Active Colitis Research Articles

P1175 Abdominal Pain is Associated with Poor Quality of Life in Quiescent Inflammatory Bowel Disease: A Cross-sectional Study of the SPARC Inflammatory Bowel Disease Cohort

Abstract Background Abdominal pain (AP) is common in patients with active inflammatory bowel disease (IBD) and has been associated with poor quality of life (QOL). Despite greater therapeutic options, symptoms persist in a subset of patients. Data is lacking regarding AP in patients with objectively documented quiescent disease. Among endoscopic quiescent disease: (1) estimate prevalence of AP, (2) assess predictors of worse AP, (3) describe its impact on validated QOL measures. Methods This cross-sectional study used prospectively collected data from SPARC (Study of a Prospective Adult Research Cohort) IBD, a multicenter longitudinal study of well-phenotyped adult IBD patients initiated by the Crohn’s & Colitis Foundation in 2016. Quiescent IBD was defined as Mayo endoscopy score <2 for ulcerative colitis (UC) and SES-CD score <3 for Crohn’s disease (CD). Patient reported outcomes (PROs) within 30 days of endoscopy were analyzed. Patients with ostomy or IPAA were excluded. Self-reported AP was categorized as none, mild, or moderate/severe. Univariate statistics used Pearson’s Chi-square and Kruskal-Wallis tests. Results A total of 973 patients with quiescent IBD (606 CD; 367 UC) were included in the study (Table 1). AP was more commonly reported in quiescent CD (31.2% mild, 15.5% moderate/severe) as compared to quiescent UC (23.4% mild, 10.1% moderate/severe) (p<0.001). In the entire quiescent cohort, those with mild or moderate/severe AP were more likely to be female sex (63.1% mild; 67.4% moderate/severe; p<0.001), higher BMI (28.4 mild; 30.0 moderate/severe; p=0.008) and have more recent tobacco use (p=0.004). Ileocolonic involvement was more commonly seen in moderate/severe AP. Mild and moderate/severe AP was associated with subjective fecal urgency, stool frequency, and bloody stool (all p<0.001). Disease behavior in CD was not associated with abdominal pain. General well-being was poorer for those with more severe AP (p<0.001), though this did not appear to result in more frequent recent ED visits or hospitalizations. Figure 1 depicts the PROMIS responses. Overall, worse AP was associated with universal worse scores on all PROMIS measures and subscales (all p<0.001). Data suggested that more severe AP had the greatest impacts on the "Fatigue" subscale. Conclusion In this study of patients in SPARC IBD with endoscopic quiescent IBD the overall prevalence of AP was 41.7% overall and more commonly reported in CD as compared to UC. AP was associated with a greater prevalence of other symptoms, worse general well-being, and poorer quality of life across all measures. Further research is needed to elucidate the pathophysiology for presence of AP in quiescent IBD and develop personalized management approaches.

P422 Prevalence of poor sleep quality assessed by wrist actigraphy and sleep questionnaire in Inflammatory Bowel Disease patients and its association with disease activity and quality of life

Abstract Background An association between active inflammatory bowel disease (IBD) and poor sleep quality has been proposed, however studies evaluating both subjective and objective assessment of disease activity and sleep quality are limited. Our study aimed to investigate the prevalence of poor sleep quality assessed by wrist actigraphy and sleep questionnaires in IBD patients and its association with disease activity and quality of life. Methods A prospective observational study was conducted in Siriraj Hospital, Mahidol University, Bangkok, Thailand from March 2021 to December 2022. Eligible IBD patients were categorized into remission, mild, and moderate-to-severe groups, based on standard clinical disease activity scores. Demographic data, inflammatory markers, inflammatory bowel disease questionnaire (IBDQ), sleep questionnaire (Pittsburgh Sleep Quality Index, PSQI), and seven-day sleep data from wrist actigraphy (Actiwatch®, CamNtech, Cambridge, United Kingdom) were obtained. The prevalence of sleep disorder and group comparison were analyzed. Results Eighty-four participants (40 Crohn’s disease, 44 UC), consisting of 60 remission, 16 mild, and 8 moderate-to-severe disease activity, were enrolled. Baseline demographic data were comparable between each group. Lower hemoglobin and albumin levels, and higher serum C-reactive protein, and fecal calprotectin levels were found in the more clinically active groups (table1). Fifty patients (60%) had poor sleep defined by PSQI > 5 with a trend to be higher in the group with active symptoms (57% in remission, 63% in mild, and 75% in moderate-to-severe group, p=0.31). Using actigraphy, the group with moderate-to-severe symptoms tended to have longer sleep latency, more frequently awake after sleep, and poorer sleep efficiency than the other groups (Figure 1). Patients with more severe disease activity had poorer quality of life with a mean IBDQ of 190 in remission, 159 in mild, and 134 in moderate-to-severe group (p<0.001). Conclusion Poor sleep quality is common among IBD patients, even those with clinical remission. Those with more severe symptoms had poorer sleep quality and worse quality of life. Sleep assessment and treatment should be integrated into IBD standard clinical care.

