancy, and disease activity during pregnancy increases the risk of adverse outcomes. We aimed to determine how disease course before conception influences relapse risk during pregnancy, adjusting for established risk factors.

Methods: In this multicenter, retrospective cohort study, we included adult women with IBD who were pregnant during treatment at one of three university hospitals between 2017 and 2022. Using generalized estimating equations, we evaluated associations between relapse during pregnancy and pre-conceptional flares, categorized into three time intervals. Analyses were adjusted for phenotype, disease duration, surgical history, biologic use, smoking, and assisted reproduction. Interaction analyses were conducted with matched non-pregnant women.

Results: We included 386 women (63.4% Crohn's disease, 36.6% ulcerative colitis) with 476 pregnancies. Pre-conceptional flares were significantly associated with relapse if they occurred <3 months [adjusted odds ratio (aOR) 5.289, 95% CI 2.6-10.8, P < .001] or 3-6 months prior to conception (aOR 2.910, 95% CI 1.0-8.2, P = .043), but not 6-12 months prior (aOR 1.636, 95% CI 0.8-3.2, P = .146). Other predictors were not significantly associated with relapse. There was no significant interaction between pregnancy and pre-conceptional disease activity.

Conclusions: This large multicenter study demonstrates that disease activity within 6 months before conception significantly increases the risk of relapse during pregnancy in women with IBD. Our study is the first to assess both the pre-conceptional disease course and a broad set of known risk factors in a real-world cohort.

Background and aims: We assessed placebo rates and associated factors using individual patient data (IDP) from randomized clinical trials (RCTs) in ulcerative colitis (UC).

Methods: We conducted an IPD meta-analysis using Vivli and Yale University Open Data Access data-sharing platforms. Phase 2 and 3 RCTs of advanced biologics in adults with moderate-to-severe UC published since 2010 were included. Pooled placebo rates and 95% CIs were estimated using one- and two-stage meta-analytical approaches. Significant patient-level factors (P < .05) were identified using regression analyses. Primary outcomes were clinical response and remission.

Results: Data were available for 1703 patients from nine studies. For induction trials, overall placebo response and remission rates were 33% (95% CI 29%-38%) and 9% (95% CI 7%-11%). Overall placebo response and remission rates in maintenance trials were 28% (95% CI 18%-41%) and 14% (95% CI 9%-20%). A lower body mass index reduced the odds of placebo response and remission, while higher baseline albumin levels and left-sided (compared to extensive) UC increased the odds of these outcomes. A 1-point increase in the Mayo Clinic Score (MCS) and adapted MCS was associated with a 26% and 27% reduction in odds of clinical remission. For induction trials, prior biologic exposure was associated with lower odds of response and remission. Multicenter trials have lower placebo effects than single-center trials.

Conclusions: These results enable future trials to incorporate design elements that reduce placebo rates as well as a precise benchmark for expected rates in clinical trials that do not include placebo.

Background & aims: The optimal management of inflammatory bowel disease (IBD) patients with a partial response after intravenous (IV) vedolizumab (VDZ) induction remains unclear.

Methods: PRIVEDO was an observational, non-randomized, open-label, prospective cohort study conducted within the Sicilian Network for IBD. It compared subcutaneous (SC) VDZ (108 mg every 2 weeks) versus intensified IV VDZ (300 mg every 4 weeks) in Crohn's disease (CD) or ulcerative colitis (UC) patients with a partial response at Week 14 post-induction. Partial response was defined as: (1) clinical remission with fecal calprotectin >250 µg/g and/or steroid use, or (2) a reduction in the Harvey-Bradshaw Index by ≥3 points (for CD) or in the Partial Mayo Score by ≥2 points (for UC) from baseline, without fulfilling clinical remission criteria. The primary endpoint was steroid-free clinical remission with fecal calprotectin <250 µg/g at Weeks 26 and 52. The secondary endpoints were clinical benefit (remission or partial response), regardless of calprotectin values, and treatment persistence.

