Endoscopic Disease Activity Research Articles

The urotensin-II receptor: A marker for staging and steroid outcome prediction in ulcerative colitis.

Urotensin-II receptor- (UTR) related pathway exerts a key-role in promoting inflammation. The aim was to assess the relationship between UTR expression and clinical, endoscopic and biochemical severity of ulcerative colitis (UC), exploring its predictivity of intravenous (iv) steroid administration therapeutic outcome. One-hundred patients with first diagnosis of UC and 44 healthy subjects were enrolled. UTR expression was assessed by qPCR, Western Blot (WB) and immunohistochemistry (IHC). Clinical, endoscopic and histological activity of UC were evaluated by using Truelove and Witts (T&W) severity index, Mayo Endoscopic Score (MES), and Truelove and Richards Index (TRI). The partial and full Mayo scores (PMS and FMS) were assessed to stage the disease. The UTR expression, resulted higher in the lesioned mucosa of UC patients in comparison to healthy subjects (p < .0001 all). Direct relationship between UTR (mRNA and protein) expression and disease severity assessment (T&W, PMS, MES and TRI) was highlighted (p < .0001 all). UTR expression resulted also higher in the 72 patients requiring iv steroids administration compared to those who underwent alternative medications, (p < .0001). The 32 steroid-non-responders showed an increased UTR expression (WB, IHC and qPCR from lesioned mucosa), compared to 40 steroid-responders (p: .0002, .0001, p < .0001 respectively). The predictive role of UTR expression (p < .05) on the negative iv steroids administration therapeutic outcome was highlighted and ROC curves identified the thresholds expressing the better predictive performance. UTR represents a promising inflammatory marker related to clinical, endoscopic, and histological disease activity as well as a predictive marker of steroid administration therapeutic outcome in the UC context.

Adalimumab Serum Concentrations, Clinical and Endoscopic Disease Activity in Crohn’s Disease: A Cross-Sectional Multicentric Latin American Study

Despite some variability in ideal serum Adalimumab (ADA) concentrations, there is increasing evidence that higher concentrations of anti-TNF-α agents can be associated with sustained efficacy, and low or undetectable levels may lead to loss of response. This study aims to correlate serum ADA concentrations with clinical and endoscopic activity in patients with Crohn's disease (CD). A cross-sectional and multicentric study was performed with patients with CD, who used ADA for at least 24 weeks. Patients were allocated into groups according to the presence of clinical or endoscopic disease activity. Serum ADA concentrations were measured and compared between groups. Overall, 89 patients were included. A total of 27 patients had clinically active CD and 62 were in clinical remission. Forty patients had endoscopic disease activity and 49 were in endoscopic remission. The mean serum ADA concentration was 10.2 μg/mL in patients with clinically active CD and 14.3 μg/mL in patients in clinical remission (p = 0.395). The mean serum ADA concentration in patients with endoscopic activity was 11.3 μg/mL as compared to 14.5 μg/mL in those with endoscopic remission (p = 0.566). There was no difference between serum ADA concentrations regarding clinical or endoscopic activity in CD, as compared to patients in remission.

P268 Development and validation of a novel composite index for the assessment of endoscopic and histologic disease activity in pouchitis: The Atlantic pouchitis index.

Abstract Background Several instruments have been used in clinical trials of pouchitis to define eligibility criteria and outcome measures but have not been formally validated. A need remains for a validated pouchitis instrument that is suitable for use in novel drug development. We developed and internally validated the novel composite Atlantic pouchitis index (API) for the assessment of endoscopic and histologic disease activity in patients with pouchitis. Methods Paired baseline and week 10 endoscopic videos and histologic images were obtained from 98 patients with chronic antibiotic-refractory pouchitis who participated in a randomised placebo-controlled trial of alicaforsen enema (ClinicalTrials.gov identifier: NCT02525523). For each pair, 4 endoscopists and 3 pathologists scored 59 items. These items included 51 component items from 11 indices (4 endoscopic, 4 histologic, 3 composite) identified in a prior systematic review and 8 additional items identified in a prior Research and Development/University of California Los Angeles appropriateness methodology exercise. The reliability of all measures was assessed using intraclass correlation coefficients (ICCs) and interpreted according to Landis and Koch benchmarks (slight, 0.00-0.20; fair, 0.21-0.40; moderate, 0.41-0.60; substantial, 0.61-0.80; almost perfect, 0.81-1.00). Responsiveness was evaluated using the area under the receiver operating characteristic curve (AUC). The API was developed using linear regression with a 100-mm visual analogue scale (VAS) of pouchitis activity as an anchor. Results Among all measures assessed for reliability and responsiveness, the simple endoscopic score for Crohn’s disease (SES-CD) and the Robarts histopathology index (RHI) were selected for inclusion in the API. The total API score ranges from 0 to 69, with higher scores indicating more severe disease activity, and can be calculated as API = (3 × SES-CD [0 to 12]) + (1 × RHI [0 to 33]). The API demonstrated almost perfect intra-rater reliability (ICC, 0.88 [95% CI: 0.81, 0.92]), substantial inter-rater reliability (ICC, 0.72 [95% CI: 0.60, 0.79]), and a high correlation with the VAS (r = 0.84 [95% CI: 0.76, 0.89]). Index responsiveness in detecting meaningful improvements in disease activity was higher for the API (AUC, 0.95 [95% CI: 0.89, 0.98]) than for existing endoscopic indices (∆AUC, 0.09-0.24; P≤0.005) (Table). Conclusion The novel API is a composite index of endoscopic (SES-CD) and histologic disease activity (RHI) that is reliable and significantly more responsive than existing endoscopic pouchitis scoring systems. The API is a promising tool for use in clinical trials of novel therapies for pouchitis. Further validation is needed in independent datasets.

