Disease Activity In Colitis Research Articles

Intestinal ultrasound scan predicts corticosteroid failure and colectomy risk in patients with ulcerative colitis.

Intestinal ultrasound (IUS) is an emerging modality for assessing disease activity, extent, and treatment response in ulcerative colitis. This study aimed to evaluate the potential of IUS in predicting severe flares, the need for rescue therapy (corticosteroid failure), and colectomy in patients with ulcerative colitis. We conducted a retrospective review of medical records, collecting clinical and IUS data. The Milan Ultrasound Criteria (MUC) score was used to assess ulcerative colitis severity. Group comparisons were performed to identify differences in MUC scores between mild-to-moderate and severe ulcerative colitis, between steroid responders and nonresponders, and between patients who underwent colectomy and those who did not. Receiver operating characteristic (ROC) analysis was used to predict outcomes in patients with ulcerative colitis. This analysis included 102 patients with ulcerative colitis categorized as mild/moderate (60) or severe (42). MUC scores were significantly higher in the severe ulcerative colitis group compared with the mild/moderate group ( P < 0.001). Analysis (using ROC) identified a cutoff MUC score of >8.54 to indicate severe ulcerative colitis with good sensitivity (64.29%) and excellent specificity (93.33%). Similarly, a cutoff of MUC > 10.54 showed promise in predicting corticosteroid failure, with acceptable sensitivity (50%) and high specificity (90.91%). Finally, a cutoff MUC score >12.5 demonstrated potential for predicting colectomy, exhibiting moderate sensitivity (55.56%) but excellent specificity (96.97%). IUS may be useful for differentiating severe ulcerative colitis from mild-to-moderate disease, identifying early stage failure of corticosteroid therapy, and predicting the potential need for colectomy.

An artificial intelligence-driven scoring system to measure histological disease activity in ulcerative colitis.

Assessment and scoring of histological images in Ulcerative colitis (UC) is prone to inter- and intra-observer variability. This study aimed to investigate whether an artificial intelligence (AI) system developed using image processing and machine learning algorithms could measure histological disease activity based on the Nancy index. A total of 200 histological images of patients with UC were used in this study. A novel AI algorithm was developed using state-of-the-art image processing and machine learning algorithms based on deep learning and feature extraction. The cell regions of each image, followed by the Nancy index, were manually annotated and measured independently by four histopathologists. Manual and AI-automated measurements of the Nancy index score were conducted and assessed using the intraclass correlation coefficient (ICC). The 200-image dataset was divided into two groups (80% was used for training and 20% for testing). Intraclass correlation coefficient statistical analyses were performed to evaluate the AI tool and used as a reference to calculate the accuracy. The average ICC among the histopathologists was 89.3 and the average ICC between histopathologists and the AI tool was 87.2. The AI tool was found to be highly correlated with histopathologists. The high correlation of performance of the AI method suggests promising potential for inflammatory bowel disease clinical applications. A standardized automated histological AI-driven scoring system can potentially be used in daily inflammatory bowel disease practice to reduce training needs and resource use, eliminate the subjectivity of the pathologists, and assess disease severity for treatment decisions.

Comprehensive profiling of the human fecal proteome from IBD patients with DIA-MS enables evaluation of disease-relevant proteins.

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is characterized by chronic gastrointestinal inflammation. A high unmet need exists for noninvasive biomarkers in IBD to monitor changes in disease activityand guide treatment decisions. Stool is an easily accessed, disease proximal matrix in IBD, however the composition of the IBD fecal proteome remains poorly characterized. A data-independent acquisition LC-MS/MS approach was used to profile the human fecal proteome in two independent cohorts (Cohort 1: healthy n=5, UC n=5, CD n=5, Cohort 2: healthy n=20, UC n=10, and CD n=10) to identify noninvasive biomarkers reflective of disease activity. 688 human proteins were quantified, with 523 measured in both cohorts. In UC stool 96 proteins were differentially abundant and in CD stool 126 proteins were differentially abundant compared to healthy stool (absolute log2 fold change>1, p-value<0.05). Many of these fecal proteins are associated with infiltrating immune cells and ulceration/rectal bleeding, which are hallmarks of IBD pathobiology. Mapping the identified fecal proteins to a whole blood single-cell RNA sequencing data set revealed the involvement of various immune cell subsets to the IBD fecal proteome. Findings from this study not only confirmed the presence of established fecal biomarkers for IBD, such as calprotectin and lactoferrin, but also revealed new fecal proteins from multiple pathways known to be dysregulated in IBD. These novel proteins could serve as potential noninvasive biomarkers to monitor specific aspects of IBD disease activity which could expedite clinical development of novel therapeutic targets.

Accurate, Robust, and Scalable Machine Abstraction of Mayo Endoscopic Subscores From Colonoscopy Reports.