P1228 The EISER Study: Identifying Microbial Factors Associated with Subclinical Gut Inflammation in Psoriatic Arthritis Patients Who Develop Inflammatory Bowel Disease

Abstract Background Nearly 8% of patients with spondyloarthritis (SpA) manifest symptoms that are compatible with active inflammatory bowel disease (IBD). It is well established that microbial dysbiosis is associated with different immune-mediated diseases. We therefore hypothesized that the gut microbiome could be a modulator of intestinal inflammation and factor in the pathogenesis of IBD in SpA patients. Methods As part of the EISER study, we selected a subset of 193 subjects diagnosed with psoriatic arthritis (PsA), a form of SpA, who had no prior diagnosis of IBD. The presence of subclinical symptoms compatible with IBD was evaluated at time of enrollment. For patients with fCAL levels of 80 µg/g or higher, colonoscopy was performed and histological analysis of biopsies collected during the procedure were used to diagnose IBD. Capsule endoscopy was performed on those patients with a negative colonoscopy result. Stool samples were collected from all participants, and microbial DNA was extracted for shotgun metagenomic sequencing using the Illumina HiSeq platform. Sequenced data was processed using MetaPhlAn 4 to estimate taxonomic composition, MMEDS for overall microbiome analysis, and R for additional statistical analyses. Results Twenty-five out of 193 subjects in our cohort (12.95%) had symptoms that were compatible with subclinical IBD (sIBD) and five patients (2.6% of total) were confirmed to have clinical IBD (cIBD). The use of nonsteroidal anti-inflammatory drugs (NSAIDs) resulted in significant differences in overall alpha (Shannon entropy, p=0.03) and beta microbial diversity (PERMANOVA, p=0.043), while the use of proton-pump inhibitors (PPI) resulted in significant differences in beta diversity (PERMANOVA, p= 0.036). Patients with cIBD had significantly higher abundance of taxa including Prevotella copri and Prevotella stercorea. P. copri, P. stercorea and fCAL were all significantly elevated in cIBD patients (Wilcoxon’s p=0.0278, 0.0007, 0.0161), although with a larger effect size in P. copri and P. stercorea (Cohen’s D: P. copri = 1.074; P. stercorea = 1.269; fCAL= 0.629). fCAL was also significantly elevated in patients who used PPIs (p= 4.456e-11), while P. copri and P. stercorea abundances were not impacted (Wilcoxon’s p: P. copri = 0.2394; P. stercorea = 0.0643). Conclusion Microbiome composition was impacted by the use of NSAIDs and PPI. We identified taxa differentially enriched in cIBD patients, including Prevotella copri and P. stercorea. Importantly, while fCAL was significantly higher in cIBD patients, its discriminatory power was not as strong as that of P. copri and P. stercorea, suggesting that these taxa could be potentially used as biomarkers of co-morbid IBD in patients with PsA.

P1161 Prevalence of undernutrition in patients with inflammatory bowel disease and improvement after nutritional advice

Abstract Background The prevalence of undernutrition ranges from 25% to 70% and severe undernutrition from 1% to 30% among individuals with active inflammatory bowel disease (IBD). The aetiology of malnutrition is multifactorial. There are not many studies that have assessed nutrition after therapy modification and dietary advice. Aim To study the prevalence of undernutrition in IBD and the change after nutritional advice. Methods In this single-centre prospective cohort study, 218 consecutive patients with IBD were screened. Patients with associated diseases that could lead to undernutrition were excluded (N=18). Nutritional assessment was done as per the European Society for Clinical Nutrition and Metabolism (ESPEN) definition: BMI <18.5 kg/m2 or unintentional weight loss >10% were defined as undernutrition and the Malnutrition Inflammation Risk Tool (MIRT) score was calculated. Obesity was defined as per the WHO Asian BMI classification: grade 1 (BMI 25-29.9 Kg/m2) and obesity grade 2 (BMI >30 Kg/m2)1. Patients were given nutritional advice and therapy was optimized as per disease activity. BMI and MIRT were calculated on subsequent visits to assess response to nutritional advice. Results Of 200 patients (median age 39 [IQR 28-53] years; 96 females), 105 had ulcerative colitis (UC), 93 Crohn’s disease (CD), and 2 IBD-unclassified. Fifty-four (27%) patients had undernutrition (28 UC, 25 CD, and 1 IBD-U). Sixty-one (30.5%) patients were obese. At follow up (median duration 24 months), of 37/54 patients with BMI <18.5 Kg/m2, BMI increased in 24 (64.8%) and decreased in 13 (35.1%); of 17 patients with >10% unintentional weight loss, 5 (29.4%) had increased weight on follow-up. MIRT score decreased in 24/54 patients (44.4%), remained same in 14 (25.9%), and increased in 16 patients (29.6%). Of the 24 patients with decrease in MIRT score, 7/24 (29.1%) received only dietary advice, 10 (41.6%) received dietary advice and optimization of IBD treatment, and 7 (29.1%) received only optimization of IBD treatment. Conclusion The prevalence of undernutrition and obesity in patients with IBD was 27% and 30.5%, respectively. After dietary advice and therapy optimization, nutrition improved in 53.7% while MIRT score decreased in 43.3% of patients.

P694 Age is a strong of predictive risk factor for anti-TNF therapy related adverse events in IBD patients