P247 Oncostatin M and its receptor are markers of endoscopic and histological disease activity in Inflammatory Bowel Disease

Abstract Background Oncostatin M (OSM) and its receptor (OSMR) have been associated with active disease in patients with inflammatory bowel disease (IBD). This study compared the expression of OSM and OSMR in intestinal tissue according to clinical, endoscopic, and histological disease activity. Methods A multi-centre IBD database containing RNA-sequencing datasets, was used to analyse OSM and OSMR expression in ileal and/or colonic tissue, expressed as transcripts per million (TPM). Clinical scoring systems included the Harvey Bradshaw Index for Crohn’s disease (CD) and partial Mayo score for ulcerative colitis (UC). Endoscopic scoring systems included the simple endoscopic score for CD (SES-CD) and UC endoscopic index of severity (UCEIS). Histological scoring included the modified Naini and Cortina, and Riley scores. Graphs were presented in log transformed TPM+1 values. Results 155 patients (108 CD, 47 UC) and 38 controls were included. For IBD patients, 49% were men, median age was 35 years and intestinal tissue was collected at endoscopy (73%) and surgery (27%). Compared to controls, patients with CD and UC had significantly elevated median expression of OSM (0.08, 0.29 and 0.34 TPM respectively) and OSMR (1.21, 1.69 and 3.53 TPM respectively). OSMR expression was higher in UC patients than CD (p&amp;lt;0.001). There was no difference in OSM or OSMR between Harvey Bradshaw Index categories (0-4 vs 5-7 vs 8-16) or partial Mayo scores (0 vs 1-3 vs 4-7). Endoscopically, OSM was higher for SES-CD scores of 16-51 (1.11 TPM), compared to SES-CD scores of 0-3 (0.14 TPM, p=0.003) and controls (0.08 TPM, p&amp;lt;0.0001). Median OSMR increased non-significantly with increasing SES-CD scores (score 0-3: 1.59 TPM; score 4-15: 1.90 TPM; score 16-51: 2.04 TPM). There was no difference in OSM and OSMR expression between UCEIS scores, but the most severe disease (UCEIS score 5-8) had higher expression than controls for both OSM (3.92 vs 0.08 TPM, p&amp;lt;0.001) and OSMR (6.10 vs 1.21 TPM, p&amp;lt;0.0001). Increasing expression of OSM and OSMR was found with increasing histological scores, see Figure. Using the modified Naini and Cortina score for CD, OSM and OSMR were most expressed in the highest scores compared to the lowest scores (OSM: 1.48 vs 0.09 TPM, p&amp;lt;0.001; OSMR: 5.50 vs 1.27 TPM, p=0.003). For the modified Riley score for UC, both OSM and OSMR were also able to differentiate between the highest and lowest score groups (OSM: 3.14 vs 0.12 TPM, p=0.0001; OSMR: 6.61 vs 1.58 TPM, p&amp;lt;0.0001). Conclusion This study showed that OSM and OSMR expression in intestinal tissue is associated with inflammation both histologically and endoscopically. Further investigations are needed to confirm our observations and explore the OSM pathway’s relevance in intestinal inflammation.

P177 C-reactive protein/albumin ratio: a novel biomarker for monitoring of the disease activity in Ulcerative Colitis patients

Abstract Background Fecal calprotectin (FC) is a reliable laboratory test for non-invasive assessment of disease activity in ulcerative colitis (UC) patients; it's high cost, absence of widespread availability and low patient adherence limits it's use as a potential surrogate for endoscopy. The association of higher C-reactive protein (CRP) and low albumin levels, both obtained from patient's sera, with disease acitivity in UC, is well established. C-reactive protein/albumin ratio (CAR) is suggested as a biomarker for evaluating disease activity in various inflammatory conditions. We aimed to evaluate association between CAR, FC, CRP and serum albumin values with disease activity in UC patients. Methods A single center, noninterventional retrospective chart review of adult UC patients treated with biologics at a tertiary center was performed. Routine clinical (stool frequency score – SFS, and rectal bleeding score – RBS), biochemical (CRP, serum albumin, FC), and endoscopic (Mayo Endoscopic Subscore – MES) findings were assessed prior to initiating biologics. Active UC was defined as SFS 2/3 + RBS 2/3 + MES 2/3. Differences between continuous variables were calculated using independent sample t-tests and Mann–Whitney U test. Sperman’s correlation and ROC curve analysis were carried out. The Z statistic was used to compare correlation coefficients and AUC. Results Total of 82 patients (52.2% females, mean age 40.3 ± 15.3 years, smokers 16.9%) with dominantly extensive UC (57.3%) were analysed. The CAR (0.175 vs 0.025; p=0.02) and FC (1363.5 vs 65.5; p=0.01) levels were significantly higher in active vs inactive UC patients. Positive correlation was observed between CAR (rs = 0.354, p = 0.01), FC (rs = 0.448, p = 0.001) and CRP (rs = 0.316, p = 0.005) with active UC. Although serum albumin (r's = - 0.093, p = 0.532) negatively correlated with disease activity it didn't reach statistical significance. There was no statistically significant difference between CAR and FC correlation coefficients. The area under the curve (AUC) for the diagnosis of active UC was 0.896 (SE: 0.058; 95% CI 0.73 - 0,983, p=0.015) and 0.994 (SE: 0.009; 95% CI 0.98 - 1, p=0.001) for CAR and FC, respectively. Although AUC for FC was higher compared to CAR it didn’t reach statistical significance (p = 0.1). The cut-off value associated with the active UC for CAR was 0.06 (sensitivity 77,2%, specificity 100%), and 120 mcg/g for FC (sensitivity 97.6%, specificity 100%). Conclusion There is good correlation between CAR and clinical as well as endoscopic disease activity in patients with UC, comparable to FC. CAR could be offered as a cheap and practical biomarker for detection of active UC disease.