The Mayo endoscopic subscore (MES) is an important quantitative measure of disease activity in ulcerative colitis. Colonoscopy reports in routine clinical care usually characterize ulcerative colitis disease activity using free text description, limiting their utility for clinical research and quality improvement. We sought to develop algorithms to classify colonoscopy reports according to their MES. We annotated 500 colonoscopy reports from 2 health systems. We trained and evaluated 4 classes of algorithms. Our primary outcome was accuracy in identifying scorable reports (binary) and assigning an MES (ordinal). Secondary outcomes included learning efficiency, generalizability, and fairness. Automated machine learning models achieved 98% and 97% accuracy on the binary and ordinal prediction tasks, outperforming other models. Binary models trained on the University of California, San Francisco data alone maintained accuracy (96%) on validation data from Zuckerberg San Francisco General. When using 80% of the training data, models remained accurate for the binary task (97% [n = 320]) but lost accuracy on the ordinal task (67% [n = 194]). We found no evidence of bias by gender (P = .65) or area deprivation index (P = .80). We derived a highly accurate pair of models capable of classifying reports by their MES and recognizing when to abstain from prediction. Our models were generalizable on outside institution validation. There was no evidence of algorithmic bias. Our methods have the potential to enable retrospective studies of treatment effectiveness, prospective identification of patients meeting study criteria, and quality improvement efforts in inflammatory bowel diseases.

Combined gray scale ultrasonography and doppler diagnostic tools with strain elastography in assessment of inflammatory bowel disease in pediatrics patients.

Intestinal changes in inflammatory bowel disease (IBD) are frequently observed on ultrasound. Invasive diagnostic procedures are often employed to differentiate between the main types of IBD and detect complications. Ultrasound Strain Elastography (SE) is a promising non-invasive technique for detecting intestinal changes and assessing inflammatory activity in pediatric IBD. This research aims to evaluate the diagnostic performance of conventional ultrasound, color Doppler, and SE in assessing inflammatory bowel disease in pediatric patients, both separately and in combination as additional tools. Forty patients (18 females and 22 males) initially diagnosed with IBD through clinical and endoscopic biopsy, along with 20 healthy controls, underwent conventional ultrasound, color Doppler, SE, and laboratory evaluations, including CBC, ESR, CRP, Fecal calprotectin, and assessment of IBD activity using PIBDAI. Conventional ultrasound, color Doppler, and SE significantly contributed to detecting disease activity and intestinal changes in IBD (p < 0.001; 95% CI 0.79-1.100), demonstrating better sensitivity in combination compared to each method individually. The combined approach showed 100% sensitivity, 84% specificity, 78.6% precision (Positive Predictive Value), 100% Negative Predictive Value, and an overall accuracy of 92%. The addition of Color Doppler and SE parameters to grayscale ultrasound provides diagnostic value comparable to endoscopy, histopathology, and laboratory markers in detecting inflammatory activity and intestinal changes in IBD. This combined approach can help avoid unnecessary invasive techniques for follow-up.

Anti-integrin αvβ6 autoantibodies are a potential biomarker for ulcerative colitis-like immune checkpoint inhibitor-induced colitis

BackgroundNo specific biomarker for immune checkpoint inhibitor (ICI)-induced colitis has been established. Previously, we identified anti-integrin αvβ6 autoantibodies in >90% of patients with ulcerative colitis (UC). Given that a subset of ICI-induced colitis is similar to UC, we aimed to clarify the relationship between such autoantibodies and ICI-induced colitis.MethodsSerum anti-integrin αvβ6 autoantibody levels were compared between 26 patients with ICI-induced colitis and 157 controls. Endoscopic images of ICI-induced colitis were centrally reviewed. Characteristics of anti-integrin αvβ6 autoantibodies in the ICI-induced colitis patients were compared with those of UC patients.ResultsAnti-integrin αvβ6 autoantibodies were found in 8/26 (30.8%) patients with ICI-induced colitis and 3/157 (1.9%) controls (P < 0.001). Patients with anti-integrin αvβ6 autoantibodies had significantly more typical UC endoscopic features than those without the autoantibodies (P < 0.001). Anti-integrin αvβ6 autoantibodies in ICI-induced colitis patients were associated with grade ≥3 colitis (P = 0.001) and steroid resistance (P = 0.005). Anti-integrin αvβ6 autoantibody titers correlated with ICI-induced colitis disease activity. Anti-integrin αvβ6 autoantibodies of ICI-induced colitis exhibited similar characteristics to those of UC.ConclusionsAnti-integrin αvβ6 autoantibodies may serve as potential biomarkers for the diagnosis, classification, risk management, and monitoring the disease activity, of ICI-induced colitis.

