Mayo Endoscopic Score Research Articles

USEFULLNESS OF SERUM LEUCINE-RICH ALPHA2-GLYCOPROTEIN AND FECAL CALPROTECTIN ASSURROGATE MARKERS IN ULCERATIVE COLITIS

Abstract BACKGROUND AND AIM Serum Leucine-rich alpha-2 glycoprotein (LRG) was identified as a novel biomarker for rheumatoid arthritis and IBD by using a proteomics approach. Several studies have suggested that serum LRG levels and fecal calprotectin (fCal) were correlated with clinical activities in patients with ulcerative colitis (UC). We compared utility of these biomarkers for monitoring disease activity in UC. METHODS A single-center observational study was conducted at Kyushu University Hospital. A total of 101 patients who underwent colonoscopy during the period from February to December 2021 were enrolled. The associations between endoscopic and histological activity and biomarkers were investigated. Endoscopic activity was defined as Mayo endoscopic score (MES) of 1 or less for mucosal healing and 0 for complete mucosal healing. For histological activity (n=90), Geboes score of 2 or less was defined as histological remission. RESULTS Subjects ranged in age from 16 to 80 years (35 males and 66 females). There were 63 cases of total colitistype, 32 cases of left-sided colitis type, and 6 cases of proctitis type. The MES at enrollment were as follows: MES 0 in 41 cases, MES 1 in 33 cases, MES 2 in 19 cases, and MES 3 in 8 cases. In comparison between the mucosal healing and non-mucosal healing groups, LRG was significantly lower in the mucosal healing group (p<0.0001). The correlation coefficient of LRG with MES was r=0.614 (p<0.0001), which was higher than that of fCal, r=0.414 (p<0.0001). In ROC analysis with mucosal healing as the outcome, the AUC and cut-off value of LRG were 0.781 and 17.9 μg/ml, respectively, and for fCal were 0.850 and 396 μg/g, respectively. In the ROC analysis with complete mucosal healing as the outcome, the AUC for LRG was 0.690, which was lower than the AUC of 0.846 for fCal . When compared by histological remission, LRG was lower in the histological remission group (p<0.001). In the ROC analysis with histological remission as the outcome, the AUC for LRG was 0.722 (cutoff value 14.2 μg/ml) and for fCal was 0.837 (cutoff value 119 μg/g). CONCLUSION Both LRG and fCal are valuable biomarkers reflecting disease activity in UC.

LIQUID-BIOPSY FOR ASSESSING SEVERITY OF INFLAMMATORY BOWEL DISEASE VIA PLASMA MICROBIAL CELL-FREE DNA

Abstract Plasma cell-free DNA (cfDNA) has emerged as a robust biomarker utilized in multiple applications that span cancer screening, diagnosis and monitoring, prenatal testing, and characterization of organ health post-transplantation. Cell-free DNA-based assays leverage the occurrence of processed extracellular DNA that produce unique signatures to discern a variety of biological states, disease manifestations, as well as forms of cell death. Similar to human cells, microbes produce cfDNA when they turnover, providing evident clinical utility in diagnosing and treating deep-seated infections in immunocompromised patients. Here, we describe the use of plasma microbial cell-free DNA (mcfDNA) as a unique means to assess inflammatory bowel disease type and severity. A total of 392 plasma samples encompassing remission and active (mild, moderate, severe) Crohn’s disease (N=196) and ulcerative colitis (N=196) were provided by the Crohn’s and Colitis Foundation for this study. All samples were derived from patients who had an endoscopic assessment within a 30-day window of plasma collection. Our classifiers, based solely on plasma mcfDNA signatures, are able to discriminate between Crohn’s disease, Ulcerative colitis, or otherwise healthy patient populations with an AUC >0.95. Similarly, a second set of classifiers are able to distinguish between endoscopically validated remission, mild, moderate, and severe disease cases (as determined by Mayo Endoscopic score or Crohn’s disease activity index) with AUCs >0.75. These results correspond to greater than 37% (UC) and 18% (CD) increase in sensitivity in comparison to standard of care measurements via fecal-calprotectin and high sensitivity-C-reactive protein for this cohort. Upon investigation, critical features in our classifiers correspond with well-known signatures from microbes associated with IBD or well-curated from the human microbiome. The use of mcfDNA for IBD diagnosis and assessment of disease severity may provide clinicians and patients a valuable non-invasive means to gain additional insight into disease progression in a routine manner. Further opportunities to leverage these signatures to predict response to therapy, and validate classifier performance on an independent cohort are currently being explored.

