Inflammatory Bowel Diseases最新文献

Background: Cumulative data suggest that risankizumab is an effective and safe treatment for patients with Crohn's disease (CD). However, most of the data derive from randomized controlled trials or small retrospective studies with short- or mid-term follow-up. This study aimed to assess the long-term effectiveness and safety of risankizumab in a real-world cohort of patients with CD.

Methods: This single-center, retrospective, cohort study included consecutive patients with CD treated with risankizumab from October 2022 to August 2024. A time-to-event analysis was performed for treatment failure, treatment escalation, and CD-related health care utilization. Treatment failure was defined as the need for drug discontinuation due to primary nonresponse, loss of response, or a serious adverse event or the need for IBD (inflammatory bowel disease)-related surgery. Treatment escalation was defined as the need for shortening the dose interval or intravenous reinduction due to breakthrough CD-related symptoms and/or elevated biomarkers, such as C-reactive protein and fecal calprotectin. Health care utilization was defined as CD-related emergency department visit or hospitalization. Patients were followed from start of risankizumab until drug discontinuation or the end of follow-up (October 2024).

Results: The study population consisted of 106 patients with CD (74% receiving prior biological therapies). Patients were followed for a median of 12 [interquartile range (IQR), 6.8-18.8] months; 14 (13%) patients had treatment failure; 24 (23%) had treatment escalation; and 17 (16%) had CD-related health care utilization. Multivariable Cox proportional hazards regression analysis identified penetrating CD as associated with treatment failure [hazard ratio (HR), 5.2; 95% confidence interval (CI), 1.6-17.2; P = .007], while perianal fistulizing CD (HR, 3.3; 95% CI, 1.2-9.4; P = .023) and prior exposure to more than 2 biologics (HR, 5.8; 95% CI, 1.3-26.3; P = .022) were associated with treatment escalation.

Conclusion: In this real-world cohort with long-term follow-up, risankizumab was generally effective in patients with CD. Penetrating CD was associated with treatment failure, while perianal fistulizing CD and prior exposure to more than 2 biologics were associated with treatment escalation.

Background: It has been theorized that age related immunosenescence reduces the risk of developing anti-drug antibodies (ADAs). This has significant implications regarding choice of therapy and need for routine drug monitoring in this group. We investigated the incidence of ADAs in older adults compared to younger adults with inflammatory bowel disease (IBD).

Methods: We conducted a multicenter retrospective cohort study including all older adults (ages ≥60 years) with IBD treated with a tumor necrosis factor inhibitors (TNFi); adults ages 18-59 years old were included in a 4:1 ratio. Kaplan-Meier and Cox regression methods compared longitudinal risk of ADA development between groups. Multivariable models evaluated the association of potential risk factors with ADA development.

Results: 182 (19.7%) older adults and 738 (80.2%) younger adults were included in the study. The risk of ADAs was higher in older adults compared to younger adults (adjusted hazard ratio [aHR] 2.20; 95% confidence interval [CI] 1.44-3.36). Proactive therapeutic drug monitoring (TDM) was inversely associated with ADA development (aHR 0.36; 95% CI 0.25-0.52).

Conclusion: Older adults are more likely to develop ADAs against TNFi compared to younger adults. Proactive TDM may be considered in this population for early identification of ADAs and subtherapeutic trough levels, enabling timely dose escalation or treatment modification.

Background: Branching of colon crypts represents a histological hallmark of inflammatory bowel disease (IBD). The branching of the crypt has been observed to occur both symmetrically and asymmetrically, suggesting two distinct reaction patterns of the colon mucosa. Accurate classification of these two patterns can contribute to improved quantitative description and histologic characterization of IBD subtypes.

Methods: We describe the morphology of branching crypts using manually crafted morphological features. Using a dataset annotated by an expert, we developed and implemented an machine learning model capable of classifying individual crypts based on these features. A multirater survey was conducted to compare interrater agreement between experts and our model.