A250 CYTOKINE MULTI-OMICS AND MACHINE LEARNING IDENTIFY MIP1ALPHA AS A NOVEL MEDIATOR IN INFLAMMATORY BOWEL DISEASE

Abstract Background Macrophage inflammatory protein 1 alpha (MIP1a) is a proinflammatory cytokine previously related to murine models of inflammatory bowel disease (IBD), but not definitively in the human disease. MIP1a acts as a chemoattractant of immune cells from the blood to the gut mucosa. We aimed to delineate the alterations to MIP1a and macrophages in relation to a range of IBD severity. Aims To characterize the changes to MIP1a production and localization in response to disease activity in IBD. Methods Both IBD (n=63) and control patients (n=118) were enrolled in this study (HSREB 6033229). Cytokine profiles were investigated using a 17-plex multi-fluorescent bead-based immunoassay (FirePlex, Abcam, Cambridge, UK) on serum from a subset of patients. Disease activity and macrophage levels were extracted from the clinical record. Activity was quantified using the Physician Global Assessment Score. Machine learning (ML) was performed with custom R scripts utilizing the tidymodels package (version 1.1) to determine the optimal model. Immunohistochemistry (IHC) was used to localize MIP1a in patient biopsies and quantified using QuPath software (v0.4). Results An extreme gradient boost ML model was found to have optimal sensitivity and specificity for predicting disease activity based on serum cytokine levels. Within this model lower levels of serum MIP1a were associated with higher severity of IBD activity. However, in GI mucosal biopsies, the percentage of MIP1a positive cells in colon tissue increased with the severity of IBD. Macrophage concentrations in the peripheral blood were higher in patients on prednisone, and relatively similar across all other medications used in our cohort. Conclusions With the data collected, we identify MIP1a as a possible prognostic tool for quantifying IBD activity. Funding Agencies CIHR

A225 ASSESSMENT OF BEDSIDE INTESTINAL ULTRASOUND IN MONITORING CROHN’S DISEASE ACTIVITY

Abstract Background Bedside intestinal ultrasound (IUS) is an evolving modality in monitoring disease activity and assessing complications in inflammatory bowel disease (IBD). The easy-tolerability and immediate accessibility to results for expedited clinical decision-making contribute to the growing global attraction of IUS integration into IBD care. Fecal calprotectin (FC) is a known, non-invasive tool to assess disease activity in IBD. However, it comes with limitations. Aims To assess the efficacy of IUS in monitoring Crohn’s Disease (CD) compared to FC level. Methods We conducted a retrospective observational study in patients with confirmed CD at a certified IUS gastroenterologist’s outpatient clinic in Saskatoon. Patients’ charts undergoing IUS between February 2022 and April 2023 were reviewed. Patients with CD and available FC results within a month of IUS performance were identified. Age, gender, disease character, clinical symptoms (Harvey-Bradshaw Index (HBI)), FC levels, and IUS bowel wall thickening (BWT) were collected. The cut-off for FC levels and BWT for disease activity were ampersand:003E250 μg/g and ampersand:003E3 mm, respectively. The correlation between IUS BWT and FC levels was analyzed based on the Pearson correlation. Results Among a total of 178 chart reviews, 71 patients were identified. The median age was 49 years, 52.1% were males and 47.8% were females. 35 (49.3%) ileal CD, 35 (49.3%) ileocolonic and 1 (1.4%) colonic CD were identified. The HBI score verified 67.6% mild disease, 19.7% moderate, 11.2% in remission, and 1.4% severe disease. The Pearson correlation coefficient (r) between FC levels and BWT findings on IUS was r = 0.29 (P ampersand:003C0.0001), indicating a weak positive correlation. Conclusions A positive but weak correlation exists between bowel wall thickening in IUS and FC level in monitoring CD. Recognizing FC limitations, future multi-center, larger cohort studies need to be done to investigate this correlation further. Funding Agencies None

A266 TISSUE-SPECIFIC FUNCTION OF THE CIRCADIAN GENE, BMAL1, DURING COLITIS RECOVERY

Abstract Background The circadian clock is a self-sustained molecular oscillator which drives 24-hour physiological rhythms in nearly every cell of the body. It consists of the genes Bmal1 and Clock that positively regulate Cry and Per, their negative regulators, resulting in a 24-hour transcription/translation feedback cycle. Shift work, which causes disruptions to 24-hour physiological rhythms, has been linked with an increased incidence of inflammatory bowel disease (IBD). Aims We have previously established that mice lacking the non-redundant circadian regulator, Bmal1, exhibit more severe colitis compared to controls. The loss of Bmal1 also negatively impacts post-colitis regeneration and recovery. However, the role of Bmal1 in specific cell types remains unknown in regard to regenerative capacity following colitis. The intestinal stem cell niche includes stromal cells that provide signaling factors to regulate the proliferation of epithelial cells in the colonic crypt. Methods To test the role of the circadian clock in these cell types, we conditionally disrupted Bmal1 in intestinal epithelial versus stromal cells using VilCre/+;Bmal1flox/flox and PdgfraCre/+;Bmal1flox/flox mice, respectively. Dextran Sulfate Sodium (DSS) was applied to induce acute colitis, disease progression was evaluated, and regeneration at different stages of recovery was analyzed. We hypothesize that the cell-specific disruption of Bmal1 in both intestinal epithelial and stromal cells negatively impacts the regenerative capacity following colitis, leading to delayed recovery and increased inflammation. Results No differences in survival and colitis disease activity were observed between Vil+/+;Bmal1flox/flox control and VilCre/+;Bmal1flox/flox but increases in lesion number, inflammation, and disrupted recovery are evident in VilCre/+;Bmal1flox/flox colons histologically. Whereas control animals are able to recover two weeks following DSS treatment, regenerative proliferation is still present in conditional knockouts. Thus, Bmal1 is required in intestinal epithelial cells for efficient repair. Preliminary results in the PdgfraCre/+;Bmal1flox/flox conditional stromal mutanats do not show differences in survival or disease severity, and we are currently evaluating effects on regeneration. Conclusions Our results support a critical role for Bmal1 in intestinal epithelial cells during post-colitis regeneration and recovery. Funding Agencies CCC, CIHR