Abstract Background Anti-TNFα is the first class of biologics approved for treatment of moderate-to-severely active Inflammatory Bowel Disease (IBD). More than two decades on, anti-TNFs remain one of the most commonly used biologics for both Ulcerative Colitis (UC) and Crohn’s Disease (CD), and often as first-line therapy. Although effective, they cause several adverse events (AEs), sometimes requiring withdrawal of therapy. We aimed to record AEs and understand factors that could predict risk of AEs. Methods All IBD patients exposed to anti-TNF therapy were identified from EMR at two centres of a large tertiary hospital between January 2009 and June 2022. All relevant demographic and clinical data were collected for those patients with well recorded AEs and follow-up. Data on cumulative AEs directly attributed to anti-TNFs that ranged from mild reactions to serious AEs (defined as those requiring review/withdrawal of anti-TNF), were collected. Adverse events (AEs) were recorded as per relevant systems involved e.g.- haematological, cardiac etc., including infections and malignancies as separate categories. All analysis (normalization, hypothesis testing, and visual reports were performed using R software package Version: R 4.2.1. Results A total of 844 IBD patients (Male =408) were included with an age range of 18-75yrs. Majority were Caucasian in ethnicity (514) and more patients with CD [605(71%)] were exposed to anti-TNF than UC. The age profiling analysis was performed across ethnic groups (Asian, Caucasian and Others). Age associated AE was reported across all the groups (data not shown). It must be mentioned that though not significant, Caucasian patients were more susceptible towards AE as compared to Asian. Conclusion · Patient age above 50yrs has a strong predictive risk factor for AEs related to anti-TNF therapy for IBD. · In our cohort, more than half of patients >50yrs reported at least one AE in UC, and the age was lower in CD. · Although Caucasians were more vulnerable to AEs, this was not statistically significant. · Clinicians should consider and discuss this risk before selecting patients for anti-TNF therapy. · With multiple biologic choices currently available, another class could be considered where possible, for the >50yr patient cohort.

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 <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 < 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.

OP15 High-definition white light endoscopy with segmental re-inspection is non-inferior compared to dye-based chromoendoscopy in Inflammatory Bowel Disease: the randomized controlled HELIOS trial

Abstract Background Patients with colonic inflammatory bowel disease (IBD) undergo endoscopic surveillance to detect and remove colorectal neoplasia (CRN). Although high-definition dye-based chromo-endoscopy (HD-CE) is the recommended modality in guidelines, high-definition white light endoscopy (HD-WLE) with matched procedural time may yield similar neoplasia detection rates. We designed a non-blinded, randomized controlled trial in four academic hospitals aiming to compare three endoscopic surveillance techniques in IBD patients for the outcome of CRN detection rate. Methods Eligible patients were aged ≥18 years and scheduled for colitis-associated CRN surveillance according to Dutch IBD surveillance guidelines. Patients were excluded in case of insufficient bowel cleansing, active colitis, or if >50% of the colon was resected. Patients were randomly assigned (2:2:1) to undergo HD-WLE with segmental re-inspection (SR), HD-CE, or single pass HD-WLE. The primary outcome was CRN detection rate, defined as the proportion of procedures in which macroscopic CRN was detected. Secondary outcomes included the number of CRN and withdrawal time. To demonstrate non-inferiority of HD-WLE with SR compared to HD-CE (one-sided testing, α=0.05, 1−β=0.8, non-inferiority (NI) margin -10%), and superiority compared to single-pass HD-WLE (two-sided testing, estimated CRN detection rate of 24% and 12%, respectively1) with Mantel-Haenszel analyses, a total of 566 patients were needed. Results In total, 666 patients were randomized, 563 fulfilled all study criteria and were analysed per protocol (table 1). Of these, 51.8% were male, with a median age of 51 years (interquartile range 35-63). CRN detection rates were 9.8% for HD-WLE with SR, 13.1% for HD-CE, and 6.1% for single pass HD-WLE. HD-WLE with SR was non-inferior compared to HD-CE (Δ-3.1%, lower boundary of the 95% confidence interval (CI) -8.1 not exceeding the NI margin of -10%, p<.05). HD-WLE with SR was not superior compared to single-pass HD-WLE (Δ3.7%, 95% CI -2.5:9.1%, p=0.31). A significant difference was found between arms for the number of detected CRN (n=29 vs n=36 vs n=8 for HD-WLE with SR, HD-CE and single-pass HD-WLE, respectively (p=.04)) and withdrawal time (p=.03, table 1). One advanced lesion was detected (high-grade dysplasia in the HD-CE arm). Conclusion In this large, randomized controlled trial, HD-WLE with SR was non-inferior compared to HD-CE for CRN detection in IBD patients. HD-WLE with SR was not superior to single-pass HD-WLE, although this may have resulted from lower than expected neoplasia yields and subsequent lower power. These results suggest that HD-WLE with SR may provide a feasible alternative to HD-CE in clinical practice (NCT04291976). 1Imperatore et al. JCC 2019;13(6):714-24

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.

P1141 Global perspectives on managing Inflammatory Bowel Disease (IBD) during pregnancy and lactation: current state and the necessity for enhancements

Abstract Background Reproduction is an essential part of life. Our aim was to obtain a global perspective on IBD management by gastroenterologists (GIs) during preconception, pregnancy, lactation and neonatal period. Methods An anonymous survey (75 questions) was developed to investigate different aspects of clinical practice concerning the management of pregnancy and breastfeeding in patients with IBD. A national representative from each European country, USA, Latin America, Australia and New Zealand was selected to distribute the survey among their GI colleagues who treat patients with IBD (irrespectively of their experience). Results A total of 856 GIs from 36 countries participated in the survey. Among the participants, 63% had over a decade of experience as GIs, and 61% identified themselves as IBD specialist (IBDologists). The most relevant survey results and sub-analyses based on expertise are presented in tables 1 and 2. In the management of pregnant patients in remission, treatment discontinuation occurred either consistently or occasionally as follows: 20% thiopurines, 37% vedolizumab, 31% ustekinumab, and 96% small molecules. Notably, 13% did not always discontinue small molecules in patients contemplating pregnancy. Safety was the main reason for discontinuing IBD therapy during pregnancy. Contrary to the recommendations in clinical practice guidelines, many GIs avoid starting oral or rectal budesonide, anti-TNF, vedolizumab or ustekinumab during a disease flare. Further, a third of GIs would start thiopurines for a flare during pregnancy. Moreover, 13% will never perform a colonoscopy in a pregnant patient to guide decision making. Half of GIs implemented a dedicated outpatient follow-up program for pregnant patients in remission, with 87% enrolling all pregnant patients in this program. Concerning breastfeeding, 14% believed that all drugs can be used while breastfeeding. Regarding offspring’s vaccination, about 20% recommend against the administration of non-live vaccines and only 50% recommended avoiding live vaccines during the first 12 months for children exposed to anti-TNF in-utero. Among those GIs who recommended delaying vaccines in such cases, only 41% recommended testing the infant for detectable anti-TNF levels if live vaccines were required. Among the surveyed GIs, only a minority had a referral obstetrician, and only 35% referred patients with active or complicated IBD, while 45% had a referral paediatrician with expertise in IBD. Conclusion The management of IBD during pregnancy, lactation, and neonatal period is notably suboptimal, even among GIs specifically dedicated to IBD. It is crucial to address this current need and implement urgent educational measures in this area.

