Journal of Crohn's & colitis最新文献

Background: External validation of predictors of anti-tumor necrosis factor (TNF) outcomes remains limited, particularly in children. We conducted a systematic review of the literature to identify predictors of therapeutic success and validated them in a prospective pediatric cohort.

Methods: We searched PubMed and Embase for studies reporting clinical and laboratory predictors of anti-TNF outcomes in Crohn's disease (CD). Identified predictors were evaluated in a prospective cohort of 186 children with CD initiating anti-TNF. Univariable logistic regression assessed individual predictors, and previously published multivariable models were validated using the area under the curve (AUC).

Results: Of the 4840 studies screened, 42 were included; seven (17%) focused on children and only four were rated as low risk of bias. We identified 24 individual predictors and five multi-item models. Of these, prior corticosteroid use (odds ratio [OR], 2.84, 95% CI, 1.12-7.15) and immunomodulator combination therapy (OR 6.36, 95% CI, 2.39-17.10) were associated with increased risk of primary non-response. Disease activity at 4 months, reflected by C-reactive protein and disease activity indices, predicted remission at 12 months. Loss of response was associated with elevated inflammatory markers at 4 months and with partial clinical response. The five multivariable models demonstrated varying performance in children (AUC 0.54-0.76).

Conclusion: Only a few of the variables suggested to predict response to anti-TNF showed acceptable performance in pediatric CD, mainly those that included post-induction indicators. These findings highlight the limited generalizability of existing predictors and the importance of external validation before clinical implementation of prediction rules.

Background and aims: Not all patients, as with other inflammatory bowel disease (IBD) treatments, respond to modulation of kinase activity. To improve the precision of therapeutic interventions, a better understanding of the mucosal inflammatory environment is essential. This study investigates mucosal kinase activity and cytokine/chemokine profiles in IBD and in relation to tofacitinib response.

Methods: Paired inflamed and non-inflamed colonic biopsies were collected from patients with Crohn's disease (CD, n = 16), ulcerative colitis (UC, n = 16), and non-IBD controls (n = 4) to assess IBD-associated kinase activity and cytokine/chemokine profiles. Additionally, colonic samples were collected from UC patients before the start of tofacitinib treatment (cohort 1, n = 12) and both before and after 8 weeks of treatment (cohort 2, n = 16), to assess tofacitinib response-related kinase activity profiles.

Results: The kinase activity profiles exhibited significant differences between inflamed and non-inflamed mucosa, with more pronounced alterations observed in UC compared to CD. The increase in kinase activity was most pronounced in the tyrosine kinase families. Responders to tofacitinib demonstrated higher baseline mucosal kinase activity, although only two predicted kinases (DCLK1 and ATR) were consistently identified. In responders, mucosal kinase activity significantly decreased after 8 weeks of treatment.

Conclusion: Mucosal kinase activity profiles are associated with inflammation in IBD, with distinct differences between UC and CD. Baseline kinase activity appears to predict response to tofacitinib, with a marked reduction in kinase activity observed after 8 weeks of treatment in responders. These findings highlight the potential of kinase activity profiling in optimizing therapeutic strategies for IBD.

Background and aims: Most patients with Crohn's disease (CD) who have undergone ileocolonic resection experience recurrent inflammation within 1 year after surgery. We examined the molecular basis underlying gastrointestinal inflammation in postoperative CD across 3 common anatomic locations of recurrence.

Methods: To characterize spatial transcriptomic signatures, this study utilized biopsies from the colon, neo-terminal ileum, and anastomosis of patients with postoperative CD in the PREDICT-OR study. Sample analyses were performed with 10X Genomics Visium CytAssist system V2.0, and data analyses with R.

Results: Histologically inflamed biopsies from all locations shared transcriptional signatures across 3 cellular niches (myeloid, B, T cells) and a specialized epithelial cell type expressing inflammation-associated genes. Differentially expressed genes overexpressed inflammatory pathway activity across the 3 locations, whereas hypoxic pathways were less apparent. In addition to genes for known treatment targets, epidermal growth factor receptor and mitogen-activated protein kinase pathways were upregulated. Cellular niches shaped inflammatory microenvironments through endoplasmic reticulum stress and extracellular matrix remodeling signaling.

Conclusions: Application of spatial transcriptomics revealed a common disease signature for postoperative CD across the colon, neo-terminal ileum, and anastomosis. Inflamed biopsies from all locations demonstrated similar immune cell and inflammatory gene expression patterns as opposed to hypoxic pathways, and unique inflammatory pathways were revealed.

Background and aims: Crohn's disease (CD) is a chronic, immune-mediated inflammatory disorder. Its pathophysiology involves dysregulation of both innate and adaptive immune responses, which can occur in clonal hematopoiesis of indeterminate potential (CHIP) individuals. Therefore, we hypothesize that CHIP may influence CD incidence. However, no study has explored the association between CHIP and incident CD. We analyzed UK Biobank data to investigate the association between CHIP and incident CD.