FECAL URGENCY ASSOCIATED WITH POOR QUALITY OF LIFE IN QUIESCENT IBD: A CROSS-SECTIONAL STUDY OF SPARC IBD COHORT

Abstract BACKGROUND Fecal urgency (FU) is common in patients with active inflammatory bowel disease (IBD) and has been associated with reduced well-being and poor quality of life (QOL). Despite greater therapeutic options, clinical symptoms may persist in some patients. Data is lacking regarding FU in patients with objectively documented quiescent disease. OBJECTIVE Among endoscopic quiescent disease: (1) estimate prevalence of urgency, (2) assess predictors of FU, (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 urgency was categorized as none, mild, or moderate/severe. Univariate statistics used Pearson’s Chi-square and Kruskal-Wallis tests. RESULTS A total of 943 patients with quiescent IBD (579 CD; 364 UC) were included in the study (Table 1). Fecal urgency was more commonly reported in quiescent CD (37.5% mild, 27.8% moderate/severe) as compared to quiescent UC (33.5% mild, 19.8% moderate/severe) (p<0.001). In the entire quiescent cohort, those with mild or moderate/severe FU were more likely to be female sex (58.4%; 63.2%), higher BMI (28.2; 29.5) and have an IBD-related surgery (p=0.030). Mild and moderate/severe urgency was associated with subjective abdominal pain, stool frequency, and bloody stool (all p<0.001). There was a trend towards ileocolonic involvement and penetrating disease in quiescent CD with moderate/severe urgency. General well-being was poorer for those with more severe urgency (p<0.001), and they were more likely to utilize the emergency department (p=0.016). Figure 1 depicts the PROMIS responses. There were significant differences across all domains, and notably those with moderate/severe urgency reported pain (38.8%) and fatigue (60.0%) interfered with enjoyment of life at least some of the time compared to those without urgency (3.9%; 10.0%) or with mild urgency (15.1%; 32,2%). CONCLUSION In this study of patients in SPARC IBD with endoscopic quiescent IBD the overall prevalence of fecal urgency was 65.2% for CD and 53.3% for UC. Fecal urgency was common in quiescent IBD and associated with poorer general well-being and quality of life. Further research is needed to elucidate the pathophysiology for presence of fecal urgency in quiescent IBD and develop personalized management approaches. Table 1 Demographics and IBD characteristics of SPARC IBD patients with quiescent Crohn’s disease (CD) and ulcerative colitis (UC) with symptoms of mild versus moderate/severe fecal urgency. Table 2 Severity of Fecal Urgency on Quality of Life for Patients with Endoscopic Quiescent IBD using PROMIS (Patient-Reported Outcomes Measurement Information System) Scores for Fatigue, Pain Interference† and Social Interference†*. †Responses indicate the degree and frequency of interference with each of the activities listed. *Polarity of Social Interference subscale reversed for consistency and interpretability of the figure.