P408 Dual therapy with vedolizumab and tofacitinib in refractory ulcerative colitis patients – single centre experience

Abstract Background Despite significant impact biological treatment had on prospects of patients with ulcerative colitis, there is still a substantial proportion of patients with non-response to multiple drugs. Beside dose optimization and selection of agents with different mechanism of action, combination of two different targeted molecules has recently been proposed in cases where inflammatory activity cannot get under control. This case series provide promising results of vedolizumab in combination with tofacitinib in treatment resistent UC patients. Methods Patients with complicated refractory or acute severe colitis, in whom combined treatment with vedolizumab and tofacitinib based on shared clinical decision was started, were included. Data on demographics, treatment details, persistence and disease activity including laboratory markers, clinical activity index (partial Mayo score) during regular visits every 2 months up to one year after treatment initiation were collected. Currently available data were analyzed at 6 months. Endoscopic disease activity before and 2-6 months after dual therapy start was evaluated. Results In total, 21 UC patients who were started on vedolizumab and tofacitinib dual therapy between Oct 2020 and Sep 2022 were included. Tofacitinib dose was 10mg bid in all patients and all patients on vedolizumab maintenance treatment had intensified dosing regimen. Mean patients age was 36.4±8.1 years, 47.6% were males and 52.4% females. Mean disease duration at baseline was 7.5±5.8 years. All patients had advanced disease including 61.9% with extensive colitis and 38.1% with left-sided colitis. At least 2 previous biologics in monotherapy were used in 85.7% of patients. Mean pMayo score at baseline was 5.6±1.9 and decreased to 0.5±0.9 at 6 months (p=0.0020). Initial fecal calprotectin in the cohort was 1829±2520µg/g vs. 225±257µg/g at 6 months (p=0.0068) and mean CRP changed from 11.4±17.1 to 5.4±7.2mg/l (p=ns). Endoscopic Mayo score before dual treatment initiation averaged 2.8±0.5 indicating mostly severe disease activity and decreased to 1.4±1.2 during follow-up endoscopy (p=0.0005) with half of the patients having only no to mild activity (eMayo 0-1). Up to now, dual therapy had to be terminated in 7 patients – 4 patients failed on the treatment, 1 refused to continue with dual therapy, 1 patient experienced adverse event (liver lesion) and 1 was discontinued for reimbursement reasons. Conclusion In the presented small cohort of patients with refractory ulcerative colitis, in whom other modalities were depleted or colectomy was considered, combined vedolizumab and tofacitinib treatment has proven to be efficient with half of the patients reaching mucosal healing after 6 months and without raising significant safety concerns.

P183 Development of a new simple ultrasound activity score for intestinal Behçet's Disease

Abstract Background Intestinal Behçet's disease (BD) is a relapsing-remitting disease typically associated with punched-out ulcers in the ileocecal region. Optimal monitoring of disease activity is necessary; however, ileocolonoscopy cannot be performed on a regular basis as it is invasive, resource-intensive and causes considerable patient discomfort. Furthermore, there are risks of intestinal bleeding and perforation caused by pretreatment laxatives and air insufflation during the examination. Hence, other follow-up examinations are required. Intestinal ultrasonography (IUS) is a minimally invasive imaging method, but there are no previous reports of comparisons between IUS and endoscopy for intestinal BD. This study aimed to evaluate the usefulness of IUS in assessing the activity of ileocecal ulcers in intestinal BD. Methods This retrospective single-centre study included patients with intestinal BD who underwent colonoscopy and IUS within 2 weeks, from 2007 to 2020. Correlations between the corresponding endoscopic activity using the Sakita–Miwa classification and six IUS variables (bowel wall thickness [BWT], vascularity, bowel wall stratification, intramural and extramural abscesses, fistulas and mesenteric lymphadenopathy) were assessed and used to select the variables that should be included in the new simple score. IUS findings were also compared with biomarker (C-reactive protein [CRP]) concentrations and clinical severity indices (Crohn’s disease activity index and disease activity index for intestinal BD [DAIBD]). Results Seventy-nine IUS examinations from 53 patients were included. Univariate analysis revealed that CRP and DAIBD and the IUS findings BWT, vascularity and bowel wall stratification and intramural and extramural abscesses differed significantly according to endoscopic ulcer activity. Multivariate analysis using a logistic regression model revealed that only BWT and vascularity were statistically different; therefore, a new simple score ([2*BWT] + [5*vascularity]) was constructed. Receiver operating characteristic curve analysis revealed an area under the curve of 0.91 for detecting endoscopic activity, which was superior to those of CRP (0.80; P=0.069), Crohn’s disease activity index (0.69; P=0.002) and DAIBD (0.67; P&amp;lt;0.001). Conclusion A new simple ultrasound activity index for intestinal BD comprising BWT and vascularity was constructed and correlated well with endoscopic disease activity. This is the first report describing the usefulness of IUS for intestinal BD, and we believe the findings will have many implications in clinical practice.

DOP04 Single cell RNA sequencing reveals a potential role for IFNγ in priming circulating monocytes for intestinal inflammatory function in Crohn’s Disease.

Abstract Background Hyper-inflammatory monocyte-derived cells accumulate in the intestine and contribute to pathology in inflammatory bowel disease (IBD). Our previous work has shown that intestinal monocyte-derived cells from Crohn’s Disease patients have a reduced response to the immunoregulatory cytokine IL-10 and that this property is already established in circulating monocytes prior to their arrival in the intestine. Here, we have used scRNAseq and functional experiments to define the scope of IBD-associated changes in blood monocytes and explore the role of inflammatory cytokines in shaping these. Methods Total monocytes were isolated from the peripheral blood of 12 newly diagnosed, treatment naive IBD patients with active endoscopic disease (6 Crohn’s Disease [CD] and 6 Ulcerative Colitis [UC]) and 10 healthy controls (HC) by negative magnetic selection. scRNAseq was performed using the 10x Genomics Chromium 3’ assay at a target capture rate of 1000 cells/sample and sequencing at ~50,000 reads/cell. Data were analysed using Cell Ranger, Seurat, Metascape and Gene Set Enrichment Analysis. Blood CD14+ monocytes from healthy donors were pre-incubated in medium alone or with IFNγ (100U/ml) for 24 hours. Inhibition of LPS-induced TNFα production by IL-10 was measured by intracellular cytokine staining and flow cytometry. Results UMAP clustering identified six transcriptionally distinct monocyte clusters: clusters 0, 1 and 2 mapped to classical monocytes; cluster 3 to non-classical monocytes; cluster 4 to intermediate monocytes; and cluster 5 contained platelet signals. The proportion of cluster 4 was increased in CD patients compared to HC. Differential gene expression analysis of CD and UC monocyte clusters compared to healthy controls identified a total of 246 differentially expressed genes (DEGs) in CD and 149 in UC. Only 39 of these DEGs were significantly affected in both diseases. Both CD and UC DEGs were significantly enriched for pathways related to cytokine signalling and inflammation (Figure 1). IFNγ and TNFα -response gene sets were positively enriched in CD, but negatively enriched in UC (Figure 2). Pre-treatment of healthy monocytes with IFNγ in vitro reduced their response to IL-10 as measured by inhibition of LPS-induced TNFα (Figure 3). Conclusion Expression of genes associated with inflammation and cytokine signaling are altered in blood monocytes from IBD patients implying their modification by systemic signals prior to arrival in the intestinal mucosa. Cytokine- (IFNγ and TNFα) stimulated genes are differentially affected in CD and UC monocytes. In CD, systemic IFNγ may reduce the responsiveness of monocytes to IL-10 to prime them for inflammatory function.

