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A Real-World Comparison of Drug Trough Levels between Patients Experiencing a Secondary Non-Immune Loss of Response and those Maintaining a Response to Infliximab on Long-Term Maintenance Therapy for Inflammatory Bowel Disease

Introduction: A secondary loss of response (LOR) to Infliximab (IFX) therapy for inflammatory bowel disease (IBD) is typically associated with low IFX trough levels, often with high levels of neutralizing antibodies to infliximab (ATI). A small subset of patients on long term therapy experience a “non-immune” LOR, without ATI and with desired IFX trough levels ≥5 mcg/ml, regarded as a LOR to the mechanism of action of IFX. However, this currently accepted IFX goal level is largely derived from observations of patients within the first year of therapy and may not apply to those on treatment beyond 1 year. Methods: Retrospective review of all IBD patients receiving IFX infusions for ≥12 months with at least 1 IFX trough and ATI measurement beyond 12 months. Chart review of all patients with absent ATI and an IFX trough ≥ 5 mcg/ml, classify as LOR vs. non-LOR based on physician assessment, with a comparison of IFX troughs between the two groups. Results: Of 167 patients using IFX ≥ 12 months, 13 (7.8%) experienced a non-immune secondary LOR. The mean duration of IFX use was over 3 years for both LOR and non-LOR patients. The mean IFX trough for those with LOR was greater than for those without LOR, 18.5 mcg/ml vs. 13.1 mcg/ml, p =0.110. Conclusion: Our results did not demonstrate lower IFX levels among patients experiencing secondary non-immune LOR on long term therapy. Our results do not redefine the therapeutic IFX goal levels for those patients on long term therapy and suggest that underdosing of IFX is not the cause of secondary LOR.

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Ultra-Processed Foods Consumption Is Positively Associated with the Clinical Activity of Inflammatory Bowel Diseases: A Cross-Sectional Single-Center Study

Introduction: Western diet pattern and its food components have been suggested to impact inflammatory bowel diseases (IBDs) clinical course. However, the importance of food processing level is uncertain. We aimed to evaluate whether the intake of foods with varying processing levels is associated with disease activity in IBD patients. Methods: This cross-sectional study was performed at a tertiary center between August 2019 and June 2022. Consecutive adult IBD patients were recruited. Clinical disease activity was defined using HBI (Crohn’s disease) and SCCAI (ulcerative colitis). Dietary intake was assessed using a food frequency questionnaire (FFQ) and a dedicated validated processed food questionnaire (PFQ) that categorizes dietary intake into three groups of processed food levels: unprocessed/minimally processed, processed, and ultra-processed. Adjusted odds ratios for active disease were determined using a multivariable logistic regression. Results: A total of 242 IBD patients (62.8% Crohn’s disease patients) were enrolled, of whom 73.1% were in clinical remission. A higher (upper tertile vs. lowest tertile) unprocessed/minimally processed foods consumption was negatively associated with active disease (OR = 0.38, 95% CI: 0.14–0.99), while high consumption of ultra-processed foods (UPFs) was positively associated with clinically active disease (OR = 3.82, 95% CI: 1.49–9.8). Consumption of UPF groups, almost invariably, was positively associated with clinically active disease, while consumption of the ultra-processed meats group had the strongest association (OR = 4.45, 95% CI: 2.07–9.79). Conclusion: Higher consumption of UPFs is positively associated with clinically active IBD, while higher consumption of unprocessed/minimally processed foods may be protective. Prospective studies are needed to confirm these associations.

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Intestinal Ultrasonography Diagnostic Performance and Feasibility in IBD during Pregnancy: A Systematic Review and Narrative Synthesis

Introduction: Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are associated to poor maternal and foetal outcomes during pregnancy, requiring a strict monitoring of the disease activity, preferably with non-invasive modalities. There are numerous data confirming intestinal ultrasonography (IUS) accuracy and efficacy for the detection of IBD disease activity and complications, but data in pregnant IBD patients are scarce. We aimed to evaluate the diagnostic performance and feasibility of IUS to monitor IBD activity throughout pregnancy. Methods: A systematic literature review was performed to identify studies on the use of ultrasound modality in pregnant inflammatory bowel disease women from the date of inception until April 2024 using MEDLINE, Cochrane Library, EMBASE, and ISI Web of Science databases, with keywords including (1) ultrasound/ultrasonography, (2) pregnancy, and (3) IBD (CD and UC). Additional relevant studies were identified from cross-referencing and hand-searches of references of the retrieved articles. We included fully published observational studies and abstracts. Results: Overall, five studies have been selected from 264 citations. All studies were highly heterogeneous in the definition of disease activity as reference standard, IUS protocols, and outcomes. Two of them used a cut-off value of faecal calprotectin (FCP) >100 μg/g. In one of them, clinical scores were used when the FCP value was ≥100–249 μg/g and FCP ≥250 μg/g was considered as an active disease independently of clinical scores. Only one study used a single reference standard with a Harvey-Bradshaw Index (HBI) >4. Across these 3 studies, results suggest a relatively good specificity (range 83–98%) but low sensitivity (range 33–84%) to detect disease’s activity. Only 1 study analysed IUS performance in detecting remission with a sensitivity of 80% and a specificity of 92% compared to the reference standard. The size of the uterus limits the visualization of the terminal ileum and the sigmoid from the second trimester and the third trimester, respectively. The evaluation of the rectum remains limited. Conclusion: IUS appears to offer a practical, readily available and non-invasive means of monitoring disease activity in IBD pregnant women. However, existing literature on IUS accuracy is limited and further studies with standardized reference comparator are needed.