A230 SARCOPENIA IN PRIMARY SCLEROSING CHOLANGITIS AND INFLAMMATORY BOWEL DISEASE IN PAEDIATRICS AND CLINICAL IMPLICATIONS

Abstract Background Sarcopenia is defined in paediatrics as a decrease in muscle mass for a given age. The coexistence of primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) is recognized to be a distinct entity with a distinct phenotype. However, to date, there is no study that has assessed the prevalence of sarcopenia and its clinical implications in paediatric PSC-IBD, compared to paediatric colitis. Aims We first aimed to determine whether sarcopenia is more prevalent in paediatric PSC-IBD than children with colitis without liver disease. Our secondary aim was to explore the prognostic implications of sarcopenia in paediatric PSC-IBD both for liver and IBD outcomes. Methods This was a single-center retrospective cohort study including paediatric IBD patients with and without PSC who underwent magnetic resonance enterography (MRE) for clinical care. Psoas muscle area (PMA) at the L4-5 intervertebral disc level was calculated. Sarcopenia was defined as PMA ampersand:003C 3rd percentile for age and sex. The association between PSC and sarcopenia was examined using logistic regression, adjusting for variables selected using change in estimate method. Survival analysis was used to examine the association between sarcopenia and IBD/liver outcomes. Results A total of 85 IBD patients were included – 31 PSC-IBD and 54 colitis controls. Both groups had male predominance. A higher proportion of children with PSC-IBD had pancolitis (Pampersand:003C0.001), and PSC-IBD patients had less severe clinical IBD disease activity than controls (P=0.003). Sarcopenia was present in 39% PSC-IBD and 18% colitis (odds ratio (OR) 2.7, 95%CI 1.02-7.53, P=0.044). Adjusting for endoscopic Mayo score and biologic therapy exposure prior to MRE, the adjusted OR for the association between PSC and sarcopenia was 4.22, 95%CI 1.32-13.44, P=0.015. Sarcopenic patients were younger than non-sarcopenic patients (mean 12.4(SD2.9) years versus 14.3(SD2.3) years, P=0.003), and also had lower weight and height (Pampersand:003C0.001, P=0.002, respectively). Sarcopenia was not a risk factor for escalation to biologics and/or surgery (hazards ratio (HR) 1.18, 95%CI 0.55-2.50, P=0.67) nor for progression to liver fibrosis and/or portal hypertension (HR 0.40, 95%CI 0.044-3.54, P=0.40). Conclusions Sarcopenia was 4 times more frequent in PSC-IBD compared to colitis controls in our cohort, after accounting for differences in IBD severity and biologic exposure. Sarcopenia may represent an additional feature that is distinct to PSC-IBD versus colitis without associated PSC. Funding Agencies None

Ultra-Processed Food, Disease Activity, and Inflammation in Ulcerative Colitis: The Manitoba Living With IBD Study.

The purpose of this study was to investigate the relationship between ultra-processed food (UPF) consumption and (i) symptomatic disease and (ii) intestinal inflammation among adults with inflammatory bowel disease (IBD). We identified participants (Crohn's disease [CD] and ulcerative colitis [UC]) from the Manitoba Living with IBD study. Active disease was defined using the IBD Symptom Inventory (score >14 for CD; >13 for UC); fecal calprotectin was measured for intestinal inflammation (>250 μg/g). Diet data were collected using the Harvard Food Frequency Questionnaire. UPF consumption was determined by the NOVA classification system. Percentage of energy consumption from UPFs was calculated and divided into 3 tertiles (T1 = low; T3 = high). Multiple linear regression analysis was used for active disease and inflammation predicted by UPF consumption. Among 135 participants (65% with CD), mean number of episodes of active disease (14.2 vs 6.21) and active inflammation (1.6 vs 0.6) was significantly higher among participants with UC in T3 compared with T1 of UPF consumption ( P < 0.05). When adjusting for age, sex, disease type, and duration, number of episodes of active disease was lower in T1 compared with T3 (β = -7.11, P = 0.02); similarly, number of episodes of intestinal inflammation was lower in T1 (β = -0.95, P = 0.03). No significant differences were observed among participants with CD. UPF consumption may be a predictor of active symptomatic disease and inflammation among participants with UC. Reducing UPF consumption is a dietary strategy that can be suggested for minimizing symptoms and inflammation among people living with IBD.