P112 S1PR expression on circulating immune cells is not limited to lymphocytes in patients with inflammatory bowel disease

Abstract Background With the recent approval of ozanimod in ulcerative colitis (UC) and promising data of etrasimod, S1P receptor (S1PR) modulators are entering the therapeutic landscape. Besides differences in receptor selectivity (ozanimod S1PR1/5, etrasimod S1PR1/4/5), both compounds induce a drop in circulating B/T-lymphocytes, without affecting monocyte counts. This lymphocyte drop seems independent of treatment response, suggesting that other cell types – like monocytes, implicated in IBD pathogenesis - might contribute to efficacy. Furthermore, very little is known about the expression of S1PR on circulating lymphocytes/monocytes in the context of IBD. Methods Peripheral blood mononuclear cells were isolated from 135 IBD patients with active endoscopic disease (Table 1), and subsequently FACS sorted (CD14 monocytes and CD4 T-cells). RNA was extracted from lysed cells, and single-end sequenced using Illumina HiSeq4000. Results All S1PR were identified on both CD4 T-cells and monocytes, though with hardly any S1PR5 expression on circulating monocytes and hardly any S1PR3 expression on T-cells. Receptor expression on both monocytes and T-cells correlated significantly only for S1PR1 (r0.25, p=0.003) and S1PR4 (r 0.19, p=0.02). Circulating T-cells had substantial higher expression of S1PR1 (fold change [FC] 1092.0, p&amp;lt;2.2E-16), S1PR2 (FC 1.84, p=5.3E-7), S1PR4 (p=2.4, p&amp;lt;2.2E-16) and S1PR5 (FC infinite, p&amp;lt;2.2E-16) compared to monocytes. In contrast, circulating monocytes expressed significantly more S1PR3 (FC infinite, p&amp;lt;2.2E-16). Receptor expression on T-cells did not differ between patients with Crohn’s disease (CD) and UC, whereas monocyte S1PR1 was significantly elevated in CD as compared to UC (FC 4.5, p=0.006) (Figure 1). Previous anti-TNF was not associated with any difference in S1PR1, but was associated with a slight increase in S1PR4 (FC=1.26, p=0.02). No association was observed in relation to previous vedolizumab exposure, whereas concomitant steroid use was linked to a decrease in S1PR5 on T-cells (FC 0.35, p=0.007). Disease duration or inflammatory burden (CRP) were not associated with any S1PR, though S1PR1 positively correlated with age in T-cells (r 0.23, p=0.008). In UC, S1PR1 on monocytes was significantly elevated in proctitis compared to left-sided and pancolitis (p=0.02); in CD, L1 disease was linked to elevated S1PR1 monocyte expression as compared to patients with L2/L3 (p=0.002). No link with CD disease behaviour could be demonstrated. Conclusion Besides lymphocytes, monocytes do express S1PR in patients with IBD. The clinical consequences and the potential link with efficacy of S1PR modulators should therefore be further explored, especially given the heterogeneity of S1PR expression on circulating cells in IBD patients.

P235 Patients with inflammatory ileal pouch anal anastomosis (IPAA) disorders are characterized by a distinct breath volatile organic compounds (VOC) metabolome profile

Abstract Background Following creation of an IPAA in patients with ulcerative colitis (UC), more than 60% of subjects develop inflammatory complications. The current objective assessment for inflammation of the pouch is limited to surrogate stool and blood biomarkers or endoscopy. The development of non-invasive and accurate biomarkers for the assessment of IPAA inflammation is an area of unmet need. Measurement of exhaled breath volatile organic metabolome compounds (VOCs) has shown promise as a biomarker for the diagnosis and monitoring of inflammatory disorders. We here aimed to characterize the pattern of VOCs in the exhaled breath of patients with an IPAA and assess whether VOC analysis is able to discriminate patients with endoscopically active IPAA inflammation from patients without IPAA inflammation. Methods This is a cross-sectional study of patients with an IPAA created for the management of UC. Exhaled breath samples were collected at time of endoscopic evaluation of the pouch and 97 VOC metabolites assessed via selective ion flow tube mass spectrometry (SIFT-MS). The IPAA cohort was dichotomized using the endoscopic pouch disease activity index (PDAI) into endoscopic PDAI of &amp;gt;= 4 (severe inflammation), or endoscopic PDAI score &amp;lt;= 1 (mild or no inflammation). Principle component analysis (PCA) was conducted to reveal the VOCs with the strongest discriminatory capability and principle component regression (PCR) was performed to assess the association of exhaled breath VOC analysis in differentiating the groups. Results Exhaled breath metabolome analysis was performed on 10 subjects with PDAI &amp;gt;=4 and 7 subjects with PDAI &amp;lt;=1. Demographics are provided in Table 1. PCA indicated robust discrimination of the two groups based on breath VOCs (Figure 1). 10 out of 97 VOCs were up-regulated in the PDAI &amp;gt;=4 group compared to control, including ammonia and hydrogen sulfide. Isopropenyltoluene, tetrachloroethylene, and 3-pentanone provided the highest contribution to differentiate between the cohorts (Figure 2). Receiver operative curve (ROC) analysis of the PCR model indicated an area under the curve (AUC) of 0.81 (0.61-99), suggesting a strong association of breath VOCs with inflammation of the pouch (Figure 1). Conclusion VOC exhaled breath metabolome analysis shows a strong ability to discriminate patients with severe endoscopic pouch inflammation from patients with minimal to no endoscopic inflammation. The differences in reported VOCs point toward metabolic differences in bacterial fermentation, lipid and carbohydrate metabolism, and an increase in reactive oxygen species in patients with endoscopic pouch inflammation. Validation studies addressing the role of VOC analysis for non-invasive disease assessment patients with IPAA are ongoing.