Results: A classic ensemble model utilizing our manually crafted features achieved a mean balanced accuracy of 0.80, while a deep learning-based model using the segmentation masks achieved a value of 0.79. The survey also showed moderate agreement between the classic ensemble model and senior pathologists.

Conclusions: We present a machine learning model capable of distinguishing both modes of crypt branching patterns. Furthermore, using a hand-crafted feature approach allowed us to directly interpret the classification criteria of our algorithm, rendering it more transparent and interpretable than black box classification models.

Background: In patients with inflammatory bowel disease (IBD), social determinants of health contribute to health inequalities. We aimed to compare patients with IBD treated at a private nonprofit vs public hospital in New York City.

Methods: We performed a retrospective study of adult patients with Crohn's disease or ulcerative colitis with established IBD care. Patient demographics, disease characteristics, healthcare utilization, treatment modalities, and clinical outcomes were collected. Using a series of linear mixed and logistic models, the differences between care at a private nonprofit vs public hospital were assessed while controlling for factors that differed between them.

Results: Our study included 418 patients with IBD, 209 from each hospital. Compared with public hospital patients, private hospital patients were more likely to be White, be non-Hispanic, and have private insurance (all P = .0005) and less likely to face housing instability (P < .0001), face unemployment (P = .0004), be current smokers (P = .03), or be foreign born (P < .0001). Patients at the private hospital were more likely to have multiple anti-tumor necrosis factor (P = .0001) and biologic use (P < .0001). Public hospital patients were less likely to be considered endoscopically adherent (odds ratio [OR], 0.377; P = .001) and more likely to visit the emergency department (OR, 5.01; P < .0001) and be hospitalized (OR, 1.92; P = .05).

Conclusions: Our study is the first to identify significant differences in patient demographics, disease phenotype, treatments and clinical outcomes between patients treated for IBD at a private nonprofit vs public hospital. Our data suggest that social determinants of health drive disparities in the utilization of healthcare facilities.

Background: Data on upadacitinib therapy for pediatric acute severe ulcerative colitis (ASC) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as a salvage therapy in pediatric ASC.

Methods: Children and adolescents with ASC who were treated with upadacitinib for the induction of remission were enrolled in this retrospective multicenter study. Demographic, clinical, and laboratory data as well as adverse events (AEs) were recorded after the 8-week induction period and throughout 26 weeks of therapy. Analyses were based on the intention-to-treat principal.

Results: Twenty-two patients were included (median age 15.7 [interquartile range 13.5-16.6] years, 12 hospitalized), all with anti-tumor necrosis factor (TNF) therapy refractory disease. Ten patients were treated with corticosteroids at baseline, and upadacitinib was added to an ongoing biologic therapy in five patients. At week 8 of therapy, 11 (50%) patients of the cohort remained colectomy-free and in corticosteroid-free clinical remission (CFR), and 17 (77%) patients remained colectomy-free. Normal C-reactive protein (CRP) was achieved in 9 of 11 (82%) patients who were in CFR, and fecal calprotectin <150 mcg/g in 4 of 6 (67%) patients with available data. By week 26, 14 (64%) were in CFR and 16 (73%) patients remained colectomy-free. All these patients had normal CRP levels, and 4 of 7 patients with available data had fecal calprotectin <150 mcg/g. Twelve patients reported AEs, including two serious AEs of an appendiceal neuroendocrine tumor and cytomegalovirus colitis.

Conclusion: Upadacitinib is an effective induction therapy for children and adolescents with ASC after failing anti-TNF.

Background: A small but significant proportion of patients with Crohn's disease (CD) will ultimately require a permanent ileostomy. So far, research has focused primarily on clinical and surgical recurrence rates in the ileum, leaving endoscopic recurrence largely unexplored. The aim of this study was to explore the endoscopic ileal recurrence rate in patients with a long-term ileostomy and to identify potential risk factors.

Methods: We performed a retrospective study of adult CD patients with a long-term ileostomy (≥12 months) at a tertiary referral center.