Results: 107 patients were enrolled (CD: 58/107, 54.2%; UC: 49/107, 45.8%), allocated to SC (n = 52) or IV (n = 55) groups. The primary endpoint was met more often with SC VDZ at Week 26 (30/52, 57.7% vs. 14/55, 25.5%; P < 0.001; odds ratio [OR]: 3.57, P = 0.004 at multivariable analysis) and at Week 52 (25/52, 48.1% vs. 14/55, 25.5%; P = 0.016; OR: 3.05, P = .029 at multivariable analysis). Clinical benefit was also higher in the SC group at both timepoints, though not statistically significant. Treatment persistence was comparable between the 2 groups (log-rank test, P = .225).

Conclusions: In IBD patients with partial response to IV VDZ induction, switching to SC VDZ may lead to more profound remission than continuing IV optimization.

Background and aims: Colitis-associated cancer (CAC) is the most severe complication of inflammatory bowel disease (IBD). We hypothesized that chronic inflammation activates endogenous anti-inflammatory mechanisms that promote dysplasia by undermining immunosurveillance. Our aim was to determine chronic inflammation-induced immune cell reprogramming in IBD patients at risk for developing CAC.

Methods: This cohort study utilized GeoMx digital spatial profiling and imaging mass cytometry in 11 patients with either CAC or sporadic colorectal cancer (SCRC). Results from this discovery cohort were validated using immunohistochemistry/immunofluorescence in an independent cohort of CAC and SCRC patients (n = 10 and n = 14, respectively), as well as in an independent cohort of IBD patients with (n = 6) and without dysplasia (n = 18).

Results: Histologically uninflamed colon from patients who developed CAC displayed upregulated metabolism and stress response pathways as compared to SCRC patients, indicating ongoing epithelial stress-responses. Endogenous anti-inflammatory mechanisms included increased IL-10 expression by lamina propria IgA+ plasma cells and CD163+ macrophages. T cell recruitment and effector pathways were downregulated in CAC, which was associated with a decrease in CD8+ intraepithelial T cells (IELs) and reduced levels of granzyme B within CD8+ IELs. Decreased CD8+ IEL density was associated with CAC susceptibility, as IBD patients who developed dysplasia showed significantly lower levels of CD8+ IELs than IBD patients who never developed dysplasia.

Conclusions: Chronic inflammation induces endogenous mechanisms to protect from inflammation-induced damage, including increased anti-inflammatory cytokine production and decreased levels of CD8+ IELs. While this may limit inflammation, these mechanisms may also reduce immunosurveillance, favoring the development of CAC.

Background and aims: The submucosa is the most responsive bowel wall layer on intestinal ultrasound (IUS) when assessing treatment response in ulcerative colitis (UC). Submucosal thickening with hyper-echogenicity is observed. This study aimed to quantify echogenicity and understand transmural changes in UC.

Methods: In total, 118 patients were studied in two cohorts. Cohort 1 included colectomy patients: 19 UC patients and 52 controls without inflammatory bowel disease. Cohort 2 included 47 UC patients in a prospective cohort starting anti-inflammatory treatment. In Cohort 1, submucosal inflammation, and fat and collagen deposition were scored by two pathologists using a semi-quantitative scale (0-3). For UC patients in Cohort 1, histopathology and IUS of the sigmoid were location matched. Relative submucosal echogenicity (RSE) was assessed, quantified in grayscale values. In Cohort 2, baseline sigmoid RSE was compared between endoscopic responders (≥1 point decrease in endoscopic Mayo score after 8-26 weeks) and non-responders.

Results: In all colectomized UC patients with preserved wall layer stratification (n = 12, 63%), submucosal fat (score ≥1) was present; in those with loss of stratification (n = 7, 37%), fat was absent (score = 0). RSE was higher when fat was present [95.5 (IQR 86.5-116.9) vs 8.1 (IQR 5.8-23.0) grayscale values, P < .001], with no significant differences for inflammation and collagen. In Cohort 2, RSE was higher in non-responders (n = 17) compared to responders (137.1 ± 50.9 vs 88.3 ± 49.6 grayscale values, P = .003). An RSE of >108 grayscale values predicted non-response [OR: 0.07 (95% CI: 0.01-0.44), P = .004].

Conclusion: Submucosal hyper-echogenicity on IUS indicates fat deposition and predicts non-response in UC.