P178 Evaluation of the Ulcerative Colitis Intestinal Ultrasound (UC-IUS) Index in Pediatric patients with newly diagnosed ulcerative colitis

Abstract Background Transabdominal bowel ultrasound (TABUS) is a non-invasive tool that can be used to assess bowel inflammation in ulcerative colitis (UC). It is particularly attractive for use in children, given the need for general anesthesia when undergoing endoscopic assessment of bowel inflammation. A standardized TABUS scoring system in UC has only been developed in adults (the UC Intestinal Ultrasound (UC-IUS) Index). Our aim was to evaluate the UC-IUS Index in Pediatric patients. Methods Pediatric patients (&amp;lt;18 years old) with suspected UC were prospectively enrolled. TABUS was performed for the right side colon, transverse, descending, and sigmoid colons. UC-IUS Index scores were calculated: bowel wall thickness (BWT) (&amp;gt;2mm=1, &amp;gt;3mm=2, &amp;gt;4mm=3), Doppler signal (spots=1, stretches=2), haustrations (abnormal=1), and fat wrapping (present=1). Mayo endoscopic subscore (for each segment), Pediatric Ulcerative Colitis Activity Index (PUCAI), and inflammatory biomarkers were collected. Non-parametric tests were used to correlate UC-IUS and BWT with Mayo endoscopic subscores. Receiver operating characteristic (ROC) analyses evaluated the UC-IUS Index BWT cut-offs. Results Fifty-two patients (56% male) were included (Table 1). Data for 206 colonic segments were analyzed (2 segments missing due to 1 incomplete colonoscopy). Total UC-IUS scores significantly correlated with CRP (rho=0.61), albumin (rho=-0.49), PUCAI (rho=0.54), FCP (rho=0.41). UC-IUS Index scores and mean BWT for each segment showed significant moderate correlations with Mayo sub-scores of that segment (rho=0.60 and rho=0.58, respectively) (p&amp;lt;0.001) (Fig 1). These correlations were strong in the right colon (rho=0.77, rho=0.69), and moderate in the transverse (rho=0.52, rho=0.56), descending (rho=0.43, rho=0.50), and sigmoid (rho=0.50, rho=0.46) colons (p&amp;lt;0.01). The adult UC-IUS 2mm cut-off (Mayo 0 vs. Mayo 1-3) performed similarly in our Pediatric patients (sensitivity 80%, specificity 96%, area under the curve (AUC) 0.92). The 3mm (Mayo 0-1 vs. Mayo 2-3) and 4mm (Mayo 0-2 vs. Mayo 3) cut-offs had lower sensitivity (sensitivity 44%, specificity 98%, AUC 0.87; sensitivity 59%, specificity 92%, AUC 0.80) (Fig 2). Thinner BWT cut-offs performed better: 2.5mm (sensitivity 65%; specificity 89%) and 3.5mm (sensitivity 71%; specificity 86%). Fig 1: Fig 2: Conclusion In Pediatric patients with newly diagnosed UC, TABUS was a useful tool, with the UC-IUS and BWT correlating well with their endoscopic, clinical, and biochemical disease activity. Compared to the adult UC-IUS Index, Pediatric patients need a thinner BWT cut-off to better discriminate between mild vs. moderate/severe disease (2.5mm instead of 3mm) and mild/moderate vs. severe disease (3.5mm instead of 4mm).

P250 The impact of Primary Sclerosing Cholangitis (PSC) on fecal calprotectin assessment in individuals with Inflammatory Bowel Disease (IBD)

Abstract Background Fecal calprotectin (FCP) is recommended as a non-invasive biomarker in ulcerative colitis (UC); however, the accuracy of FCP in individuals with concurrent primary sclerosing cholangitis (PSC) is less understood due to biliary fluid calprotectin excretion in PSC. We aimed to determine the relationship of endoscopic disease activity to FCP levels in individuals with PSC and colitis (PSC-IBD) compared to individuals with UC alone. Methods Individuals with PSC-IBD and UC controls who underwent colonoscopy at a large tertiary academic medical center. Controls with similar UC extent were selected in a 2:1 ratio. Mayo endoscopic scores (MES) were derived from the endoscopic database. If no prospective score was recorded, images were reviewed by two investigators with adjudicated discrepancies. Disease characteristics, baseline demographics, FCP (within 6 months of endoscopy), and C-reactive protein (CRP) were derived from the electronic medical record. Exclusion criteria included Crohn's disease or non-IBD colitis, infectious colitis, treatment change between endoscopy and FCP measurement, and colonic resection. Mean FCPs and standard deviations (SDs) were calculated, stratified by PSC status and MES. Multivariable linear regression was employed to assess the association of PSC on FCP adjusting for MES, age, alkaline phosphatase (ALP), and disease location. Results 264 colonoscopies for 197 patients (mean age 48, 61% males, 97% extensive disease) were identified with corresponding FCP from 2013 to 2022. Compared to UC controls, there were more males in the PSC-IBD cohort; MES did not differ significantly between the two groups (Table 1). There was no significant difference in mean FCP in PSC-IBD compared to UC controls (314.7 vs 284.5, p=0.56). Mean FCP increased with increasing MES (Table 2). There was no significant difference in mean FCP between those with PSC and those without when stratified by MES (Table 3). In multivariable linear regression, left-sided disease extent, MES, and ALP were independently associated with increasing FCP (Table 4). Conclusion In this cohort, a diagnosis of PSC was not associated with significant differences in FCP for IBD patients when stratified by MES. These data suggest that FCP remains a reliable marker of colitis activity in IBD patients with and without PSC. Further research is required to understand the role of PSC activity in modulating FCP concentrations.