Results: Through an electronic health record database search, we were able to identify 150 patients. One hundred sixteen patients (77.3%) underwent at least one endoscopic examination of the ileum. Ileal recurrence was detected in 46/116 (39.7%). The 1, 3, and 5-year endoscopic recurrence rates were 11.2%, 27.3%, and 33.0%, respectively. Patients with earlier ileal involvement (hazard ratio [HR] 1.99, 95% confidence interval [CI] 1.09-3.62; P = .02) or previous biological therapy (HR 2.48, 95% CI 1.25-4.89; P = .01) were at higher risk. Fecal calprotectin in ileostomy effluent accurately predicted endoscopic inflammation at a cutoff of 170 mcg/g (sensitivity 77.8%, specificity 94.7%, accuracy 89.9%).

Conclusions: In this retrospective study, 77.3% of ileostomy patients underwent endoscopic assessment during follow-up. Ileal recurrence was detected in 39.7% of patients who underwent endoscopic evaluation. Patients with ileal involvement or preoperative exposure to biologics had the highest risk of recurrence. These patients might benefit from endoscopic monitoring. Fecal calprotectin is a reliable noninvasive marker for detecting ileal inflammation.

This narrative review summarizes the current knowledge on using intestinal ultrasonography (IUS) to evaluate disease activity in patients with Crohn's disease (CD) and explores its potential role in clinical trials. Current trial endpoints and their limitations are discussed, highlighting the need for more patient-centric approaches, including increased use of magnetic resonance enterography (MRE) and IUS. Intestinal ultrasonography offers several advantages: it is noninvasive, requires no sedation, bowel preparation, or exposure to ionizing radiation, and enables real-time assessment of disease activity. It also demonstrates high sensitivity and specificity for detecting transmural inflammation and complications such as strictures, abscesses, and fistulas. Compared with cross-sectional imaging modalities like MRE and computed tomography, IUS is more patient-friendly, cost-effective, and suitable for point-of-care examination. However, challenges remain, including the lack of a universally accepted disease activity scoring system for MRE or IUS, despite the development and validation of several scoring tools. Key unmet needs include standardization of image acquisition and reporting, adequate training of healthcare professionals, improved access to equipment, and reimbursement pathways. Intestinal ultrasonography is increasingly being integrated into clinical trials to assess transmural inflammatory changes in CD, with IUS-based measures of transmural remission or response showing promise as potential endpoints. Although its advantages are clear, addressing these unmet needs is essential to broaden the adoption of IUS in both clinical trials and routine clinical practice.

Background: Research is limited on the impacts of menopause, defined as the permanent cessation of ovarian function and decline of reproductive hormones, on gastrointestinal symptom severity and disease progression in women with inflammatory bowel disease (IBD). This review synthesizes current evidence on the impact of menopause, menopause transition, and hormonal therapy (HT) on disease activity, IBD and menopause symptom severity, and disease progression among individuals with IBD.

Methods: A systematic literature review was reported following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and preregistered at PROSPERO (CRD42024564901). Five databases were searched without date restrictions. Data extraction and risk-of-bias assessment were performed independently by multiple reviewers. Results were qualitatively synthesized.

Results: Of 1667 records, 15 studies met inclusion criteria (5 cohort, 3 case-control, 7 cross-sectional) with IBD sample sizes from 37 to 1367. Evidence on HT and IBD risk was mixed: some studies linked HT to increased ulcerative colitis risk while others found no significant association after adjusting for confounders. Women with IBD experience earlier menopause than healthy control subjects. While most women reported no change in IBD symptoms postmenopause, a minority reported symptom worsening. HT may reduce flare severity. Women with IBD reported more severe vulvovaginal symptoms and had distinct vaginal microbiome profiles compared with healthy control subjects.

Conclusions: Few studies have explored the relationship between menopause and IBD. There is a need for continued research on the relationship between IBD disease activity and menopause symptoms to create tailored interventions to improve women's health with IBD across the lifespan.