CYTOKINE MULTI-OMICS AND MACHINE LEARNING IDENTIFY MIP1ALPHA AS A NOVEL MEDIATOR IN INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND Macrophage inflammatory protein 1 alpha (MIP1a) is a proinflammatory cytokine previously related to murine models of inflammatory bowel disease (IBD), but not definitively in the human disease. MIP1a acts as a chemoattractant of immune cells from the blood to the gut mucosa. We aimed to delineate the alterations to MIP1a and macrophages in relation to a range of IBD severity. HYPOTHESIS To characterize the changes to MIP1a production and localization in response to disease activity in IBD. APPROACH Both IBD (n=63) and control patients (n=118) were enrolled in this study (HSREB 6033229). Cytokine profiles were investigated using a 17-plex multi-fluorescent bead-based immunoassay (FirePlex, Abcam, Cambridge, UK) on serum from a subset of patients. Disease activity and macrophage levels were extracted from the clinical record. Activity was quantified using the Physician Global Assessment Score. Machine learning (ML) was performed with custom R scripts utilizing the tidymodels package (version 1.1) to determine the optimal model. Immunohistochemistry (IHC) was used to localize MIP1a in patient biopsies and quantified using QuPath software (v0.4). RESULTS An extreme gradient boost ML model was found to have optimal sensitivity and specificity for predicting disease activity based on serum cytokine levels. Within this model lower levels of serum MIP1a were associated with higher severity of IBD activity. However, in GI mucosal biopsies, the percentage of MIP1a positive cells in colon tissue increased with the severity of IBD. Macrophage concentrations in the peripheral blood were higher in patients on prednisone, and relatively similar across all other medications used in our cohort. CONCLUSIONS With the data collected, we identify MIP1a as a possible prognostic tool for quantifying IBD activity.

P368 Correlation between patient-reported outcome measures in inflammatory bowel disease and other measures of disease activity: a systematic review

Abstract Background The clinical activity of inflammatory bowel disease (IBD) has traditionally been evaluated by healthcare professionals. To allow direct reporting of symptoms by patients, several patient-reported outcome measures (PROMs) have been developed. We evaluated the correlation between IBD-specific PROMs and measures of endoscopic activity. Methods A systematic review of the literature was performed up to June 2022. Searches were conducted in three databases (PubMed, Scopus and Web of Science). The search protocol was registered in PROSPERO (CRD42022383899). Studies reporting the correlation between self-administered, IBD-specific PROMs and endoscopic scores were included. A descriptive analysis was performed by assessing the correlation between PROMs and IBD endoscopic activity. PROMs used in Crohn’s disease (CD) and ulcerative colitis (UC) were considered separately. Results Seventeen PROMs were identified encompassing a series of IBD signs and symptoms, mainly abdominal pain (n=10), stool frequency (n=6) and rectal bleeding (n=4). Twenty-two studies assessed correlations of PROMs with existing clinical measures of disease activity and/or their accuracy in predicting remission. The mainly used endoscopic indices were Simple Endoscopic Score for CD (SES-CD) and Mayo endoscopic subscore (MES) (n=11), and clinical indices were Harvey–Bradshaw Index for CD (n=7) and SCCAI for UC (n=7). Most studies used more than one comparator as standard for validation. A marked heterogeneity in the study design and statistical methods was observed. In CD, five studies analysed correlations between PROMs and SES-CD. They generally found weak correlations with PROMs (PRO2, n=2; mobile Health Index [mHI]-CD, n=1) (Figure), except for one which found a negative moderate correlation between PRO2 and SES-CD. The strongest correlation was with the stool frequency item of the Monitor IBD at home (MIAH) questionnaire. In UC, four studies assessed the correlation between PROMs and MES. Positive weak-to-moderate correlations were found with PRO2, MIAH rectal bleeding item and mHI-UC MES in four studies. Conclusion In CD, PROMs poorly correlate with endoscopic activity. However, in UC, rectal bleeding reasonably correlates with endoscopic status. It is well known that IBD symptoms overlap with those of other digestive diseases as functional disorders, especially in CD. In line with this, our data suggest that PROMs cannot substitute endoscopic data to monitor disease activity in IBD, especially in CD patients. Nonetheless, they represent a valuable complementary instrument to comprehensively describe disease control by capturing patient perspective. More studies are needed to better evaluate correlations between PROMs and clinical disease activity measures.

P713 The introduction of an intestinal ultrasound service significantly reduces diagnostic endoscopy usage in an Inflammatory Bowel Disease service – The SCOPELESS Study

Abstract Background Endoscopic assessment is the gold standard for monitoring of inflammatory bowel disease (IBD) activity. Intestinal ultrasound (IUS) is increasingly utilised as a non-invasive, alternative disease monitoring strategy. Our study aim was to quantify and compare endoscopy usage for evaluation of IBD disease activity before and after the introduction of an IUS service. Methods A retrospective single-centre study was performed. Total numbers of lower GI endoscopies (ileocolonoscopy or flexible sigmoidoscopy) performed for luminal Crohn’s disease (CD) or ulcerative colitis (UC) disease evaluation were collected across two 5-year time periods: the pre-IUS era (2010-2014) and the IUS era (2015-2019). Endoscopies for dysplasia surveillance were excluded. The primary endpoint was a comparison of the cumulative number of endoscopies for IBD disease activity evaluation annually relative to the annual number of patients seen in clinic in the pre-IUS and IUS eras. Secondary endpoints included evaluating the number of endoscopies by individual year within each time period, endoscopies according to diagnosis (CD vs. UC), and the number of IUS performed within the IUS era. Categorical variables were compared using a Chi-squared test. A p value &amp;lt;0.05 was considered statistically significant. Results The number of endoscopies performed for IBD disease evaluation decreased from 576 in the pre-IUS era to 474 in the IUS era despite an increase in cumulative annual patient reviews (1985 vs. 3337 patient reviews, respectively). The annual number of endoscopies for disease evaluation per patient in the pre-IUS and IUS eras is illustrated in Figure 1. The proportion of cumulative annual endoscopies relative to patients reviewed across the 5-years reduced from 29 per 100 patients in the pre-IUS era to 14 per 100 patients in the IUS era (OR 2.47, 95% CI 2.15-2.84; p &amp;lt; 0.001). There was a reduction in total endoscopies for CD evaluation from 325 to 264 and UC evaluation from 251 to 210. The proportion of endoscopies performed for CD vs. UC was unchanged between the two eras (56.4% vs. 55.7%; p = 0.81). In the IUS era, a total of 3319 IUS were performed (2673 CD, 646 UC). This included 1467 IUS for assessment of suspected activity (44 per 100 patients/year) and 1852 IUS for objective confirmation of clinical remission (55 per 100 patients/year). Conclusion In the 5 years following introduction of an IUS service, the number of endoscopies performed for evaluation of IBD activity per patient was halved. IUS was performed for both assessment of disease activity and objective confirmation of clinical remission. The potential workflow and cost savings of reduced endoscopies for IBD disease activity evaluation are significant.