P245 The Relationship Between the Endoscopic Healing Index and Magnetic Resonance Enterography In Crohn’s Disease Patients

Abstract Background The endoscopic healing index (EHI) is a serum biomarker panel that identifies endoscopic Crohn’s Disease (CD) activity. Endoscopy and biomarkers are limited in assessing small bowel disease compared to magnetic resonance enterography (MRE). The Simplified Magnetic Resonance Index of Activity (MaRIAs) is validated to detect CD activity. Data are lacking on the relationship between EHI with other endpoints. This study performed the first assessment of EHI to diagnose CD-related intestinal inflammation on MRE using the MaRIAs score. Methods Data were extracted on CD patients with EHI within 90 days of MRE. We assessed the diagnostic accuracy of EHI for any (MaRIAs≥1) or severe (MaRIAs≥2) MR inflammation identified on MRE using area under the receiver operator characteristic (AUROC) curve analyses. Proportions with inflammation on MRE were compared between groups above and below the identified EHI and FCAL threshold. Analyses were repeated between EHI and active endoscopy (SES-CD≥5), fecal calprotectin (FCAL&amp;gt;50, &amp;gt;250), and clinical symptoms (CD PRO-2≥8). Results 241 MREs uniquely paired to either EHI or FCAL from 155 patients, mean age was 42 years, 50.3% were female, 83.2% of patients had small bowel involvement, and 29.7% had penetrating disease. The mean time between EHI to MRE was 28 days, and the mean time between FCAL and MRE was 24 days. Both EHI and FCAL had similar accuracy to diagnose inflammation (AUROC: EHI:0.635-0.651, FCAL:0.680-0.708). Optimal EHI values were 42 and 26 for inflammation on MRE and endoscopy, respectively. Patients with EHI≥42 (100% vs. 63%, p=0.002), FCAL&amp;gt;50µg/g (87% vs. 64%, p&amp;lt;0.001) and FCAL&amp;gt;250µg/g (90% vs. 75%, p=0.02) had higher rates of MaRIAs≥1 compared to lower values. EHI differentiated ileitis more than FCAL (delta: 24-25% vs. 11-21%). Patients with low FCAL had high rates (59-69%) of active endoscopic disease, whereas those with low EHI rarely (6%) with endoscopic activity. Patients with FCAL≥50µg/g had higher rates of severe inflammation compared to FCAL&amp;lt;50µg/g (75% vs. 47%, p&amp;lt;0.001) whereas smaller differentiation existed for EHI. In patients with CD PRO-2 scores, clinical remission was not associated with disease activity corresponding to active EHI, endoscopy, or MRE. Conclusion In CD patients predominantly with ileal involvement, EHI&amp;gt;42 and FCAL&amp;gt;50 were both specific to confirm inflammation on MRE. Lower EHI values (&amp;lt;42), but not low FCAL (&amp;lt;50), were associated with lower rates of severe radiologic inflammation. MRE inflammation was frequently present in the presence of low EHI and FCAL with similar proportions of false negative MRE results. However, the absence of endoscopic inflammation was only associated with low EHI, but not low FCAL values.

EFFICIENCY OF DUAL THERAPY WITH VEDOLIZUMAB AND TOFACITINIB IN REFRACTORY ULCERATIVE COLITIS PATIENTS – SINGLE CENTRE EXPERIENCE

Abstract INTRODUCTION Despite significant impact biological treatment had on prospects of patients with ulcerative colitis, there is still a substantial proportion of patients with either secondary loss of response or primary non-response to multiple drugs. Beside dose optimization and selection of drugs with different mechanism of action, combination of two different targeted molecules has been proposed in cases where inflammatory activity cannot get under control. This case series provide promising results of vedolizumab in combination with tofacitinib in treatment resistent UC patients. METHODS Patients with complicated refractory or acute severe colitis, in whom combined treatment with vedolizumab and tofacitinib based on shared clinical decision was started, were included. Data on demographics, treatment details, persistence and disease activity including laboratory markers, clinical activity index (partial Mayo score) during regular visits every 2 months up to one year after treatment initiation were collected. Currently available data were analyzed at 6 months of treatment. Endoscopic disease activity before and 2-6 months after dual therapy start was evaluated. RESULTS In total, 21 ulcerative colitis patients who were started on vedolizumab and tofacitinib dual therapy between October 2020 and September 2022 were included. Tofacitinib dose was 10mg bid in all patients and all patients on vedolizumab maintenance treatment had intensified dosing regimen. Mean patients age was 36.4±8.1 years, 47.6% were males and 52.4% females. Mean disease duration at baseline was 7.5±5.8 years. All patients had advanced disease including 61.9% with extensive colitis and 38.1% with left-sided colitis. At least 2 previous biologics in monotherapy were used in 85.7% of patients. Mean pMayo score at baseline was 5.6±1.9 and decreased to 0.5±0.9 at 6 months (p=0.0020). Initial fecal calprotectin in the cohort was 1829±2520µg/g vs. 225±257µg/g at 6 months (p=0.0068) and mean CRP changed from 11.4±17.1 to 5.4±7.2mg/l (p=ns). Endoscopic Mayo score before dual treatment initiation averaged 2.8±0.5 indicating mostly severe disease activity and decreased to 1.4±1.2 during follow-up endoscopy (p=0.0005) with half of the patients having only no to mild activity (eMayo 0-1). Up to now, dual therapy had to be terminated in 7 patients – 4 patients failed on the treatment, 1 refused to continue with dual therapy, 1 patient experienced adverse event (liver lesion) and 1 was discontinued for reimbursement reasons. CONCLUSION In the presented small cohort of patients, however, with refractory and complicated ulcerative colitis in whom other modalities were depleted or colectomy was considered, combined vedolizumab and tofacitinib treatment has proven to be very efficient with half of the patients reaching mucosal healing after 6 months and without raising significant safety concerns.

