Inflammatory Bowel Diseases最新文献

Introduction: Real-world data regarding subcutaneous infliximab (SC-IFX) in patients with pediatric inflammatory bowel disease IBD (PIBD) is scarce. We evaluated SC-IFX as maintenance therapy in PIBD patients who switched to SC-IFX from intravenous infliximab (IV-IFX) treatment.

Methods: In this retrospective multicenter study we identified PIBD patients who switched to SC-IFX. The primary outcome was treatment persistence at up to 12 months post-switch. Secondary outcomes included relapse rate (defined as Pediatric Ulcerative Colitis Activity Index [PUCAI]  ≥10/ weighted PCDAI  ≥ 12.5 with biochemical/endoscopic evidence of disease activity), IFX trough levels, immunogenicity, safety, and acceptance.

Results: Sixty-six patients switched to SC-IFX (48% males; median switch-age, 16.5 years; IQR, 14.9-17.3 years; median switch-weight, 60 kg; range, 13-102 kg), 41/66 (62%) with Crohn Disease. Pre-switch, the median IV-IFX maintenance dose was 10 mg/kg every 6 weeks; 58/66 patients (88%) were in clinical remission. The initial SC-IFX regimen was 120 mg every other week in 62/66 patients (94%). SC-IFX persistence was 78% (95% CI, 66-91) at 12 months post-switch, with 89% of patients persisting on IFX, either intravenous (IV) or subcutaneous (SC), at the end of follow-up. Relapses were observed in 11/66 patients (17%) over a median follow-up of 11.0 months (IQR, 5.1-12.0); 6 patients underwent SC-IFX dose intensification, with 3 successfully regaining clinical response. Regarding anti-drug antibodies (ADA), 3 out of 4 patients who were ADA positive on IV-IFX resolved post-switch. Overall, 19/66 patients (29%) reported 21 adverse events (AEs), including 3/21 severe AEs. The majority (53/66 patients; 80%) expressed a positive attitude toward SC-IFX.

Conclusions: The largest documented PIBD cohort switching to SC-IFX to date showed high treatment persistence at 1 year, confirming SC-IFX as an effective and safe maintenance alternative to IV-IFX.

Background: Some patients with ulcerative colitis (UC) develop advanced liver disease due to conditions such as primary sclerosing cholangitis (PSC) and may require liver transplantation (LT). However, data on the long-term course of UC and the use of advanced therapies in LT recipients are limited. We aimed to evaluate UC activity before and after LT, as well as the role of advanced therapies over extended follow-up in this population.

Methods: This was a retrospective, multicenter cohort study including 213 patients with UC who underwent LT between 2000 and 2022. Clinical disease activity (partial Mayo score), endoscopic disease activity (Mayo endoscopic subscore), and the use of advanced therapies were evaluated before and after transplantation.

Results: Among the 213 patients, the clinical remission rate was 84.7% before and 81.2% after LT, showing no significant change (P = .416). Despite stable clinical remission, 27.9% of patients exhibited moderate-to-severe endoscopic inflammation during long-term follow-up (mean: 110 months). The use of advanced therapies increased significantly after LT (from 3.7% to 12.7%, P = .005) and was not associated with an increase in infectious complications (P = .591).

Conclusions: In most patients, clinical disease activity remains stable after LT. However, persistent moderate-to-severe mucosal inflammation is observed in a substantial subset during long-term follow-up. Advanced therapies, particularly vedolizumab, are being used more frequently in this setting and may offer disease control without a corresponding increase in infection risk. These findings underscore the need for individualized, interdisciplinary management and further prospective evaluation of treatment strategies in this population.

Background: The inflammatory bowel disease (IBD) ulcerative colitis (UC) is characterized by colonic mucosal inflammation and barrier dysfunction. We hypothesized that UC causes persistent defects in mucosal homeostasis, evident even in the absence of active inflammation, contributing to disease chronicity.

Methods: To test our hypothesis, we grew patient biopsy-derived sigmoid colonoids into air-liquid interface (ALI) monolayers, characterizing them through microscopy, proteomics, bulk RNA Sequencing (RNAseq), and their susceptibility to UC patient-isolated Escherichia coli pathobiont p19A.

