Journal of Crohn's & colitis最新文献

Background and aims: Symptoms of anxiety and depression are common in inflammatory bowel disease (IBD); the aim of this study was to assess the proportion of anxiety and depression in patients newly diagnosed with IBD, compare the rates with the Norwegian general population (NGP), and examine associations with selected sociodemographic, psychological, and disease-related factors.

Methods: This prospective cohort study included newly diagnosed patients with IBD, and data from the HUNT4 survey of the NGP. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Crude statistical comparisons were performed using t-tests, Mann-Whitney U test, chi-square tests, or Fisher's exact tests. Adjusted associations were modeled using multiple robust linear regression and multiple logistic regression.

Results: In total, 938/1562 (62.1%) patients with IBD completed the Hospital Anxiety and Depression Scale (Crohn's disease [CD]: n = 297, ulcerative colitis [UC]: n = 641). The proportion of anxiety was 37.4% in CD and 32.1% in UC, while depression was reported by 21.9% and 16.8%, respectively. Both rates were significantly higher than those observed in the NGP (17.5% for anxiety and 9.4% for depression). Compared with the NGP, males with CD had significantly higher levels of anxiety and depression, males with UC had elevated anxiety only, while females with CD and UC showed increased anxiety and depression. Both substantial fatigue and general self-efficacy were significantly associated with anxiety and depression in IBD.

Conclusions: Newly diagnosed patients with IBD experienced significant psychological challenges compared with the NGP. Early identification of anxiety and depression may enable targeted interventions.

Background: Patient knowledge is pivotal to inflammatory bowel disease (IBD) management, yet educational opportunities vary widely worldwide. This scoping review maps existing evidence on patient knowledge, explores regional and demographic differences, and identifies gaps to guide culturally adaptable interventions.

Methods: Following PRISMA-ScR guidelines, PubMed and Embase were searched up to December 31, 2025, for studies assessing patient knowledge in IBD. Eligible adult and pediatric studies were independently screened and synthesized by two reviewers across key knowledge domains, including disease basics, treatment, complications, colorectal cancer (CRC) risk, surgery, vaccination, and diet.

Results: From 8464 records, 53 studies met inclusion criteria. Validated tools, including CCKNOW and IBD-KNOW, predominated in adult studies, whereas IBD-KID and IBD-KID2 were used in pediatric populations. Knowledge levels varied widely: correct understanding of anatomy (36%-68%), risk factors (16%-85%), CRC risk (24%-78%), and surgery (13%-16%) was frequently suboptimal. Only 5%-51% recognized azathioprine as an immunosuppressant. Awareness of vaccination (39%-78%) and dietary relevance (23%-65%) remained limited. Gastroenterologists were the primary information source (42%-96%). Higher knowledge was associated with both sociodemographic factors (female sex, younger age, higher educational attainment) and disease-related characteristics (longer disease duration, prior exposure to biologics or surgery, Crohn's disease phenotype). Patients in Europe and North America had higher awareness than those in Asia and the Middle East, probably due to better healthcare access and patient education infrastructure.

Conclusions: Global IBD knowledge and awareness remain inadequate and uneven across regions and domains. Updated, culturally appropriate and adaptable assessment tools and multidisciplinary, technology-enabled educational strategies are needed to enhance IBD literacy.

Background: UNITI Jr is a phase 3 study evaluating the efficacy, safety, and pharmacokinetics of ustekinumab, an interleukin-12/-23 antagonist, in pediatric patients with moderately to severely active Crohn's disease. Results from patients weighing at least 40 kg are reported.

Methods: Patients at least 40 kg and aged less than 18 years with a Pediatric Crohn's Disease Activity Index score of >30 received a single intravenous weight-tiered induction dose of ustekinumab. After 8 weeks, patients were randomized to subcutaneous ustekinumab 90 mg every 8 or 12 weeks. The primary endpoint was clinical remission at Week 8. Secondary endpoints included clinical response (Weeks 8, 52), endoscopic response (Weeks 16, 52), clinical remission, and corticosteroid-free remission (Week 52).

Results: Of 48 patients, median age was 15.0 years (interquartile range: 14.0-16.0). At Week 8, 52.1% (25/48) achieved clinical remission and 93.8% (45/48) achieved clinical response. At Week 16, 29.8% (14/47) achieved endoscopic response. Clinical remission at Week 52 was achieved in 15/25 (60.0%; every 12 weeks) and 10/23 (43.5%; every 8 weeks). Three patients (6.3%) discontinued ustekinumab between Weeks 8 and 52. Ustekinumab was safe and well-tolerated; adverse event rates were similar between groups. Immunogenicity was low; trough median (mean) steady-state serum ustekinumab concentrations following 8 weeks of dosing were 1.38 (2.08) to 1.74 (2.32) μg/mL and were comparable to levels in adult patients: 2.83 (2.05) μg/mL.