THE RELATIONSHIP BETWEEN SELF-REPORTED SLEEP, WRIST ACTIGRAPHY, AND SYMPTOMS AMONG ADULTS WITH INFLAMMATORY BOWEL DISEASE (IBD)

Abstract BACKGROUND Recently, there has been a growing recognition of the bidirectional link between sleep and inflammation. Several studies have reported the prevalence of sleep disturbances in those with Inflammatory Bowel Disease (IBD) and found poor sleep has the potential to increase the risk of disease relapse. Additionally, sleep loss may adversely affect cognitive performance, mental health, metabolism, and pain perception. While previous research has indicated potential associations between sleep and symptoms commonly reported in IBD, few studies use objective measures of sleep. Wrist actigraphy can objectively and non-invasively measure sleep-wake cycles and has been found feasible for use in the IBD population. This study aimed to examine the relationship between self-reported sleep, wrist actigraphy, and symptoms among adults with IBD. METHODS Participants with IBD (ages 18-55) completed demographic and sleep questionnaires, a 28-day symptom diary, and wore a wrist actigraph for up to 15 days. Sleep questionnaires were the Pittsburgh Sleep Quality Index (PSQI), Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance, and PROMIS sleep-related impairment. Participants rated symptoms on a 4-point Likert scale, including gastrointestinal-related symptoms such as abdominal pain, diarrhea, bloating, constipation, fatigue, and extraintestinal symptoms, including anxiety, depression, and stress. Data analysis included descriptive statistics and Pearson correlations. RESULTS Twenty-five participants (Crohn’s Disease=18; Ulcerative Colitis=7) were included. The mean age was 33.5 (SD 8.3) years of age, 60% were female, 92% were White, 88% were non-Hispanic or Latino, and 36% had active endoscopic disease. Most (64%) participants had poor quality sleep (PSQI global ≥ 5). In contrast, the averages for onset latency, efficiency, wake after sleep onset (WASO), and total sleep time were all within normal values at 17.4 min (SD 26.7), 84.2% (SD 7.5), 48.7 min (SD 27.3), and 435.8 min (69.2), respectively. PROMIS sleep disturbance was significantly correlated with abdominal pain (r=0.56), bloating (r=0.43), constipation (r=0.46), fatigue (r=0.50), and stress (r=0.42). PROMIS sleep-related impairment was significantly correlated with bloating (r=0.47), constipation (r=0.50), fatigue (r=0.60), depression (r=0.42), and stress (r=0.46). Onset latency was significantly correlated with anxiety (r=0.41) and stress (r=0.42). Sleep time was significantly correlated with fatigue (r=0.42). CONCLUSION This study highlights sleep disturbances are prevalent in those with IBD and significantly correlated with both GI and extraintestinal symptoms. Future work is needed to explore these relationships further and the potential benefit of sleep interventions in this population.

MULTIPLE ENVIRONMENTAL AND SOCIAL DETERMINANTS OF HEALTH FACTORS WERE NOT ASSOCIATED WITH THE GASTROINTESTINAL SYMPTOMATIC BURDEN OF ULCERATIVE COLITIS WITH MUCOSAL HEALING

Abstract INTRODUCTION In a biopsychosocial interdisciplinary model, complex interactions between the hosts (individuals/patients), disease (e.g., ulcerative colitis [UC]), and environment (e.g., social determinants of health [SDOH]) may all contribute to the disease burden. Whether SDOH contributes to the symptomatic burden of UC in deep remission is unclear. METHODS We performed a secondary analysis on prospectively collected data from adults with UC enrolled in the biobank at a tertiary referral center in southern California from 2014-2021. Standardized clinical (unweighted two-item patient-reported outcome [PRO-2] for stool frequency [SF] and rectal bleeding [RB]; remission=SF0/RB0), endoscopic (Ulcerative Colitis Endoscopic Index of Severity [UCEIS]; remission UCEIS=0), and histologic (Geboes score; remission &amp;lt;2B.0) disease activity assessments were performed within 30 days of a colonoscopy (case) with segmental colonic biopsies. SDOH were assessed using the California Healthy Places Index (SDOH Index), a publicly available zip code-based system that ranks SDOH domain and subdomain scores from the least to most healthy (0-100 percentile) using weighted z-scores. Patients without SDOH scores (e.g., reside outside of California; n=88 cases) were excluded. We used χ2-square and Wilcoxon-Mann Whitney tests to investigate for associations between SDOH factors (non-parametric, independent variables dichotomized as below vs above the median) and cardinal GI symptoms (continuous unweighted PRO-2 symptomatic severity and dichotomized clinical remission/active disease), patient-, and disease-related factors. In adults with UC in endoscopic or endo-histologic remission, we used univariate logistic regression to assess the risk of health disadvantage (SDOH score below median) and the presence of GI symptoms. RESULTS Of the 166 UC cases, 46% (76/166), 38% (63/166), and 30% (49/166) were in clinical, endoscopic, and endo-histologic remission, respectively. Approximately one-fifth of cases (21%, 35/166) had SDOH scores below the state median. However, health disadvantage (below SDOH index median) was not associated with clinical, endoscopic, or endo-histologic disease activity; and neither were IBD duration; gender or race/ethnicity (all p&amp;gt;0.05) (Tab 1). Approximately one-third of cases had active GI symptoms despite endoscopic (32%, 20/63) and endo-histologic remission (29%, 14/49). However, none of the eight investigated SDOH domains were associated with increased risks for GI symptoms when UC had objective mucosal healing on colonoscopy (Tab 2) CONCLUSION Although one-third of adults with mucosal healing of UC report GI symptoms (diarrhea/rectal bleeding), there was no association with multiple social determinants of health factors (e.g., education, neighborhood, economic, social, and environmental) in this secondary analysis of a prospective cohort.

Development of a Novel Ulcerative Colitis Endoscopic Mayo Score Prediction Model Using Machine Learning.

