Journal of Crohn's & colitis最新文献

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.

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.

Background: Prior studies showed worse outcomes in obese inflammatory bowel disease (IBD) patients, especially those related to hospitalizations, surgery, and steroid-free remission. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated significant metabolic benefits for patients with type 2 diabetes mellitus (T2DM) and obesity. Hence, GLP1-RAs may improve clinical outcomes in patients with IBD, especially those with obesity. The objective was to systematically evaluate the impact of GLP1-RAs on clinical outcomes in patients with IBD.

Methods: A comprehensive literature search was performed using the databases PubMed, Embase, Web of Science, and Cochrane Library from inception to March 15, 2025. Studies reporting outcomes related to GLP1-RAs in patients with IBD were included. Primary outcomes included weight loss and various IBD-related co-endpoints such as hospitalizations, surgery, corticosteroid use, and advanced therapy initiation.

Findings: In total, 11 studies with 16 242 patients with IBD treated with GLP1-RAs were included. Weight loss was achieved using semaglutide (-9.6 kg, 95% confidence interval [CI]: -12.0; -7.2), liraglutide (-9.4 kg, 95% CI: -13.0; -5.8), and tirzepatide (-11.8 kg, 95% CI: -18.3; -5.4) after 3 months of follow-up. In meta-analyses, GLP1-RAs were associated with lower risk of surgery for effect sizes (logHR: 0.61 [95% CI: 0.44-0.84], I 2 = 0%) and event frequencies (odds ratio [OR]: 0.46 [95% CI: 0.32-0.67], I 2 = 42%). Sensitivity analysis for body mass index (BMI) showed a lower risk of hospitalizations and surgery in patients with obesity (BMI ≥ 30).

Interpretation: Patients with IBD and obesity using GLP1-RAs were able to achieve significant weight loss and had lower risks of surgery and hospitalizations. Our findings require confirmation in prospective trials of GLP1-RAs in IBD.

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.