DOP80 Prevalence and factors associated with Inflammatory Bowel Disease (IBD) activity during pregnancy: updated data from the DUMBO Registry

Abstract Background IBD remission is key for pregnancy outcomes. Previous studies have suggested a disease recurrence risk of approximately 30% in patients in remission at conception, but this could be influenced by disease control in the periconceptional period and the discontinuation of treatments for IBD during pregnancy. Aim To provide updated data on the incidence of disease relapse during pregnancy in IBD patients and to identify predictive factors of relapse. Methods Pregnant patients with IBD from DUMBO registry were included. DUMBO is a prospective, observational, and multicentre registry, endorsed by GETECCU which enrols pregnant women with IBD over 5 years in 70 centres in Spain. Study protocol is summarized in figure 1a. Relapse was defined based on the Crohn’s Disease Activity Index and the Partial Mayo Score in Crohn’s disease (CD) and ulcerative colitis (UC), respectively. Only patients in clinical remission at conception were considered for the relapse risk analysis (Cox-regression analysis). Only serious adverse events (SAE) were recorded. Results 1,033 patients were available in DUMBO registry, 57 (5.5%) had active disease at conception. 830 patients had given birth (98% singleton), 69 had early termination (48 of them miscarriages), and 134 pregnancies were still ongoing. The probability of having active disease at each trimester was higher in patients with active disease at conception (table 1a). Seven patients underwent surgery due to IBD during pregnancy (3 abdominal and 4 perianal surgery); all of them were in remission at conception. The proportion of patients with severe infections during pregnancy was higher in patients with active disease during pregnancy (2.8% vs. 0.8%, p<0.05); there were no differences in other SAE based on the activity. 73 out of 976 patients in remission at conception relapsed throughout pregnancy or puerperium (figure 1b, table 1b). The proportion of patients who withdrew treatment during pregnancy, excepting mesalamine, was similar between relapsers and non-relapsers (table 1c). To have UC vs. CD (Hazard ratio=3, 95% confidence interval=1.8-5.3) was the only variable associated with the risk of relapse. Conclusion The risk of having active disease during pregnancy was higher in patients with activity at conception. The risk of relapse in patients in remission at conception was lower than previously described. The risk of relapse was 3-fold higher in UC than in CD. Since most relapses occur from the second trimester of gestation onwards, and serious complications (including surgery) can occur also in patients in remission at conception, monitoring IBD during this period should be closely conducted.

P436 The AI based Red Density score is correlated with the established and new histological indices for Ulcerative Colitis in an independent cohort

Abstract Background Red Density (RD) is an automated endoscopic tool that is developed for the objective evaluation of disease activity in ulcerative colitis (UC). The initial development integrated histological disease activity based on Robarts histological index (RHI) in the machine learning algorithm. New histological scores for UC have been developed since. The aim of this study was to establish the correlation between RD and the Nancy histological index (NHI) and PICaSSO Histologic Remission Index (PHRI). Methods Patients included in 4 centers in the ongoing PROCEED-UC study (NCT04408703) had assessment with RD in the rectum and sigmoid at baseline, w52 or early termination visit. Biopsies were taken according to protocol. Biopsies were scored for the Geboes score (GBS), RHI, NHI, PHRI in a blinded way after initial scoring convention training. Correlation was tested on patient level between mean RD per segment and the different histological indices based on Spearman correlation. Results In total 96 patients from 4 centers were included representing 2634 RD images from 400 colonic segments with biopsies and corresponding RD score. Mean (± SEM) rectal RD score was 32.7 (± 4.54), 33.69 (± 5.25) and 64.86 (± 31.71) at baseline, w52 and ET respectively. Mean sigmoidal RD score was 38.13 (± 3.68), 42.82 (± 11.80) and 77.33 (± 24.65) at baseline, w52 and ET respectively. Analysis based on the segment with the highest mean RD score per patient showed significant correlation with NHI (r=0.60, p<0.0001), PHRI (r=0.62, p<0.0001). In the rectum the RD score at all time points correlated significant with NHI (r =0,53, p<0.0001) and PHRI (r=0.63, p<0.0001). Similar correlation was seen in the sigmoid for NHI (r=0.51, p<0.0001) and PHRI (r=0.22, p0.0108). A RD score of <57.5 (Likelihood Ratio (LR) 4.176; AUC 0.7820 (95CI 0.7047 - 0.8593), p<0.0001) was associated with histological remission based on NHI (<2) and a RD score of < 64.5 (LR 9.821; AUC 0.8133 (95%CI 0.7053 - 0.9212), p<0.0001) with histological remission based on PHRI (=0). The current dataset demonstrated to be stable in line with the previously established RD cut-off with GBS and RHI. 1 Conclusion In an independent cohort of patients with UC the correlation with the established and new histological indices for UC is confirmed. This underlines the value of RD as an objective endoscopic tool for the assessment of histological and endoscopic disease activity in UC. Ref 1: Bossuyt P, Nakase H, Vermeire S, De G, Eelbode T, Ferrante M, et al. Automatic, computer-aided determination of endoscopic and histological inflammation in patients with mild to moderate ulcerative colitis based on red density. Gut. 2020;69:1778–86.