P356 Long-term outcome of UC patients in clinical remission with different level of mucosal activity: real world, retrospective, multicontinental study

Abstract Background In contrast to the increasingly rigorous endpoints of clinical trials of ulcerative colitis (UC), Mayo endoscopic score (MES) ≤ 1 is mostly set as target during clinical follow-up, but long-term outcomes may differ according to different level of healing. Therefore, our study aimed to compare the long-term outcomes of UC patients in clinical remission with different MES and UCEIS scores in real-life condition. Methods UC patients in clinical remission (defined by pMayo<2 with no rectal bleeding) who underwent colonoscopy between 2016-2020 were consecutively enrolled in this multicenter retrospective study. Mayo and UCEIS endoscopic scores were evaluated and clinical and demographic data were collected at baseline. Clinical flare, colectomy, hospitalization and treatment modifications were recorded during at least 3 year of follow-up. Primary outcome was the clinical flare, while secondary outcomes were hospitalization, colectomy, new biological initiation and biological dose escalation during follow-up. Outcomes were compared with Log-rank test and survival characteristics were plotted. Results In total, 156 UC patients were enrolled with a median age of 46.0 (IQR 35.5-58.0), while male/female ratio was 49.4 % (Table 1.). Near to half of the patients (44.9%) had MES>0 endoscopic activity at baseline. Non zero baseline MES (Figure 1.; p = 0.002; MES 0 vs 1 p = 0.004) and UCEIS (p < 0.001; UCEIS 0 vs. 1 p = 0.016) scores were associated with higher rate of clinical flare. Higher baseline MES (p = 0.042) and UCEIS (p = 0.008) scores were coupled with increased risk of hospitalization. Colectomy rates were low. Increased baseline UCEIS (p = 0.003), but not MES score was coupled with new biological treatment initiation, while only UCEIS score was associated with biological treatment intensification (>4; p = 0.008). Conclusion Our study suggests differentiating between complete MH from MES 1 as long-term outcomes were more favorable in case of lower endoscopic scores. Consequently, targeting complete MH should be considered to achieve deep remission and disease clearance.

P021 Higher TNFα and IL-6 mucosal levels in ulcerative colitis patients with more severe endoscopic activity

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterised by colonic mucosa inflammation. Its clinical course is marked by alternating periods of relapse and remission that impair patients' quality of life. In the last decades, novel therapies have shown to be effective for UC resulting in lower rates of colectomy. However, there is still a significant proportion of non-responding patients that change from one treatment to another, being exposed to its potential adverse events. Thus, predictive factors of response to available drugs are needed to tailor the best treatment strategy for each patient. The aim of our study was to measure TNFα and IL-6 levels in colonic biopsies from patients with UC with moderate to severe endoscopic activity. Methods A prospective, observational single-centre study was designed and it is currently on going. Adult UC patients with moderate to severe endoscopic activity (Mayo Endoscopic Score (MES) > 1) in a routine colonoscopy were included. Biopsies from inflamed (MES>1) and non-inflamed (MES=0) colon of each patient were homogenised and processed by using RIPA buffer and ultrasounds to obtain cell lysates. Human Luminex Discovery Assay (2 plex) was used for the simultaneous detection and quantitation of IL-6 and TNFα. Data are shown as percentage, median, interquartile range (IQR) and mean ± standard deviation (SD) as appropriate. Results So far, 21 patients were consecutively included (mean age 53.8 years (SD 17.0), 52.4% female). About 43% of patients had left-sided UC, 28.5% extensive UC and 28.5% proctitis. Regarding endoscopic activity, 61.9% of patients showed MES=2 and 38.1% were MES=3. Fourteen patients (66.6%) were bio-naïve and 7 (33.3%) had been exposed to anti-TNFα. IL-6 was detected in biopsies from colon with MES ≥ 2 of 18 (85.7%) patients, of which 10 (55.6%) patients also TNFα was found. Neither IL-6 nor TNFα were detected in biopsies from non-inflamed colon (p=0.00). Median IL-6 in inflamed colonic samples from patients with MES-2 was 25.6pg/ml (IQR 0.2-74.3) and 92.2pg/ml (IQR 16.9-314.3) in those with MES-3 (p=0.09). Median TNFα in inflamed colonic biopsies from patients with MES-2 was 0.0pg/ml (IQR 0.0-20.0) and 22.2pg/ml (IQR 0.0-34.3) in patients with MES-3 (p=0.12) (Figure 1). No differences were found in TNFα levels between anti-TNFα naïve patients and those patients previously exposed to anti-TNFα (p=0.96). Conclusion IL-6 and TNFα are elevated in inflamed colonic mucosa, particularly in those patients with more severe endoscopic activity, while they are not found in non-inflamed colonic mucosa. The correlation between cytokine levels and endoscopic severity suggests their potential as biomarkers for treatment response.