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What Happens to Patients with Inflammatory Bowel Disease Who Are Intolerant to Thiopurines?

Introduction: The clinical consequences for patients with inflammatory bowel disease (IBD) who stop treatment owing to side effects have not been fully investigated. Methods: This retrospective observational study aimed to compare patients who discontinued thiopurine treatment due to side effects with those who tolerated thiopurine treatment in the use of other IBD drugs, surgery, and fecal calprotectin values in the first 5 years after the start of thiopurine treatment. Results: The proportion of patients with IBD who initiated thiopurine treatment at our clinic was 44% (32% ulcerative colitis and 64% Crohn's disease) and 31% (n = 94) of those patients had to stop thiopurine treatment within 5 years due to side effects. Patients who discontinued thiopurine treatment due to intolerance were significantly older (median age 33 vs. 27 years, p = 0.003), significantly more often used prednisolone (89 vs. 76%, p = 0.009), and used to a lesser extent TNF inhibitors at the start of thiopurine treatment (3% vs. 9%, p = 0.062). Budesonide treatment and non-TNF inhibitor second-line therapy were significantly more commonly used in patients who discontinued thiopurine treatment owing to side effects, but there were no statistically significant differences in the use of other treatments. The proportion of patients with a median FC >200 μg/g was significantly higher during follow-up in patients with UC who discontinued thiopurine treatment owing to side effects. Conclusions: Patients who discontinued thiopurines owing to side effects were prescribed more budesonide and non-TNF inhibitor second-line therapy, but there were no differences in the use of TNF inhibitors, prednisolone, or surgery.

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The Utility of Magnetic Resonance Enterography and Double Balloon Enteroscopy-Assisted Endoscopic Balloon Dilatation for Small Bowel Strictures in Crohn’s Disease: A Retrospective Observational Study

Introduction: Crohn’s disease (CD) of the small bowel is associated with a severe course and increased risk of complications. Strictures at this location are challenging to diagnose and out-of-reach of colonoscopy. We aimed to evaluate the detection rate of small bowel strictures with magnetic resonance enterography (MRE) and assess the efficacy of double balloon enteroscopy-assisted endoscopic balloon dilatation (DBE-assisted EBD) in managing these strictures. Methods: A retrospective study included all patients with DBE-assisted EBD of small bowel strictures in CD in our facility. All patients had MRE to detect strictures prior to the dilatation. Sequential dilatation protocol was performed using through-the-scope (TTS) working channel balloons. The outcomes included technical success defined by the passage of the enteroscope post-dilatation, resolution of symptoms, and the requirement of repeated procedures or surgery during 12 months of follow-up. Results: Twenty DBE-assisted EBDs of small bowel strictures were attempted during 13 DBE procedures in 10 patients (6 males, median age 42). MRE identified 75% of the strictures with 100% accuracy in localisation. Retrograde DBE was the approach in 16/20 (80%) strictures. Anaesthetic intubation was used in 8/20 (40%). DBE reached 19/20 strictures. All the reached strictures were dilated successfully; the technical success following dilatation was 72.2%. The median DBE insertion time with TTS balloon dilatation was 66 min. Three patients required follow-up dilatations within 2–3 months. Surgery was not needed during the follow-up period. Conclusions: MRE is essential in diagnosing and localising small bowel strictures in CD. DBE reached 95% of strictures with successful dilatation. Immediate technical success was high, and safety was demonstrated. Planned repeat procedures for sequential dilatation were performed in a few patients. Surgical resection was avoided in all patients.