P472 A Real World Practice of Intestinal Ultrasound in the Monitoring of Disease Activity in Ulcerative Colitis

Abstract Background Intestinal ultrasound (IUS) has emerged as an important monitoring tool in the clinical course of ulcerative colitis (UC). Previously known factors about UC have been considered in terms of the associations with IUS. However, a few studies reported about the associations between the findings of IUS and clinical factors. Methods We performed a multi-center, cross-sectional study of patients with UC who received IUS and clinical exams including endoscopy simultaneously. The primary endpoint was the association between endoscopic disease activity as Mayo endoscopic score (MES) and IUS finding as Milan ultrasound criteria (MUC). The secondary endpoint comprised the various clinical factors associated with MUC. Patients with MUC<6.2 were defined as low MUC group and others as high MUC group. Results A total of 35 patients were enrolled in this study. The numbers of Low- and high-MUC groups were 23 and 12, respectively. The median age in each group was 41 and 53 years old. The portion of male sex in each group was 57% and 75%. There were no significant differences in terms of body mass index, onset age, disease duration, current medication such as 5-aminosalicylic acid, steroid, immunomodulator, and biologics and small molecules between both groups. Compared with low and high MUC groups, endoscopic remission was more significantly associated with the low MUC group than the high MUC group (35% vs. 0, p = 0.032). In addition, the rate of disease activity ranged from remission to mild, as tolerable clinical activity, was also significantly higher in the low MUC group than the high MUC group (91% vs. 58%, p = 0.033). Other outcomes such as symptomatic remission, histologic remission, and biochemical response revealed similar rates between the two groups. Conclusion Low MUC of IUS in the patients with UC showed significant clinical association such as endoscopic remission and tolerable clinical activity. This study is now ongoing prospective research and further investigation into the relationship between IUS and clinical outcomes of UC will elicit robust results.

P336 Exploring Extracellular Matrix Markers in Ulcerative Colitis: Degradation and Formation Insights

Abstract Background The gold standard for assessing disease activity in ulcerative colitis (UC) is endoscopy, which is uncomfortable for the patient, and only evaluates the superficial layers of the colon. Intestinal extracellular matrix (ECM) remodeling is highly dynamic during disease activity and blood spillover of ECM components might reflect transmural disease burden. The aim of this study was to evaluate baseline serum markers of ECM formation (PRO-C11, PRO-C22, and PRO-C7) and degradation (C7M) to assess disease activity and treatment response in UC. Methods Forty-nine UC patients with active disease and 50 healthy controls (HC) were included. All underwent endoscopy and blood sampling at inclusion. UC patients additionally had fecal calprotectin (FCP) measured at baseline and had treatment adjusted at the discretion of the attending physician. Subsequent follow up of UC patients included clinical activity score, FCP, and blood samples at 3 and 6 months as well as an endoscopy at 6 months. Ulcerative Colitis Endoscopic Index of Severity (UCEIS), total Mayo score (TMS), and disease extent (E1-E3) was registered. Response was defined as a reduction from severe to moderate or mild disease based on TMS. If no follow-up endoscopy was performed (n=9), partial Mayo was used. Spearman’s correlation and one-way-ANOVA with Turkey correlation and correction for multiple testing were applied for statistical analysis. Results All markers of ECM degradation and formation were elevated in patients with severely active UC measured by both UCEIS and TMS compared to HC (adjusted p<0.0001 for each marker). CM7 and PRO-C22 differentiated moderate from severe UC by TMS (p<0.0001) and UCEIS (p<0.05) (Figure 1A-B). Baseline C7M, PRO-C7, and PRO-C11 correlated with CRP (Spearman’s: r=0.82, p<0.0001; r=-0.45, p=0.0012; and r=-0.33, p=0.032, respectively). None of the markers correlated with FCP. Elevated C7M, PRO-C7, and PRO-C11 levels for E3 could differentiate E3 from E1 (Difference ng/ml: 3.89 (SE of diff: 1.47), 13.15 (4.55), 10.08 (4.09), respectively, all p<0.05) (Figure 1C-E). Remission was achieved in 18/49 patients at 6 months. Both C7M and PRO-22 exhibited acceptable discriminative capabilities at baseline for 6-month TMS between remission and non-remission (AUC 0.72 (95% CI 0.58-0.87) p=0.01 and AUC 0.68 (95% CI 0.53-0.83) p=0.04, respectively) (Figure 1F-G). Conclusion This study demonstrates that ECM markers correlate with disease activity, disease extent, and predict future disease outcome in UC. ECM markers hold great promise as they provide a 'window' into transmural tissue remodeling and inflammatory and fibrotic burden, warranting further investigation.