Results: Non-IBD ALI monolayers formed uniform crypt-like structures and a thick mucus layer containing all epithelial-derived proteins previously identified in human colonic mucus. In contrast, ALI monolayers from UC patients displayed a range of impairments, with classification ranging from a mild phenotype with distorted architecture and a thinner, more permeable mucus layer to a severe phenotype with defects in cellular differentiation and an inability to produce a mucus layer. With the use of transcriptome analysis, we identified activated pathways associated with extracellular matrix formation and cell signaling, including numerous cancer-associated genes in UC ALI monolayers, which also proved significantly more susceptible to E. coli p19A.

Conclusions: Taken together, the culturing of patient biopsies into ALI colonoid monolayers provides a powerful model to assess human colonic mucosal development, healing, homeostasis, and mucus barrier function, revealing that UC-derived colonoid monolayers display a range of developmental and functional defects that persist in the absence of inflammation.

Background: Autologous hematopoietic stem cell transplantation (aHSCT) holds promise as a therapeutic strategy in patients with severe chronic inflammatory conditions that are refractory to conventional treatment, including Crohn's disease. The success of aHSCT is thought to be grounded in resetting the break in immunological tolerance, but the exact mechanisms underlying its effects remain incompletely understood.

Methods: We followed the immune reconstitution of nine patients with severe refractory Crohn's disease before and after aHSCT, ranging from 1 month until 2 + years follow-up. We used flow cytometry on peripheral blood mononuclear cells and intestinal biopsy samples, as well as Olink on plasma samples.

Results: In line with previous research, we observed a strong change in the peripheral T cell subset composition from 1 month after transplantation, with a reversal of the CD4+/CD8+ ratio and a reduction of naïve over effector memory T cells (T-EM). Non-responders appeared distinct by retaining a higher CD4+/CD8+ ratio and higher naïve over T-EM frequencies. These differences could already be discerned at baseline, before transplantation. Functionally, we observed only minimal changes in the peripheral T cell profile related to inflammation and homing, but a small increase in regulatory markers. Remarkably, the local intestinal T cell composition did not mirror changes in the periphery, with an increased CD4+/CD8+ ratio in intestinal biopsies post-aHSCT.

Conclusions: Autologous hematopoietic stem cell transplantation had pronounced effects on the peripheral T cell composition, especially in responders. Changes in T cell subset composition were more pronounced than changes in the functional T cell profile.

Background and aims: The characteristics and incidence of esophagogastroduodenal involvement in Crohn disease remain unclear in Korea. In this study we aimed to investigate the prevalence and clinicopathological characteristics of Crohn disease with esophagogastroduodenal involvement.

Methods: A total of 115 patients with Crohn disease who underwent esophagogastroduodenoscopy (EGD) with esophageal, gastric, and duodenal biopsies were prospectively enrolled in 2020-2021 at a tertiary care center. Five specimens were obtained-1 each from the esophagus, gastric body, gastric antrum, duodenal bulb, and second duodenal portion-and histologically reviewed.

Results: The median patient age was 30.0 years, and 74.8% of patients were male. Based on histological features, 56 patients (48.7%) had esophagogastroduodenal involvement (15 esophageal, 44 gastric, 36 duodenal). Notable histopathological findings included non-caseating granulomas in 8 cases (7.0%), focally enhanced gastritis in 38 cases (33.0%), and lymphocytic esophagitis in 13 cases (10.7%). Endoscopic findings suggestive of esophagogastroduodenal involvement were detected in 94 of 115 patients (81.7%). Typical findings included longitudinal or aphthous erosions (esophagus, 3/115 [2.6%]; stomach, 45/115 [39.1%]; duodenum, 19/115 [16.5%]), longitudinal or aphthous ulcers [duodenum: 4/115 (3.5%)], bamboo-joint-like appearance [stomach: 81/115 (70.4%); duodenum: 3/115 (2.6%)], and scar changes [stomach: 2/115 (1.6%); duodenum: 3/115 (2.6%)]. In multivariable analysis, elevated fecal calprotectin (≥100 μg/g) was associated with esophagogastroduodenal involvement in Crohn disease (odds ratio, 6.57; 95% CI, 1.99-21.66; P <.001).

Conclusions: The proportion of esophagogastroduodenal involvement was relatively high among Korean patients with Crohn disease who underwent EGD. In patients with elevated fecal calprotectin, EGD with histopathological examination is recommended to identify esophagogastroduodenal involvement.

Background: Despite the common use of opioids in patients with inflammatory bowel disease (IBD), there are limited studies on the prevalence of chronic opioid use in this population.