P267 Prospective validation of the IBD - Distribution, Chronicity, Activity (DCA) histological score for Ulcerative Colitis and correlation with UCEIS and MES

Abstract Background Histological assessment is not currently recognised as an independent parameter to guide personalised treatment for patients with ulcerative colitis (UC). The development of the Inflammatory Bowel Disease – Distribution, Chronicity, Activity (IBD-DCA) score allows a pragmatic approach to quantitatively evaluate mucosal injury and healing in UC, compared with other pre-existing histological scores (Lang-Schwarz et al., J Crohns Colitis, 2021). This scoring system facilitates a template-based reporting to produce consistent reports with information representing UC severity. Each domain of the IBD-DCA is scored as one of 0 (normal), 1 (mild), or 2 (moderate to severe) based on the presence of established histological UC findings (Figure 1). This project aims to prospectively validate the IBD-DCA score for routine clinical deployment and correlate with endoscopic scores – UC Endoscopic Index of Severity (UCEIS) and Mayo Endoscopic Score (MES). Methods Colonoscopic biopsies from patients with a previously confirmed diagnosis of UC attending one of four hospitals in a single healthcare group from August 2022 to January 2023 were reported using the IBD-DCA histological score, and the corresponding, clinician-reported UCEIS and MES scores were recorded. The histopathology reports were assessed based on the completeness of information in their respective D, C, and A domains. The proportion of reports with information fully represented by the IBD-DCA reporting template and the distribution of biopsy sites were described. The correlation between IBD-DCA with UCEIS and MES was quantified via Kendall’s tau (τ) using the R statistical package v4.3.2. Results Of the 151 cases reported, 70 (46.4%) patients were female and 81 (53.6%) were male. 12 patients (7.9%) had full colonic biopsies, while the remaining cases were assessed with selective biopsies. Rectal biopsy was most often performed (83.4%). The IBD-DCA components were reported for every biopsied sites in 133 (88.1%) cases. Notable correlations included UCEIS vascular pattern with histological chronicity (τ = 0.3891), UCEIS erosions/ulceration with histological activity (τ = 0.3252), and histological activity with the total UCEIS score (τ = 0.3450). MES showed the strongest correlation with histological disease distribution (τ = 0.3450)(Table 1). All p-values < 0.001. Conclusion These data show encouraging uptake of this simple histological reporting template in UC in daily routine use. The findings suggest that the IBD-DCA score may be a useful addition in the clinical management in patients with UC.

P691 Intestinal ultrasonography accuracy in the evaluation of patients with moderate to severe ulcerative colitis starting infliximab therapy