P975 Monitoring Inflammatory Bowel Disease (IBD) by intestinal ultrasound decreases time to treatment change and time to remission in comparison to conventional management: Analysis of patients with IBD on multiple IBD therapies

Abstract Background Intestinal ultrasound (IUS) is a non-invasive, repeatable, and accurate disease monitoring modality that can provide real-time assessment of inflammatory bowel disease (IBD). We previously demonstrated that IUS shortens time to treatment change and time to remission in patients receiving upadacitinib and monitored by IUS compared to conventional management (ACG 2023). Here, we aim to assess the impact of IUS on management and outcomes of our pts with IBD receiving any IBD therapy. Methods We performed a retrospective analysis of patients who completed induction therapy (per individual drug label) but have active disease as measured by SCCAI &amp;gt;2 or HBI &amp;gt;4 between October 2021 and October 2023. We assessed for the time to treatment change (time from a positive clinical index to the time of a medical decision made), and time to clinical remission (time from a positive clinical index to the time of normalization (SCCAI ≤2, HBI ≤4 of the clinical index) and compared those between patients monitored by IUS and those managed with a conventional approach. Patients were matched by their provider and disease type. Active disease by faecal calprotectin (FCP) (FCP &amp;gt;150 mcg/g) and endoscopy (Mayo endoscopic score (MES) &amp;gt;0) were assessed ± a month before a positive clinical index was collected. An abnormal IUS was considered bowel wall thickness (BWT) &amp;gt;3 mm in the colon or terminal ileum and any hyperemia by colour Doppler signal (CDS) (modified Limberg score &amp;gt;0). Chi square analysis was performed, with p&amp;lt;0.10 significance. Results 54 patients (63 encounters) were included in this analysis (33 in the IUS cohort, 30 in the conventional management cohort) from 3 different providers. At inclusion, 9 (27%) pts in the IUS group and 10 (33.3%) in the conventional group had elevated FCP, and 5 (15.2%) pts in the IUS group and 29 (96%) had endoscopic disease. In the IUS group, the average time-to-treatment change was 2.2 (±1.2) days compared to conventional management 25.6 (±14.5), p=0.050. A total of 44 patients achieved clinical remission (22 IUS; 22 conventional management). The average time to remission in the IUS group was 128.1 days (±22.3) vs 230.6 (±38.2) days in the conventional management group, p=0.035). Drug class did not affect time to treatment change or time to remission (Table 1). The most significant reason for delay in the conventional group compared to the IUS group was awaiting endoscopy and FCP results. Conclusion Using IUS to assess disease activity in IBD is associated with earlier treatment changes and shorter time to remission compared to conventional approaches to disease monitoring, independent of therapy choice. Ongoing dissemination and incorporation of IUS in the management of IBD are warranted.

P454 Systemic free thiols associate with clinical and biochemical disease activity in Inflammatory Bowel Disease: a prospective diagnostic validation study