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Predicting Therapeutic Intervention for Patients with Quiescent Crohn’s Disease Using the Small Bowel Capsule Endoscopy Score

Introduction: Small bowel (SB) capsule endoscopy (SBCE) is a sensitive modality for screening the entire SB of patients with Crohn’s disease (CD); however, the prognostic impact of the results is unclear. We evaluated the ability of the SBCE score to predict therapeutic intervention for patients with CD and SB lesions without clinical symptoms as well as negative C-reactive protein (CRP) levels. Methods: Fifty-six patients who underwent a patency evaluation and had a CD activity index (CDAI) score <150 mg/dL and CRP level <0.5 mg/dL were included. Twenty-one and 35 patients had CD classified as Montreal classifications L1 and L3, respectively. The initial SBCE scores were subsequently grouped according to the presence or absence of intervention based on cutoff values. We examined whether the scores could predict the need for therapeutic intervention at 1 year, 2 years, and 5 years. The CD activity in capsule endoscopy (CDACE) score was used as the SBCE score. Results: The median observation period was 1,326 days. Twenty-one patients received therapeutic intervention. There were significant differences between patients with and without treatment intervention according to the CDACE cutoff value of 420 at 1 year, 2 years, and 5 years. Significant differences between patients with Montreal classification L1 with and without intervention were observed at 1 year and 2 years. The CDACE score was moderately and strongly correlated with the Lewis score and capsule endoscopy CDAI score, respectively (Spearman rank correlation coefficient: ρ = 0.6462 and ρ = 0.9199, respectively; p < 0.0001). Conclusion: A CDACE score ≥420 is predictive of intervention after 1 year for patients with CD, a CDAI score <150, and a CRP level <0.5 mg/dL. A larger study with a prospective design is necessary to validate our findings.

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Factors of Self-Care Agency in Patients with Inflammatory Bowel Disease in Japan

Introduction: Currently, no self-care measurement tool specific to inflammatory bowel disease (IBD) exists in Japan. The Instrument for Diabetes Self-care Agency (IDSCA) is a reliable and valid self-care measurement tool for patients with diabetes. Factors affecting self-care ability assessed by IDSCA appear to meet the requirements for patients with IBD. Therefore, we created a self-care ability measurement tool adapted from IDSCA as an original draft for the Instrument for IBD Self-care Agency and extracted factors and items required to measure the self-care ability of patients with IBD. Methods: An anonymous questionnaire survey was distributed among 226 patients. Exploratory factor analysis examined the relationship of factors from multiple perspectives, identified factors based on their content, and confirmed their internal consistency. Statistical analyses were performed using JMP® 14.0.0. Results: Five factors with 23 items were extracted from the IDSCA, including ability to build a human support system, ability to acquire knowledge, ability to maintain self-care, ability to self-manage, and ability to self-assess. Cronbach’s alpha was 0.765–0.861 for each factor and 0.904 for the entire scale. Conclusion: We could identify the self-care agencies of patients with IBD, including 5 factors and 23 items. Focusing on these self-care factors may provide critical information to guide nurses’ self-care interventions.

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A Retrospective Observational Study of Patterns of Biologic Drug Change in Inflammatory Bowel Disease

Introduction: Multiple therapies are currently available for inflammatory bowel disease (IBD); it is therefore crucial to understand patterns of drug change. This study aimed to examine the patterns of biological drug change and identify predictors of change in patients with IBD. Methods: We performed a retrospective study of patients diagnosed with IBD who were initiated on treatment with biologics between June 2017 and October 2022. The study's primary objective was to describe biologic drug change patterns. Secondary outcomes included identifying predictors of drug change. Results: 910 patients were screened; 475 patients were eligible, 319 (67%) had Crohn’s disease (CD), and 253 (53.3%) were males. The most selected first and second choices of biologic were adalimumab (58.2% and 39.1%, p < 0.001) and infliximab (37.6% and 48.9%, p = 0.004) for both CD and ulcerative colitis (UC), respectively. On multiple regression analysis, a history of venous thromboembolism (VTE) (OR = 3.60, p = 0.025) and smoking (OR = 0.34, p = 0.026) were associated with drug change for all patients. When stratified by disease subtype, drug change was associated with a diagnosis made between age 17 and 40 years (OR = 0.46, p = 0.024) and extra-intestinal manifestations (OR = 2.07, p = 0.015) in CD while selecting vedolizumab as the first biologic (OR = 0.30, p = 0.041), male gender (OR = 2.40, p = 0.043), and history of VTE (OR = 7.32, p = 0.031) were associated with drug change in UC. Conclusions: Despite introducing several new biologics, anti-TNF therapies remain the preferred first and second choice of biologics for patients with IBD. Multiple predictors of drug change over time exist for both diseases. Selecting vedolizumab as the first biologic for UC is associated with a lower risk of drug change.

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