Abstract Background The diagnostic accuracy of detecting active ulcerative colitis (UC) by transabdominal intestinal ultrasonography (IUS) is well described. However, the value of repeated IUS measurements in tight monitoring during treatment remains to be established. The aim of the study is to evaluate the utility of IUS for monitoring biologic therapy in UC. Additionally, to establish the correlations between IUS findings and the endoscopic Mayo score (EMS), as well as clinical and biochemical severity indices. Methods In a prospective open-label study, individuals with moderate to severe ulcerative colitis who were initiating infliximab therapy were included, excluding those with proctitis. Patients were evaluated at baseline and after 3 months of biologics induction by means of clinical, biochemical, endoscopic mayo score, and IUS assessments. A Paired Wilcoxon analysis was conducted to compare data before and after therapy induction. The correlation between bowel wall thickness (BWT) and the endoscopic mayo score (EMS), C-reactive protein (CRP), calprotectin, and the Simple Clinical Colitis Activity Index (SCCAI) was analyzed across both visits. Results Thirty-two patients were enrolled and completed baseline evaluations and 21 completed follow-up assessments. The median age was 38 years (IQR 29-60), with 53% male, a median disease duration of 7 years (6-9), 41% having left-sided colitis, and 59% with pancolitis. All patients were treated with infliximab. No significant differences were observed at both time points in terms of BWT, EMS, CRP, and calprotectin (5.5 vs 4.4, p=0.2; 2 (2-3) vs 2 (1-3), p=0.4; 9.4 vs 9.6, p=0.4; 979 vs 394, p= 0.1, respectively). The only significant improvement was in terms of SCCAI (7 (4.8-8) vs 3 (1-5), p=0.009). BWT showed significant correlations with EMS (r= 0.43, p= 0.0015) (figure 1), CRP (r= 0.40, p= 0.007), and SCCAI (r= 0.28, p= 0.03), while no correlation was found with calprotectin (r= 0.19, p= 0.25). Conclusion Intestinal ultrasonography could serve as a substitute for lower endoscopy in evaluating disease activity.

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.

P386 Persistence of bowel urgency despite clinical remission after induction therapy is associated with unfavorable long-term outcomes in patients with ulcerative colitis: results from the multicenter UC-RGENCY study

Abstract Background STRIDE 2 recommendations define clinical remission as no rectal bleeding and normalization of stool frequency in patients with ulcerative colitis (UC), without including bowel urgency (BU) despite its negative impact on quality of life. In this large multicenter cohort, we aimed to assess whether the persistence of BU after induction therapy is independently associated with poor long-term outcomes in patients with UC. Methods From a multicenter retrospective study, we included consecutive UC adult patients previously exposed to at least one anti-TNF agent, with partial Mayo score (pMS) > 2, who started biologics or small molecules between Jan2019 and June2022. BU was defined as a binary criterion based on the SCCAI definition. The primary endpoint was the time to drug discontinuation due to active UC. Secondary endpoints were time to relapse, time to colectomy as well as steroid-free clinical remission (pMS ≤ 2) (CFREM), endoscopic remission (CFREM + Mayo endoscopic score (MES) ≤ 1), and mucosal healing (CFREM + MES ≤ 1 + histological remission i.e. Nancy index ≤ 1) at last follow-up. Results Among 473 patients with UC, 270 were assessed for BU after induction therapy (week 16) (mean age 43.0±17.0 years-old, median UC duration 6 [3-11] years, female gender=54.0%, pancolitis=45.9%). The median follow-up was 14 [8-22] months. The rate of CFREM after induction therapy was 54.4% (147/270) while 21.5% (58/270) had remaining bowel urgencies after induction therapy. Among the 147 patients achieving remission after induction therapy, 12 had persistent BU (8.2%), while 62.6% (77/123) of patients with no CFREM after induction therapy did not have any BU. The agreements between BU and rectal bleeding (75.2%, κ-coefficient = 0.33±0.06) or normalization of stools frequency (67.9%,κ-coefficient = 0.35±0.05) were mild. Among the patients with persistent BU after induction therapy, only 3.7% had no endoscopic activity (MES = 0). In multivariable analyses including CFREM at week 16, persistence of BU after induction therapy was independently associated with the time to drug discontinuation (HR=2.0[1.1-3.5], p=0.016) and colectomy (HR=4.4[2.3-8.4], p<0.001), and absence of mucosal healing (OR = 5.0[1.1-24.8], p=0.046) at last follow-up. A trend was also observed regarding the association between remaining BU after induction therapy and no CFREM (OR=6.1[0.8-48.0], p=0.085) or absence of endoscopic remission (OR=2.4[0.9-6.1], p=0.077) at last follow-up. Conclusion Persistence of BU despite clinical remission is associated with higher risk of drug discontinuation due to active UC, colectomy and lower likelihood of mucosal healing. Bowel urgency should be implemented into international guidelines to define clinical remission in patients with UC.