Methods: We conducted a nationwide Danish register-based study to examine the prevalence proportion of chronic opioid use in patients with IBD from 1996 to 2021. Analysis was performed for patients with Crohn's disease (CD) and ulcerative colitis (UC) and stratified by sex and age groups of young adults (18-39 years), adults (40-59 years), and elderly (+60 years).

Results: A total of 51 837 patients with IBD were identified. The prevalence proportion of chronic opioid use increased from 1996 and reached the highest point at 14.26% (95% confidence interval [CI], 13.67%-14.84%) for patients with CD in 2011 and 8.21% (95% CI, 7.88%-8.54%) in patients with UC in 2012. Subsequently, the prevalence proportion of chronic opioid use decreased to 8.88% (95% CI, 8.41%-9.35%) in patients with CD and 4.96% (95% CI, 4.70%-5.21%) in patients with UC by 2021. Throughout the 25-year period, female patients had higher prevalence proportion of chronic opioid use compared with that of male patients. Elderly patients had higher prevalence proportion of chronic opioid use compared with that of adult and young adult patients.

Discussions: Many patients with IBD rely on chronic opioid use as part of their pain management. Further investigations are needed to study the complications and sequelae of chronic opioid use in patients with IBD.

Objectives: We aimed to identify plasma proteins associated with incident Crohn's disease (CD) and ulcerative colitis (UC), develop and validate predictive models for CD and UC risk, and uncover novel protein-based drug targets.

Methods: The study included 46 523 participants from England in the UK. Biobank as the development set and 47 105 participants for internal replication. An external validation set comprised 5807 participants from Scotland and Wales. Plasma proteomic profiling was performed on 2911 proteins.

Results: In the development set, 49 and 34 proteins were significantly associated with incident CD and UC risk, respectively (Bonferroni P < .05). These findings were replicated in the internal replication set. Two-sample Mendelian randomization (MR) analysis identified three proteins (TIMP1, TNFRSF10A, and LTBR) with causal associations for CD and four proteins (CCL20, OSM, NOS2, and CD300E) for UC. Among these, TIMP1 and CD300E represent novel, undrugged targets, while the remaining five are currently druggable. The proteomic-based model, incorporating age, sex, and candidate proteins, demonstrated strong predictive performance in the external validation set, with a C-index of 0.94 (95% CI, 0.88-1.00) for CD and 0.82 (95% CI, 0.73-0.92) for UC. Integrating candidate proteins or the top 10 proteins into clinically based models significantly enhanced risk prediction for both CD and UC.

Conclusions: This study identifies novel plasma protein associations with CD and UC, supported by genetic evidence, and highlights their potential as therapeutic targets. Plasma proteomics significantly improves risk prediction for incident CD and UC compared to traditional clinical models, offering new avenues for drug discovery and personalized risk assessment.

Background: Comorbid psychological distress (anxiety and depression) in inflammatory bowel disease (IBD) is common and associated with poorer outcomes and increased healthcare burden. Scalable and accessible integrated care is needed. This study examined the feasibility of implementing routine digital mental health screening and digital cognitive-behavioral therapy (COMPASS-IBD) for psychological distress in a large IBD service.

Methods: During implementation, distress was identified by screening or IBD clinician referral. Further triage determined eligibility to receive COMPASS-IBD with trainee therapist support (12 weeks). Pre- and post-intervention outcomes examined reach, acceptability, implementation, and potential effectiveness of the new pathway.

Results: Screening was completed by 827 patients (from November 2022 to September 2023), with 196 patients meeting clinical cutoffs and referred for IBD psychology triage. An additional 82 patients were directly referred via IBD clinicians. Of 91 eligible patients, 65 (71.4%) were enrolled into COMPASS-IBD. Distress significantly reduced post-intervention (Patient Health Questionnaire Anxiety and Depression Scale = -6.203; 95% confidence interval, -8.76 to -3.64; P < .001; Cohen's d = -0.553). Symptoms of anxiety, depression, and IBD-related quality of life significantly improved, but IBD symptomatology did not. Full adherence (≥5 online and ≥3 therapist sessions) to COMPASS-IBD was completed by 32.3% of patients. After initially increasing, the IBD psychology waitlist decreased in wait time (30.8%) and number (63.4%) by the end of study implementation. Patients were accepting of the new treatment pathway.

Conclusions: Routine mental health screening and COMPASS-IBD were successfully implemented in an outpatient IBD service, but support from trainee psychologists and the research team was required. This new integrated pathway can identify and treat psychological distress in IBD with minimal service resource.