Abstract Background In the pathophysiology of inflammatory bowel diseases (IBD), oxidative stress plays an important role. Lower levels of plasma free thiols (FT) reflect a higher oxidative stress burden and correlate with IBD disease activity. However, their clinical significance as biomarker for disease activity remains unclear. This study aimed to prospectively validate the utility of plasma FT levels as biomarker for clinical, biochemical, and endoscopic disease activity in patients with IBD. Methods In an ongoing prospective diagnostic trial aiming to include 100 IBD patients, we conducted an interim analysis of plasma FT levels in 52 patients with IBD (24 Crohn's disease [CD], 21 ulcerative colitis [UC], and 7 patients with undetermined IBD). Clinical disease activity was quantified by the Harvey-Bradshaw Index (HBI) for CD and Simple Clinical Colitis Activity Index (SCCAI) for UC. Biochemical disease activity was determined by measuring blood C-reactive protein [CRP] and faecal calprotectin [fCal]). Endoscopic disease activity was quantified with the Mayo endoscopic subscore for UC and the Simple Endoscopic Score (SES-CD) for CD. Plasma FT levels were assessed for correlations with disease activity parameters using linear and logistic regressions models. Discriminative capacity of biomarkers was evaluated through calculating receiver operating characteristics (ROC) statistics. Results Plasma FT levels were significantly negatively correlated in clinical parameters, like HBI (r = -0.53, p &amp;lt; 0.05) (Fig. 1A). Other inflammatory biomarkers, like CRP, were also negatively correlated with plasma FT levels and were reduced in patients with active IBD (r = -0.43, p &amp;lt; 0.05) (Fig. 1B). Plasma FT levels accurately discriminated between CD patients with clinically quiescent (HBI &amp;lt; 5) and active disease (HBI ≥ 5) (AUC = 0.80, p = 0.02, Fig. 1C), better than fCal (AUC = 0.55, p = 0.83). Plasma FT were not significantly different for biochemically quiescent (CRP &amp;lt; 5 mg/l) and active (CRP ≥ 5mg/l) disease (AUC = 0.69, p = 0.20, Fig. 1D). Both Mayo and SES-CD scores, after adjusting for confounders, also exhibited a trend towards negative association with plasma FT levels (Fig. 1E). Figure 1 Conclusion Further completion of the trial will reveal whether systemic FT levels will reflect endoscopically observed disease activity, and this interim analysis shows strong correlations FT levels and parameters of clinically and biochemically active disease. Measuring systemic FTs in IBD may be a promising, minimally invasive strategy to monitor IBD disease activity. Funding None

P241 Systemic redox status associates with disease activity and clinical phenotypes in Inflammatory Bowel Disease

Abstract Background Oxidative stress is a key pathophysiological mechanism in inflammatory bowel diseases (IBD). Systemic levels of oxidative stress are reflected by reduced levels of free thiols (FT) in circulating proteins, especially those in albumin, which associates with disease activity in IBD. Yet, clinal value of circulating FT level as biomarkers of disease and therapy response remains largely unexplored. Here we investigated the association between plasma FT levels and clinical parameters, the plasma inflammatory proteome and medication use. Methods Plasma samples from 1,028 patients with IBD (567 Crohn's disease [CD] and 461 ulcerative colitis [UC]), and 500 healthy controls (HCs) participating in the 1000IBD and LifeLines projects were profiled for free thiols (FT), uric acid, bilirubin and 92 inflammation-related proteins (Olink Inflammation panelÒ). All biomarkers were associated with clinical phenotypes using general linear models adjusting for age, sex, body mass index, smoking and medication use. Results Plasma FT levels were significantly lower in IBD compared to HCs (p&amp;lt;0.05) (Figure 1A), with patients with UC showing even lower levels than patients with CD (p&amp;lt;0.05). Patients with UC on induction therapy had lower FT levels compared to patients on maintenance therapy (p&amp;lt;0.05). Furthermore, FT levels of patients with IBD were strongly associated with systemic inflammation (C-reactive protein [CRP], p&amp;lt;0.05) (Figure 1B). In both patients withCD and UC, reduced FT levels were associated with elevated levels of inflammation-, apoptosis-, and growth factor-related proteins, including C-X-C motif chemokine 9 (CXCL9) (Figure 1C-D), CUB domain-containing protein 1 (CDCP1) and caspase-8 (CASP8), proteins previous associated with preclinical IBD1-3. Furthermore, specifically for patients with UC, reduced FT levels were associated with elevated eotaxin-1 (CCL11) (Figure 1C), monocyte chemotactic protein-1 (MCP-1), and several cytokine biomarkers like Interleukine-6 (IL6) and Interleukin-17A (IL17A). Conclusion Systemic FT levels associate with inflammatory disease activity and clinical therapy and may offer potential utility in clinical assessments. This study highlights the intricate involvement of oxidative stress in various inflammatory pathways and components, particularly in innate/adaptive immune balance, cell damage, and apoptosis. These findings contribute to a deeper understanding of the interplay between oxidative stress, inflammation, and IBD. Funding: This study was supported by Janssen Research &amp; Development LLC.

P421 The faecal biomarker LDN-051 is a novel tool for monitoring disease activity and therapeutic response in Inflammatory Bowel Diseases