Conclusions: Ustekinumab induction and maintenance therapy was effective and safe through 52 weeks in pediatric patients weighing at least 40 kg with moderately to severely active Crohn's disease.

Trial registration numbers: NCT04673357.

Background and aims: Local therapies involving direct delivery of agents to fistula tracts in perianal fistulizing Crohn's disease (PFCD) have been explored but are not standard in clinical practice. We aimed to conduct a systematic review of local therapies for PFCD to evaluate their role in fistula closure, considering current pathophysiological insights and contemporary surgical and medical expertise.

Methods: We performed a systematic review assessing the efficacy of local therapies for PFCD, excluding mesenchymal stem cell therapies, which have been reviewed elsewhere. The reporting quality of the studies was assessed using a validated checklist.

Results: The systematic review included 31 studies evaluating fibrin glue (n = 11), fistula plugs (n = 11), locally injected medications (n = 5), ointments (n = 3), and platelet-rich plasma (n = 2). Fibrin glue showed short-term success (healing rates 30%-91%) but poor long-term outcomes (26%-57%). Fistula plugs had variable success rates (15%-85%) with minimal benefit from repeated applications. Locally injected biologics achieved healing rates of over 60%, often with durable responses. Metronidazole ointment had only short-term efficacy, while tacrolimus had no significant benefit. A potential approach to improving the efficacy and durability of local therapies for PFCD may involve surgical preconditioning (through curettage and internal orifice closure) and the efficient delivery of agents into fistula tracts that modulate microbial communities, inflammation, and, ultimately, wound healing.

Conclusions: There is an unmet need to generate novel local therapies that achieve long-lasting fistula closure. To facilitate their development, the delineation of host and microbial pathways contributing to PFCD pathogenesis and research in drug delivery systems are needed.

Background and aims: Hepcidin, the master regulator of systemic iron metabolism, is influenced by iron availability and inflammation. In inflammatory bowel disease (IBD), the interplay between iron deficiency and inflammatory activity remains incompletely understood. This study aimed to characterize hepcidin regulation in ulcerative colitis (UC) and Crohn's disease (CD) in relation to iron status and inflammatory markers.

Methods: In this cross-sectional multicenter study, 589 individuals were enrolled: 178 controls, and 130 UC and 281 CD patients. Patients were stratified by iron status and disease activity. Serum hepcidin, iron parameters, and inflammatory and clinical data were collected. Iron deficiency was defined using the ECCO criteria and a combined ferritin and transferrin saturation definition. Group comparisons, correlations, and multivariable linear regressions were performed.

Results: Hepcidin correlated positively with C-reactive protein in CD (r = .125; P = .038) and negatively with fecal calprotectin in UC (r = -.311; P < .001). Using the ECCO definition, hepcidin levels in CD were higher than in controls within comparable iron-status categories (iron deficiency: 4.359 [IQR 2.094-8.906] ng/mL vs 2.300 [IQR 1.375-4.950] ng/mL, P = .019; normal iron stores: 10.402 [IQR 6.398-17.683] ng/mLvs 8.500 [IQR 5.300-12.150] ng/mL, P = .023). In UC, no significant differences from controls were observed, under the same criteria. In correlation analyses, ferritin showed the strongest association with hepcidin across groups (P < .001).

Conclusions: Ferritin showed the strongest association with hepcidin across IBD, but regulation differed by disease. In UC, lower hepcidin levels were associated with intestinal inflammatory activity measured by fecal calprotectin, whereas in CD, higher hepcidin levels were associated with systemic inflammation despite iron deficiency. These findings highlight hepcidin's potential as a biomarker linking iron status and inflammatory type in IBD.

Background and aims: While colonoscopy with mucosal biopsies remains the gold standard for evaluation and surveillance of Crohn's disease (CD), it does not allow a full evaluation of inflammation status over the entire small bowel. This study aims to evaluate the efficacy of host transcriptomics of fecal aspirates in assessing small bowel inflammation in asymptomatic CD patients.

Methods: Biopsies and fecal aspirate samples were prospectively obtained from CD patients in clinical remission undergoing same-day colonoscopy and video-capsule endoscopy (VCE). Host transcriptomics analysis was performed, and findings were associated with clinical, laboratory, and endoscopic parameters, and validated using a 2-gene-based qRT-PCR assay.