P131 Therapeutic effects of KPG-818 in a trinitrobenzene sulfonic acid - induced mouse Crohn's/Ulcerative Colitis model

Abstract Background Immunomodulatory drugs have the potential therapeutic benefit not only in malignancy but also in diseases characterized by an inflammatory phenotype. In inflammatory bowel diseases (IBD), colonic inflammation results from dysregulation of the mucosal immune responses to intestinal flora together with genetic and environmental factors. Inflammatory cytokines are implicated in pathogenesis of IBD. Treatments for IBD that improve clinical outcomes and limit adverse effects are needed. KPG-818 is a novel generation of lenalidomide derivative and small molecule immunomodulatory drug. KPG-818 is currently under clinical development for therapy of multiple myeloma, lymphoma (phase 1), and systemic lupus erythematosus (SLE) (phase 2a). Remarkable immunomodulatory effects of KPG-818 are observed in SLE patients. In preclinical studies, KPG-818 significantly inhibits inflammatory cytokines interleukin-6 and TNF-α in human peripheral blood mononuclear cells, inhibits tumor growth in multiple myeloma and lymphoma xenograft tumor models. Here we report the significant therapeutic effects of KPG-818 in a chronic Crohn’s/ulcerative colitis mouse model. Methods Trinitrobenzene Sulfonic Acid (TNBS) was intra-colonially administered to induce Balb/c mouse Crohn’s/ulcerative colitis model at 50 mg/kg, once a week for 4 weeks. KPG-818 was orally administered at doses of 0.03, 0.12, 0.4, and 1.0 mg/kg, once a day for 6 consecutive weeks. Upadacitinib served as a positive control drug. Vehicle solution served as a negative control. To evaluate the therapeutic effects of the KPG-818, disease activity index (DAI) of ulcerative colitis, the degree of weight loss, fecal morphology, and rectal bleeding were scored once every other day for six consecutive weeks. At the end of the study, colonic samples were collected for gross observation and scoring of macroscopic damage, measurement of length and weight, and histopathological diagnosis and scoring. At the end of study, peripheral blood samples were also collected for analyses of immune cells and cytokines. Results Compared to the vehicle control, KPG-818 significantly improved the body weight loss, disease activity of ulcerative colitis, gross degree of colorectal injury, pathological lesions of colorectal tissue, inhibited the inflammatory cytokines in a dose-response manner. The effective dose was as low as 0.03 mg/kg. KPG-818 showed similar therapeutic effects to Upadacitinib. Conclusion In this mouse model of chronic Crohn’s/ulcerative colitis, KPG-818 showed remarkable therapeutic effects in a dose-dependent manner. These data encourage the clinical evaluation of KPG-818 in inflammatory bowel diseases.

P280 Comparative responsiveness of disease activity indices in moderately-to-severely active Ulcerative Colitis: a post-hoc analysis of the UNIFI trial

Abstract Background Clinical, endoscopic, histological, and composite instruments are used to measure disease activity in ulcerative colitis (UC). We compared responsiveness of the Mayo Clinic Score (MCS), modified Mayo Clinic Score (mMS), partial Mayo Clinic Score (pMS), Robarts Histopathology Index (RHI), and UC-100 score after treatment with ustekinumab in patients with moderately-to-severely active UC. Methods Publicly available data from the phase 3 UNIFI induction trial (NCT02407236) comparing the efficacy and safety of ustekinumab versus placebo in patients with moderate-to-severe UC were obtained from Vivli (Vivli ID #7549) and Yale University Open Data Access Project (#2021-4848). Post-hoc analyses were performed on patient level data to ascertain outcomes of interest. Treatment assignment was the criterion for change in evaluation of responsiveness, which was quantified using the probability of a treated patient having a larger change than a placebo patient (win probability [WinP]) and estimated using nonparametric methods. Extent of responsiveness was interpreted according to Cohen’s benchmarks as very small (WinP<0.56); small (0.56≤ WinP<0.64); medium (0.64≤ WinP<0.71); and large (WinP≥0.71). Results Data from 961 patients with moderately-to-severely active UC randomised in UNIFI were included. At baseline, 319 patients received placebo and 624 patients received ustekinumab. A total of 912 (94.9%) patients completed the induction trial. Overall mean baseline index scores were: MCS 8.9 (±1.6), mMS 6.6 (±1.3), pMS 6.2 (±1.4), RHI 16.6 (±8.1), and UC-100 score 71.4 (±16.5) (Table). The UC-100 demonstrated a large degree of responsiveness (WinP 0.72 [95% CI: 0.66, 0.78]). The MCS (0.68 [0.62, 0.73]), mMS (0.69 [0.63, 0.75]), and pMS (0.65 [0.59, 0.71]) demonstrated similar, medium effect sizes (all comparisons p>0.05) (Figure). The RHI alone had a relatively small effect size (WinP 0.63 [0.56-0.70]). Among individual UC-100 components (Mayo Clinic stool frequency subscore, Mayo Clinic endoscopic subscore, and RHI), the endoscopic score was most responsive (WinP 0.59 [0.36-0.82]). The combination of endoscopy and RHI was associated with a medium degree of responsiveness (WinP 0.69 ([0.34, 1.00]). Conclusion UC disease activity indices are similarly responsive to change. Depending on trial design and measurement feasibility, different instruments can be considered optimal for evaluation of efficacy. The mMS is similarly responsive to the MCS without including the physician global assessment and may be more appropriate for determining trial eligibility and defining primary endpoint, whereas the UC-100 may be more appropriate for measuring treatment effect when an objective continuous measure is needed.