Methods: CHIP was defined based on whole-exome sequencing data. The outcome was incident CD. Cox regression models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for CD in relation to CHIP.

Results: This study included 461 913 participants, of whom 14 339 (3.1%) had CHIP. The incidence rate of CD was 21.6 and 37.7 per 100 000 person-years for individuals without and with CHIP, respectively. We found a statistically significant increased risk of CD among individuals with CHIP (HR, 1.68; 95% CI, 1.30-2.16), compared with the reference group. This association was particularly stronger in individuals with JAK2-mutant CHIP (HR, 7.28; 95% CI, 1.82-29.13), ASXL1-mutant CHIP (HR, 3.07; 95% CI, 1.74-5.44), and DNMT3A-mutant CHIP (HR, 1.73; 95% CI, 1.24-2.42). Additionally, the association did not vary greatly by demographic, socioeconomic, lifestyle factors, CHIP clone size, or cancer comorbidity.

Conclusions: CHIP was associated with a markedly increased risk of subsequent CD. The association was particularly stronger in JAK2-mutant CHIP, ASXL1-mutant CHIP, and DNMT3A-mutant CHIP. The findings of this study may offer potential insights for future investigations into the mechanistic underpinnings of CD.

Importance: Resistant ulcerative proctitis (UP) represents a clinical conundrum, often necessitating the use of systemic therapy despite the disease being localized. Fecal microbiota transplantation (FMT) has proven efficacy for inducing remission in ulcerative colitis (UC) but has not been evaluated in UP.

Objectives: To assess the safety and efficacy of FMT enema therapy for resistant UP.

Design: Single-arm open-label pilot study.

Setting: The Queen Elizabeth Hospital, Adelaide, Australia.

Participants: Thirty patients with active UP or distal UC (total Mayo 3-10 with endoscopic Mayo subscore ≥1), with maximal disease extent up to ≤3030 cm from anal verge).

Interventions: Vancomycin conditioning and dietary education, followed by six anaerobically prepared single-donor FMT retention enemas administered over 8 weeks.

Main outcomes and measures: The primary end point was safety and tolerability of FMT therapy. Secondary endpoints included combined clinical and endoscopic remission (Mayo Clinic score ≤2 with endoscopic subscore ≤1), histological remission, patient-reported outcomes, and exploratory microbial analysis.

Results: Thirty participants were enrolled (median age 41 years; 17 [57%] female). Serious adverse events occurred in 3 patients, including flare of UC (n = 2) and Clostridioides difficile colitis (n = 1). Eighteen patients (60%) reported mild-moderate adverse events, most commonly gastrointestinal symptoms. Combined clinical and endoscopic remission was achieved in 10 patients (33.3%). Higher baseline Mayo score (odds ratio [OR]: 0.28, P = .008) and fecal calprotectin (OR: 0.66, P = .049) predicted failure to achieve remission. Participants demonstrated a decrease in Shannon diversity (P = .02) following the dual intervention of vancomycin conditioning and FMT.

Conclusions and relevance: Antibiotic conditioning followed by FMT enema therapy was well tolerated and demonstrated efficacy in inducing clinical remission in UP. Further controlled studies of FMT in UP are warranted alongside a mechanistic assessment of both fecal and mucosa-associated microbiome.

Background and aims: Seven new advanced therapies, belonging to three new classes, have been approved for the treatment of inflammatory bowel diseases (IBD) since 2021. We examined trends in utilization of advanced therapies in the USA since 2021.

Methods: Using de-identified electronic health record data from 71 US health systems, we examined quarterly trends in utilization of different advanced therapies in patients with ulcerative colitis and Crohn's disease between 2021 and 2025, using interrupted time-series analysis utilizing Prais-Winsten regression.

Results: In 11 093 patients with ulcerative colitis treated with advanced therapies, we observed an increase in use of upadacitinib (12.1% in Q2/2025; P < .001, compared with first quarter of prescription), interleukin-23p19 (IL23p19) antagonists (5.5%; P = .03), and ustekinumab (9.5%; P = .04), decline in use of tumor necrosis factor (TNF) antagonists (34.5%; P = .003), and stable use of vedolizumab (33.6%; P = .17) and sphingosine-1 phosphate receptor modulators (1.6%; P = .28). In 15 951 patients with Crohn's disease treated with advanced therapies, we observed an increase in use of IL23p19 antagonists (15.0% in Q1/2025; P = .003) and upadacitinib (5.9%; P < .001) and decline in use of TNF antagonists (50.2%; P = .001) and ustekinumab (13.5%; P < .001).

Conclusions: Contemporary trends in advanced therapy utilization in patients with IBD suggest an increased utilization of upadacitinib and anti-interleukins, accompanied by a decline in use of TNF antagonists in the USA.