Abstract Background Crohn’s disease and ulcerative colitis, two forms of inflammatory bowel disease (IBD) require lifelong treatment and patient monitoring. Current predictors of relapse and therapeutic success have limitations, therefore there is high unmet need to identify novel biomarkers in IBD. Monitoring approaches for IBD are mostly invasive, time-consuming, and expensive. Therefore, a simple, rapid, and non-invasive test, with ability to differentiate IBD from other gastrointestinal conditions and to monitor disease activity, will have important clinical implications. Our previous mucosal cytokine profiling identified that Plasminogen activator inhibitor type 1 (PAI-1) is expressed in IBD patients with active disease, but not in control. Therefore, our aim was to assess the utility of PAI-1 in monitoring disease activity and therapeutic response of IBD patients in different biological samples. Methods Serum, biopsy and faecal samples were collected from 132 IBD patients and 30 controls without IBD. ELISA method was used to define the level of PAI-1 in the mucosa, serum, and faecal samples and the serum CRP levels were also determined. For the mucosal gene expression analysis qRT-PCR was used. The correlation and ROC analyses were applied to observe the relationship between the disease activity and PAI-1 level. Results The applied screening approach detected significant higher expression of PAI-1 in active IBD. We demonstrated that the serum, mucosal and faecal PAI-1 concentration was significantly elevated in IBD patients showing clinical and endoscopic activity. Additionally, in responder patients the initial PAI-1 level decreased significantly upon successful therapy, whereas it remained unchanged in non-responders. We also showed that faecal PAI-1 selectively increases in active IBD patients, but not in other organic gastrointestinal diseases. In addition, the stability analysis of faecal PAI-1 showed that the protein was detectable up to one week at room temperature and 4ºC. The serum, mucosal and faecal PAI-1 level showed positive correlation to the endoscopic activity. ROC curves demonstrated that faecal PAI-1 showed a relatively high power to distinguish between active and control patients. However, the serum CRP level no reflected to the therapeutic response. Conclusion Our results suggest that serum, mucosal and faecal PAI-1 expression reflects to the disease activity in IBD, which could be used to disease monitoring and possibly therapeutic response. The correlation between the faecal PAI-1 level and the endoscopic activity promotes that it could be used as a novel non-invasive disease specific faecal biomarker in the IBD diagnosis.

P824 Association between visceral adipose tissue and disease duration, clinical activity, and response to various biological agents in inflammatory bowel disease

Abstract Background The relationship between body fat composition and inflammatory bowel disease (IBD) progression, medical response, and prognosis is widely acknowledged. Visceral adipose tissue (VAT) has been shown to be profoundly responsible of most of the obesity-associated metabolic derangements, however it is also related to severity of inflammation. Although VAT can be estimated using computerized tomography, abdominal bioimpedance is a new and reliable technique without expense and radiation exposure. We investigated whether VAT is linked to the disease activity in severe IBD and the short-term response to biological therapies. Methods We prospectively evaluated 65 IBD patients, (n=26 with ulcerative colitis (UC) and n=39 with Crohn’s disease (CD) who had moderate-severe disease activity) at baseline before the initiation of biological therapy. We quantified VAT using abdominal bioimpedance (ViScan). VAT and other body fat metric measures (BMI, total and free fat mass, abdominal fat mass) were also analyzed. The response to biological agents was assessed by clinical (Mayo and CDAI) and endoscopical (mucosal healing) scores at 3 months. Results Out of the 65 patients, 22 individuals (33.8%) exhibited clinical and/or endoscopic response after 3 months. Among responders and non-responders, there was a comparable approximation of disease location (p=0.321) and behavior (p=0.239). Patients with CD had slightly lower levels of VAT, BMI, and free fat mass compared to those with UC. In non-responders with UC, VAT levels were lower than in responders, whereas in non-responders with CD, VAT levels were higher than in responders. No distinction was observed in the VAT response among other classes of biologics, including anti-TNF, ustekinumab, and vedolizumab. Conclusion In summary, VAT parameters using bioimpedance (ViScan) were found to be correlated with the disease activity and reliably identified IBD patients who responded well to various biological treatment in the short-term. Therefore, human fat indices might be novel biomarkers for disease severity and response to therapy.

P369 Altered fecal bile acid composition in active Ulcerative Colitis

Abstract Background A consistent finding in inflammatory bowel disease (IBD) is an altered composition of fecal bile acids, with an increase in primary bile acids and a decrease in secondary bile acids. It is less clear, whether fecal bile acids could prove to be biomarkers for IBD diagnosis and disease activity. The study aimed to determine correlations between eighteen fecal bile acid species and IBD entity as well as disease severity. Methods Eighteen fecal bile acid species were quantified from stool samples of 62 IBD patients and 17 controls using LC-MS/MS and stable isotope dilution. Bile acid levels were normalized to the dry weight of the fecal homogenates. For calculations, normalized bile acid concentrations and ratios of individual bile acid species to total bile acid levels were used. The p-values were corrected for multiple comparisons. Results In accordance with previous data, we showed that patients with IBD had more primary and less secondary bile acids in their stool compared to healthy controls, with greater differences when comparing healthy controls with ulcerative colitis (UC) than with Crohn´s disease (CD). In CD patients’ fecal calprotectin showed no correlations with any of the bile acids. In UC negative correlations between fecal calprotectin levels and two secondary bile acids, glycine conjugated lithocholic acid (GLCA) and hyodeoxycholic acid (HDCA), and thus total levels of secondary bile acids, existed. Comparing patients with low calprotectin levels (&amp;lt;50 µg/g) and patients with high calprotectin levels (&amp;gt;500 µg/g) in UC revealed that the latter group had lower GLCA and HDCA. Fecal bile acid levels of CD patients did not change with higher calprotectin. Moreover, serum C-reactive protein negatively correlated with the secondary bile acids HDCA, ursodeoxycholic acid, lithocholic acid, taurine conjugated lithocholic acid, deoxycholic acid and its taurine conjugated form in UC but not CD patients. Conclusion To distinguish between IBD subtypes, it may be helpful to note that impaired fecal bile acid homeostasis is specific to patients with active UC.