P965 Ulcerative proctitis treated with biologics: is it too hard to treat?

Abstract Background Patients with ulcerative proctitis are widely considered a challenging population because the reported reduced response rate to conventional medical treatment. On the other hand, data on the role of biological therapies in this specific cohort are currently scarce Methods We retrospectively evaluated all patients with proctitis (defined as the mucosal inflammation of only the rectum with ulcerative colitis confirmed by histology) treated with biologics (infliximab, adalimumab, vedolizumab -VDZ-, ustekinumab -UST) and tofacitinib (TOFA) at four referral centers in the last 5 years. All patients were treated with concomitant topical mesalamine. We included in this study only patients who underwent colonoscopy at baseline and after 52 weeks of treatment, in order to evaluate therapeutic response in terms of mucosal healing (defined as a Mayo Endoscopic Score -MES- <2), besides that clinical remission (defined as a Partial Mayo Score -PMS- <2 without oral or topical corticosteroid therapy). We collect clinical and demographic data, as well as fecal calprotectin (FC) and C-Reactive Protein (CRP) levels at baseline and after the induction of therapy Results Among 64 patients enrolled (age 50.8±16.5 years, 29 [45.3%] women), 33 (51.6%) were treated with anti-TNF), 15 with VDZ, 13 with UST, and 3 with TOFA. Globally, 51 (79.7%) patients achieved clinical remission and 37 (57.8%) patients achieved endoscopic remission at 52 weeks. There were no group differences in age, sex, BMI, disease duration, PMS, MES, drug, or baseline CRP levels between patients achieving or not either clinical or endoscopic remission. Baseline calprotectin levels were lower in patients who achieved endoscopic remission (median [IQ range] 297 [158, 475] versus 442 [230, 1545] µg/mL, p=0.036), but not in those who achieved clinical remission. After the induction phase, lower calprotectin levels were observed in patients achieving clinical (46 [15, 166] versus 553 [72, 1649] µg/mL, p=0.001) and endoscopic remission (38 [15, 112] versus 328 [52, 2171] µg/mL, p=0.0002), compared with non-responders. The effects of post-induction calprotectin levels on clinical remission (β= -0.001, p=0.020) and endoscopic remission (β= -0.007, p=0.006) remained significant in multivariable models adjusted for age, sex, BMI, disease duration, and biological treatment. A cut point of 200 µg/mL post-induction was identified to predict endoscopic remission (sensitivity 92%, specificity 64%, ROC AUC 0.781) Conclusion High rates of clinical and endoscopic remission with biological therapies could be achieved in patients with ulcerative proctitis. Fecal calprotectin levels after the induction of biological therapies seem to predict the therapeutic response in patients with ulcerative proctitis

P879 Comparative Efficacy of Biologics and Small Molecule Therapies for the Induction and Maintenance of Endoscopic and Histological Remission in Ulcerative Colitis: A Systematic Review and Network Meta-analysis