Background and aims: Evidence from rheumatology supports a within-class treatment switch for JAK-inhibitors (JAKi), but data in ulcerative colitis (UC) remain limited. We aimed to assess the effectiveness and safety of initiating a second JAKi in patients with UC previously treated with another JAKi.

Methods: We conducted a multicentre retrospective study, including patients with UC starting a second JAKi after prior JAKi exposure. The primary endpoint was week 12 steroid-free clinical remission (SFCR-rectal bleeding subscore = 0, stool frequency subscore ≤ 1, and no steroids).

Results: We included 243 patients [median follow-up: 38 (21-57) weeks]. At weeks 12, 26, and 52, SFCR was achieved in 116/243 (48%), 120/243 (49%), and 69/243 (28%), respectively. Secondary loss of response to the first JAKi was associated with higher SFCR at week 12 compared to primary failure (OR = 1.92, 95%CI = 1.11-3.30, p = 0.02). Higher baseline disease activity (OR = 0.68, 95%CI = 0.68-0.55, p < 0.01) and steroid use (OR = 0.23, 95%CI = 0.13-0.42, p < 0.01) had lower odds of week 12 SFCR. Endoscopic remission occurred in 22/243 (9%) (

Conclusion: Treatment with a second JAKi is effective and safe in patients with UC already exposed to JAKi. Primary failure to a first JAKi and steroid use at initiation of the second JAKi might reduce the likelihood of success with the second JAKi.

Background and aims: The outcome of Crohn's Disease (CD) patients with entero-enteric anastomosis (EEA) after small bowel resection is undefined. The primary aim of the present case-control study was to compare the clinical recurrence rate within the first 5 years after surgery in CD patients with small bowel EEA (Cases) versus age-matched patients with ileo-colonic anastomosis (ICA, Controls).

Methods: All CD patients with EEA were matched for age at diagnosis (±5 years) and smoking habits with two Controls with ICA. Inclusion criteria were: (1) age ≥18 years; (2) EEA or ICA for CD; (3) ≥5 years of follow-up after surgery. Exclusion criteria were: (1) missing data; (2) ostomy; (3) stricturoplasty.

Results: The study population included 51 CD patients with EEA and 102 matched Controls with ICA. During the first 5 years after surgery, clinical recurrence and CD-related hospitalizations were more frequent in Cases (34 [66.7%] vs 43 [42.2%], P = .007; 25 [49%] vs 23 [22.5%], P = .001). During the same period, use of corticosteroids, immunosuppressors, and biologics were also more frequent in Cases (26 [50.9%] vs 18 [17.6%], P < .0001; 21 [41.2%] vs 24 [23.5%], P = .03; 23 [45.1%] vs 15 [14.7%], P = .03). Survival time from clinical recurrence and hospitalization were shorter in Cases (2.36 [1.29-4.35], P = .003; 1.71 [1.06-2.77], P = 0.02). EEA and use of immunosuppressors before surgery were risk factors for clinical recurrence and CD-related hospitalization at 5 years (2.68 [1.11-6.45], P = .02; 2.61 [1.21-5.6], P = .01; 2.53 [1.05-6.09], P = .03; 2.44 [1.18-5], P = .01).

Conclusions: The clinical outcome is more severe in CD patients with EEA than in those with ICA, being associated with a higher rate of clinical recurrence and hospitalization after surgery.

Background: Type 2 diabetes mellitus (T2DM) may adversely affect the course and treatment outcomes of Crohn's disease (CD). However, data remain inconsistent.

Aims: To evaluate the impact of T2DM on clinical outcomes and advanced therapy use in patients with CD using real-world electronic health record data.

Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adult patients with CD were stratified by the presence of T2DM. Propensity score matching was used to balance demographic and clinical characteristics. Primary outcomes included corticosteroid use, abdominal surgery, drug-related adverse events, and the initiation of advanced therapies. Secondary outcomes included the incidence of neoplasms and mental disorders. Time-to-event outcomes were analyzed using Kaplan-Meier curves and hazard ratios.

Results: After matching, 7182 patients were included in each cohort. Corticosteroid use was higher in diabetic patients (61.6% vs 55.2%; P < .001), as were abdominal surgery (32.8% vs 31.1%; P = .010) and drug-related adverse events (4.3% vs 2.4%; P < .001). Use of anti-TNF (10.4% vs 12.2%; P < .001) and IL-23 inhibitors (4.6% vs 5.4%; P = .018) was lower in diabetic patients. Use of vedolizumab (2.4% vs 2.6%; P = .401) and JAK inhibitors (0.6% in both; P = .955) was similar. Neoplasm rates were comparable (3.5% vs 3.2%; P = .386), while mental disorders were more common in the diabetic cohort (51.5% vs 41.2%; P < .001).

Conclusions: Patients with CD and coexisting T2DM experience a more severe disease course yet appear to be undertreated with advanced therapies. These findings highlight the need for tailored, multidisciplinary management strategies in this high-risk population.