P031 Microbiota-driven appendiceal B lymphocytes aggravate DSS-induced murine colitis through facilitating colonic CD4+ T cells polarization

Abstract Background The appendix is an immunological organ sustaining a microbiome inoculum that plays a vital role in intestinal mucosal immunity and colonic microbiome stability. Previous studies have proposed the appendix exerts effects on ulcerative colitis (UC)’s pathogenesis, but the nature and basis underlying this connection remain unclear. B lymphocytes account for the largest proportion of appendiceal immunocytes and activate in the experimental colitis model, we systematically investigated how appendiceal B lymphocytes (appB) participate in UC’s pathogenesis and provided rational evidence for appendectomy and B cell immunotherapy being used in UC treatments. Methods The chronic colitis model was established in C57BL/6J mice by three cycles of 2% dextran sodium sulfate (DSS) treatment. Bulk RNA sequencing and 16S rRNA sequencing were used to explore appB’s characteristics and the potential causes of appB activation in DSS-induced colitis. Adoptive appB transfer and intravital imaging were used to evaluate appB’s homing and functional features in DSS-induced chronic colitis. Magnetic microbead-based cell sorting and cells experiments in vitro were used to investigate the underlying mechanisms of appB’s activation and effects on DSS-induced chronic colitis. Flow cytometry was used to assess the colonic mucosal adaptive immunity alterations in colitis mice adopted appB. Results Firmicutes and Bacteroidetes are the dominant phylum in the normal appendix, while Firmicutes, Verrucomicrobia, and Proteobacteria are prominent in the colitis appendix. The appendiceal IgG+ B cells expended in colitis mice compared with the normal mice; and the DSS colitis appB (DSS_appB), compared with the normal control appB (NC_appB), had much more potential to migrate to the colon and fired the gut flare, accompanied by the increment of CD19+ IgG+ cells, CD4+ IFN-γ+ cells and CD4+ IL-17+ cells in the colonic lamina propria in colitis mice. In vitro, DSS_appB secreted more inflammatory cytokines (IFN-γ, IL-6) than NC_appB under the stimulation of Toll-like receptor agonist analogs (Pam3CSK4, LPS, and ODN1826); DSS_appB facilitated colonic CD4+ T cells to secrete IFN-γ and IL-17 by up-regulating surface marker (CD80/86) and secreting IFN-γ and IL-6. Conclusion In DSS-induced chronic colitis mice, appB activated, driven by appendiceal microbiota,migrated to the colonic lamina propria and aggravated colitis through facilitating CD4+ Tcells polarize to Th1 and Th17 by up-regulating CD80/86 and secreting IFN-γ and IL-6 (Figure 1). Our research provides evidence for the connection between the appendix and UC, and we propose that appendectomy or B cell immunotherapy is promising to treat UC.

P1041 Coconut water modulates dietary potassium and gut microbiome to induce remission in ulcerative colitis: randomized controlled trial

Abstract Background High potassium intake is associated with decreased risk of inflammatory bowel disease(IBD), urinary potassium has been correlated with disease activity in ulcerative colitis(UC), and gut microbiome modulation improves outcomes in UC. We evaluated coconut water as potassium rich diet and gut microbiome modulator in patients with mild-moderate UC. Methods This single-center double-blind placebo-controlled trial randomized patients with mild-moderate (simple clinical colitis activity index-SCCAI:3–9) endoscopically active UC (ulcerative colitis endoscopic index of severity-UCEIS>1) in 1:1 ratio to coconut water + standard medical therapy-SMT(CW) vs placebo + SMT. 400ml of coconut water (200-250mg potassium/100ml) was administered for 8 weeks. Primary outcome measure was clinical remission (SCCAI ≤ 2) and secondary outcome measures were clinical response (SCCAI decline ≥ 3) and adverse events at 8 weeks. Microbiome was analyzed at baseline and 8 weeks. Results Of 121 patients screened, 95 were included for modified intention to treat analysis(49-CW, 46-placebo)[mean age-37.2 ± 11.2years; males-54.1%; disease duration-48 (IQR:24–90) months; pancolitis - 26.1%; SCCAI-5 (IQR:4 – 6); UCEIS-4 (IQR:3 – 5)]. There was significant increase in dietary potassium and decline in sodium/potassium ratio at 8 weeks in CW. Clinical response [57.1% vs 28.3%, p=0.01, OR-3.4 (95%CI:1.4 – 7.9)], remission [53.1% vs 28.3%, p=0.02, OR-2.9(95%CI:1.2 – 6.7)] and proportion of patients with fecal calprotectin (FCP)<150μg/g [53.6% vs 14.3%, p=0.01, OR-6.9(95%CI:1.6 – 28.9)] were significantly higher in CW. The relative abundance of bacterial taxa which had a significant or trend towards negative correlation with SCCAI, UCEIS, or FCP, increased at 8 weeks in CW. Adverse events were comparable and no patient developed hyperkalemia. Conclusion Coconut water increased dietary potassium, modulated the gut microbiome and was more effective than placebo for induction of remission in mild-moderate UC.