Results: Our cohort comprised 56 asymptomatic Crohn's patients and 16 healthy controls. Thirty-five asymptomatic patients (62.5%) demonstrated active inflammation by colonoscopy or VCE. Transcriptomic analysis of fecal aspirates distinguished inflamed from noninflamed patients, revealing substantially more differentially expressed genes than biopsies (2352 vs 22, respectively). Inflamed aspirates showed enrichment of natural killer and regulatory T cells, along with activation of immune pathways. We devised a 10-gene predictive model for endoscopic inflammation in asymptomatic Crohn's patients with superior discrimination compared to stool calprotectin (AUC = 0.82 vs 0.58) and closely approximates the accuracy of VCE (AUC = 0.90). An additional 10-gene diagnostic model differentiated CD patients from healthy controls (AUC = 0.952). Both models were validated using qRT-PCR as well as an additional validation cohort.

Conclusion: Transcriptomic profiling of rectal fecal aspirates reliably detects small bowel inflammation and identifies specific immune pathways in asymptomatic CD. The resulting models offer potential biomarkers for CD diagnosis and monitoring.

Background & aims: The expanding use of advanced IBD therapies creates an urgent need for pregnancy safety data. While anti-TNF safety is well-established, evidence for newer agents (vedolizumab, ustekinumab, and JAK inhibitors) remains limited. We aimed to quantify adverse pregnancy outcomes among women exposed to advanced therapies.

Methods: Random-effects models were used to calculate pooled prevalence estimates, with subgroup analyzes by therapeutic class. Restricted cubic spline meta-regression evaluated maternal age, disease activity, disease duration, phenotype, and third-trimester exposure as moderators.

Results: 67 observational studies with 17 441 pregnancies were included. Overall pooled prevalence rates were 8.2% (95% CI, 6.2-10.8) for early pregnancy loss, 8.9% (95% CI, 7.9-10.0) for preterm birth, 0.3% (95% CI, 0.2-0.6) for stillbirth, 6.6% (95% CI, 5.5-7.8) for low birth weight, 2.9% (95% CI, 2.2-3.9) for congenital malformations. JAK inhibitors and ustekinumab exposures were associated with higher pooled prevalence estimates of early pregnancy loss, while vedolizumab exposure was associated with higher estimates of preterm birth. Meta-regression identified disease duration, third-trimester exposure, maternal age, active disease, and Crohn's disease proportion as significant moderators of selected outcomes.

Conclusion: Advanced IBD therapies demonstrate an overall favorable safety profile. Active disease, older maternal age, and longer disease duration were significant predictors of complications. Associations with third-trimester exposure do not support routine discontinuation, as this likely reflects underlying disease severity rather than treatment effect, reinforcing the priority of maintaining remission during pregnancy.

Background and aims: Chronic background mucosal inflammation contributes to colorectal cancer (CRC) development in ulcerative colitis (UC), but its prognostic impact is unclear. We evaluated whether background mucosal inflammation documented at cancer diagnosis is associated with oncologic outcomes.

Methods: This retrospective study analyzed 1189 UC patients diagnosed with CRC using a nationwide, multicenter database in Japan. Patients were classified as CRC within the UC-involved area (within-area) or outside the UC-involved area (outside-area), based on tumor location relative to the UC disease extent documented endoscopically at cancer diagnosis. The primary end point was 5-year recurrence-free survival (RFS), and the secondary end point was 5-year cancer-specific survival (CSS). In within-area cases, inflammation severity was assessed using the Mayo Endoscopic Score (MES), stratified as Inactive, Mild-Moderate, and Severe.

Results: Of the 723 eligible patients, 683 had within-area and 40 outside-area CRC. Five-year RFS was significantly lower in within-area than outside-area CRCs (75.1% vs 87.6%, P = 0.022). Multivariable Cox regression analysis of RFS revealed this classification as an independent prognostic factor (hazard ratio = 2.99, 95% confidence interval: 1.09-8.18, P = 0.030). A significant difference was also observed in 5-year CSS (P = 0.038). Among within-area cases, higher MES was associated with stepwise declines in RFS (P = 0.150), and a similar, statistically significant gradient in CSS (P = 0.048).

Conclusions: Background mucosal inflammation at cancer diagnosis is associated with significantly worse prognosis of CRC in UC patients. Systematic endoscopic assessment at cancer diagnosis may aid prognostic stratification and inform management.