Endoscopic assessment is a co-primary end point in inflammatory bowel disease registration trials, yet it is subject to inter- and intraobserver variability. We present an original machine learning approach to Endoscopic Mayo Score (eMS) prediction in ulcerative colitis and report the model's performance in differentiating key levels of endoscopic disease activity on full-length procedure videos. Seven hundred ninety-three full-length videos with centrally-read eMS were obtained from 249 patients with ulcerative colitis, who participated in a phase II trial evaluating mirikizumab (NCT02589665). A video annotation approach was established to extract mucosal features and associated eMS classification labels from each video to be used as inputs for model training. The primary objective of the model was a categorical prediction of inactive vs active endoscopic disease evaluated against 2 independent test sets: a full set with a baseline single human expert read and a consensus subset in which 2 human reads agreed. On the full test set of 147 videos, the model predicted inactive vs active endoscopic disease via the eMS with an area under the curve of 89%, accuracy of 84%, positive predictive value of 80%, and negative predictive value of 85%. In the consensus test set of 94 videos, the model predicted inactive vs active endoscopic disease with an area under the curve of 92%, accuracy of 89%, positive predictive value of 87%, and negative predictive value of 90%. We have demonstrated that this machine learning model supervised by mucosal features and eMS video annotations accurately differentiates key levels of endoscopic disease activity.

Polysubstance use in inflammatory bowel disease is associated with increased risk of emergency department visits: a longitudinal study.

Polysubstance use (PSU), the simultaneous use of 2 or more substances of abuse, is common in inflammatory bowel disease (IBD). Preliminary studies suggest it may be associated with poor outcomes. This prospective study evaluated the impact of PSU on disease activity and healthcare resource utilization in IBD. This study was conducted in a tertiary IBD center between October 29, 2015, and December 31, 2019. Participants were assessed over 2 time points (index and follow-up outpatient appointments) separated by a minimum of 6 months. Demographics, endoscopic disease activity, and surveys assessing symptoms, healthcare resource utilization and substance use (tobacco, alcohol, marijuana, cocaine, methamphetamine, heroin, opioid, or benzodiazepine) were abstracted. We identified PSU during the index appointment and computed descriptive statistics and contingency table analyses, and multivariate logistic regression models at follow up to evaluate outcomes. 162 consecutively enrolled IBD patients were included. Seventy-five patients (46%) were polysubstance users at the index appointment. The most common cohorts were utilizing tobacco and alcohol (n=40) or tobacco and opioids (n=13). On bivariate and multivariate analyses, PSU during the index visit was positively associated with emergency department (ED) visits (odds ratio [OR] 2.51, 95% confidence interval [CI] 1.24-5.07; P=0.01) and negatively associated with extraintestinal manifestations (OR 0.37, 95%CI 0.18-0.74; P=0.005). Age, sex, disease activity, disease subtype and IBD-related symptoms were not associated with PSU. IBD patients exhibiting PSU had increased risk of future ED visits. This study highlights the risks of PSU and reinforces the importance of appropriate substance use screening.

Application of deep learning in the diagnosis and evaluation of ulcerative colitis disease severity.

Achieving endoscopic and histological remission is a critical treatment objective in ulcerative colitis (UC). Nevertheless, interobserver variability can significantly impact overall assessment performance. We aimed to develop a deep learning algorithm for the real-time and objective evaluation of endoscopic disease activity and prediction of histological remission in UC. This is a retrospective diagnostic study. Two convolutional neural network (CNN) models were constructed and trained using 12,257 endoscopic images and biopsy results sourced from 1124 UC patients who underwent colonoscopy at a single center from January 2018 to December 2022. Mayo Endoscopy Subscore (MES) and UC Endoscopic Index of Severity Score (UCEIS) assessments were conducted by two experienced and independent reviewers. Model performance was evaluated in terms of accuracy, sensitivity, and positive predictive value. The output of the CNN models was also compared with the corresponding histological results to assess histological remission prediction performance. The MES-CNN model achieved 97.04% accuracy in diagnosing endoscopic remission of UC, while the MES-CNN and UCEIS-CNN models achieved 90.15% and 85.29% accuracy, respectively, in evaluating endoscopic severity of UC. For predicting histological remission, the CNN models achieved accuracy and kappa values of 91.28% and 0.826, respectively, attaining higher accuracy than human endoscopists (87.69%). The proposed artificial intelligence model, based on MES and UCEIS evaluations from expert gastroenterologists, offered precise assessment of inflammation in UC endoscopic images and reliably predicted histological remission.

Common laboratory blood test immune panel markers are useful for grading ulcerative colitis endoscopic severity

BackgroundAt present, many indicators reflect the clinical disease activity of ulcerative colitis (UC). However, commonly used inflammatory markers do not show good utility for indicating endoscopic disease activity. The purpose of this study was to evaluate high sensitivity C-reactive protein (hs-CRP), C-reactive protein to albumin ratio (CAR), inflammatory markers, and complete blood count (CBC) related parameters in patients with UC as simple, non-invasive, and independent markers of endoscopic activity (EA).MethodsWe retrospectively collected extensive data from the hospital medical records of 386 patients who presented with UC to the First Affiliated Hospital of Xinjiang Medical University (Urumqi, China) from 2018 to 2022 January. The Mayo endoscopic score (MES) was used to evaluate endoscopic disease activity. All included patients were defined as the MES-All group; those with extensive colitis (E3) were defined as the MES-E3 group. Demographics, laboratory parameters, endoscopic results, the extent of disease, and drug history were recorded and analyzed.ResultsFor patients in the MES-All or MES-E3 group, hs-CRP, CAR, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) were significantly higher in EA UC patients than in those with mucosal healing. The mean platelet volume (MPV) and lymphocyte to monocyte ratio were significantly lower in active disease than in the patient’s remission (p < 0.001). ROC analysis showed that in the MES-All and MES-E3 groups, the cutoff values of hs-CRP activity under endoscopy were 5.32 mg/L (AUC 0.850, sensitivity 77.6%, specificity 81.9%) and 5.16 mg/L (AUC 0.902, sensitivity 86.9%, specificity 85.4%) respectively, and the cutoff values of CAR were 0.14 (AUC 0.853, sensitivity 76.8%, specificity 84.8%) and 0.18 (AUC 0.904, sensitivity 81.8%, specificity 89.6%) respectively. Multivariate logistic regression analysis showed that hs-CRP, CAR, NLR, and PLR identified UC EA, while decreased MPV reflected inflammatory activity in the UC mucosa.ConclusionEspecially in patients with extensive colitis, hs-CRP and CAR are closely related to EA and show a higher diagnostic value compared to the related CBC parameters. The aforementioned indicators are simple and non-invasive independent markers that reflect the EA in UC.