P235 Correlation of mental and psychological status to disease activity in patients with Inflammatory Bowel Disease using The Symptom Checklist -90- Revised Questionnaire (SCL90R)

Abstract Background Inflammatory Bowel Disease can affect mental health. There is no evidence that stress is a direct cause of the disease. Most Inflammatory Bowel Disease patients describe an emotional impact, mainly feelings of depression and anxiety. Many questionnaires used to assess anxiety in those patients including Symptom Checklist -90-Revised Questionnaire. This research aimed to investigate Correlation of mental and psychological status to disease activity in patients with Inflammatory Bowel Disease using Symptom Checklist -90-Revised Questionnaire. Methods The study included one hundred patients (50 Crohn's Disease patients – 50 Ulcerative Colitis patients). Detailed history taking, systemic physical examination, laboratory investigations, Colonoscopy, Symptom Checklist -90-Revised Questionnaire. A self-report psychometric instrument (questionnaire) for every patient. Results The mean age of Crohn’s Disease patients was 24,2 years +/- SD 3,6 years. In Ulcerative Colitis patients the mean age was 28,5 years +/- SD 7,3 years. No age or gender relation could be detected with Symptom Checklist -90-Revised Questionnaire score in both groups, The study showed a direct correlation of Crohn's Disease Activity Index (CDAI) and endoscopic activity (Simple Endoscopic Score) (SES) to Symptom Checklist -90-Revised Questionnaire. There was direct correlation of Ulcerative Colitis disease activity (Simple Clinical Colitis Activity Index) (SCCAI) and Endoscopic activity (Ulcerative Colitis Endoscopic Index of Severity) (UCEIS) to Symptom Checklist -90-Revised Questionnaire. Conclusion There is a direct correlation of disease activity and Endoscopic activity in Ulcerative Colitis and Crohn's Diseases to Symptom Checklist -90-Revised Questionnaire.

P412 Faecal Calprotectin as a predictor of endoscopic and histologic remission in patients with Ulcerative Colitis

Abstract Background Faecal calprotectin (FCP) is a reliable surrogate marker for disease activity in ulcerative colitis (UC). However, there are no consensus cut-off values for histoendoscopic remission. The aim of the study is to correlate FCP with Mayo Endoscopic Score (MES) and histological disease activity (Geboes score) of UC patients in clinical remission. Methods We performed a prospective study including adult UC patients at the McGill IBD Center between 2013 and 2017. Patients in clinical remission (partial Mayo score ≤2) or disease relapse, undergoing endoscopy for disease activity or dysplasia surveillance, were enrolled. Before bowel preparation, FCP was collected. MES was documented during colonoscopy. Biopsies were taken throughout the colon and histological activity was assessed using Geboes score (GS) by a blinded expert gastrointestinal pathologist. Results The study included 253 patients, of which 117 (46%) were male with a mean age of 38.2 years (standard deviation [SD] ± 24.8). 46% of the patients had pancolitis at the time of colonoscopy. 5-aminosalicylate were used by 68.4% of patients while 20.9% were on immunomodulators, 19% on biologics and 0.4% on small molecules as treatment. Regarding endoscopic correlation, it showed that an FCP ≥ 200 μg/g predicts MES > 1 despite clinical remission, yielding sensitivity of 59% and specificity of 74%. A FCP ≥ 123 predicts MES > 0 despite clinical remission (58% sensitivity and 70% specificity), also aiding to differentiate MES 0 from MES 1 (61% sensitivity and 70% specificity). As to histologic correlation, a FCP ≥ 80 μg/g identified histological disease activity using Geboes criteria (GS score > 3.1) in patients with clinical remission, yielding 64.7% sensitivity, 58.7% specificity and 77% positive predictive value (Figure 1). When using a GS score threshold of > 2, a cut-off value of FCP ≥ 50 μg/g, appears to be the most clinically relevant to identify patients in clinical remission who continue to have active histologic inflammation, with an 49.6% sensitivity, 41.6% specificity and 40% positive predict value. Results are summarized in Table 1. Conclusion FCP correlates very well with endoscopic and histologic disease activity and can be used as a surrogate marker for disease activity. Our study prospectively demonstrated the optimal cut-off values helping to discriminate endoscopic healing and histologic remission.

P357 Automated assessment of histological disease activity in Ulcerative Colitis using a deep learning algorithm

Abstract Background Assessment of histological disease activity in patients with ulcerative colitis (UC) is becoming more important. Therefore, the DCA score was developed for use in clinical practice. Distribution (D), chronicity (C) and activity (A) are each scored on a three-point scale with distribution being dependent on the percentage of biopsy area affected by inflammatory changes. A major problem for implementation of any score is interobserver heterogeneity. To overcome this hurdle, we developed a deep learning algorithm to automatically compute the DCA score. Methods A retrospective cohort was created consisting of 117 adult patients with ulcerative colitis from which biopsies were taken during a colonoscopy performed in the setting of routine clinical evaluation (training set of 537 slides). From 75 cohort patients, an additional set of biopsies was available (test set of 299 slides). An expert gastrointestinal pathologist performed the DCA score. The model was trained on H&E-stained whole slide images scanned at 40x (0.243-μm pixel) resolution. Training was performed in a weakly supervised multiple-instance learning setup, using slide-level labels without region of interest annotations. The features from the convolutional neural network-based model trained at 2.5x, 5x, and 10x magnification were incorporated using a random forest classifier for final prediction. Model accuracy was evaluated using the test set. Results The algorithm differentiates between normal and inflamed with an accuracy of 90.9% (Table 1). Model performance from features aggregated across all magnification levels (i.e., 2.5x, 5x, and 10x) was superior to features from individual levels. This can be explained with the help of GradCam heatmaps (Figure 1), where we show that features learned at different magnification levels correspond to different aspects of histological changes in UC. The multiple instance approach did not appear to detect crypt abscesses, which may have resulted in a relatively poor performance in differentiating A1 from A2. The model accuracy for the 9-class DCA was 64.8%. Conclusion The algorithm first appears to assess architectural distortions at lower magnification and then the presence of cellular elements like neutrophils at higher magnification. This closely mirrors the approach of pathologists. The present model automates the scoring process and by supporting the daily diagnostic practice highlights the potential of deep learning technologies in assessment of histological disease activity in UC.