Abstract Background Treatment options for moderate to severe ulcerative colitis (UC) are increasing rapidly, but lack of comparative efficacy trials make treatment choices a clinical challenge. We aimed to compare the relative efficacy of biologics and small molecules in achieving endoscopic and histological remission in patients with moderate to severe UC. Methods The literature was searched between January 1990 and July 2023. Phase 3 placebo or active comparator randomized controlled trials (RCTs) were included to assess the efficacy of biologics or small molecule drugs as induction or maintenance therapies for patients with UC. The primary outcome was induction and maintenance of endoscopic improvement (Mayo endoscopic score ≤1), whereas secondary outcomes were the induction and maintenance of endoscopic (Mayo endoscopic score = 0) and histological remission. Sub-analysis was performed based on previous exposure to biologic therapy. We used a random effects model and reported data as odd ratio (OR) with 95% confidence intervals (CIs). Results We identified 34 studies that met our inclusion criteria, with a total of 12,227 patients with UC. Upadacitinib was superior to most biologics in inducing endoscopic improvement and remission as well as maintaining endoscopic improvement and histological remission. Etrasimod ranked second, after upadacitinib, in maintenance of endoscopic improvement in both biologic naive (80.4%) and experienced (78.9%) patients. Infliximab was superior to adalimumab (OR 1.88, 95% CI, 1.07; 3.29) and vedolizumab (OR1.85, 95% CI, 1.13; 3.03) in inducing endoscopic improvement in overall UC patients. Filgotinib 200 mg (OR 4.76, 95% CI, 1.89; 5.88) and vedolizumab (OR 4.16, 95% CI, 2.94; 6.25) were superior to adalimumab in maintaining histological remission. In biologic naive patients, infliximab was found to be superior to adalimumab (OR 1.80, 95% CI, 1.05;3.07), vedolizumab (OR 5.20, 95% CI, 2.04;7.69), and golimumab (OR 6.30, 95% CI, 3.39;9.71) in inducing endoscopic improvement Conclusion Upadacitinib appears to be superior to other therapies in achieving both endoscopic improvement and remission as well as maintaining histological remission. Furthermore, etrasimod, filgotinib and tofacitinib ranked high in achieving these outcomes. This study highlights the role of small molecules drugs as effective alternatives to biologics.

P138 Novel serum markers for predicting disease activity in ulcerative colitis: results from a retrospective case-control study

Abstract Background Commonly used serum or faecal markers, such as C-reactive protein (CRP) and feacal calprotectin have several limitations and do not always correlate well with the degree of mucosal inflammation in the intestine as established by endoscopy. The aim of the current study was to evaluate the utility of a panel of serum markers (Visfatin, serum amyloid, LRG1, MMP-1, MMP-2, TFF3, Lipocalin-2 (NGAL), IL-6, IL-4, IL-7, IL-17) in predicting mucosal inflammation in ulcerative colitis(UC) patients. Methods We conducted an unmatched case-control retrospective study. Patients were selected consecutively, based on their enrollement date, from a prospective IBD cohort. We selected two groups of UC patients, each of them with active disease at baseline and different outcomes during follow-up: mucosal healing and persistant disease activity, as resulted from clinical and endoscopic evaluation. Inflammatory burden was investigated using the C-reactive protein and endoscopic activity was reported using the Mayo endoscopic score. Quality of life was also evaluated at each visit using The Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Clinical disease activity was quantified using the partial Mayo score. Clinical remission was defined as a partial Mayo score < 2. Endoscopic activity was assessed using the Mayo endoscopic score[i] . Mucosal healing was defined as Mayo endoscopic score of 0. The selection of investigated biomarkers was based on the results of a systematic review previously published by the research team [i] State M, Negreanu L, Voiosu T, Voiosu A, Balanescu P, Mateescu RB. Surrogate markers of mucosal healing in inflammatory bowel disease: A systematic review. World J Gastroenterol. 2021 Apr 28;27(16):1828-1840. doi: 10.3748/wjg.v27.i16.1828. Results 84 serum samples from 42 patients were retrospectively analyzed (21 patients with mucosal healing and 21 patients with persistant activity during follow-up). Lipocalin proved to be a reliable marker for the noninvasive assessment of endoscopic activity, with 90% sensitivity and 95% specificity at a cut-off level of 0,421μg/ml (AUROC 0,677). The combination of lipocalin, age, gender and BMI (Figure 1) is a good predictor of persistant activity during follow-up (AUROC 0.87, 95% CI, 0.762-0.979). Conclusion Our findings provide support for the use of lipocalin as a surrogate marker for mucosal inflammation. The combination of lipocalin, age, gender and BMI might be useful for guiding treatment and monitoring decisions.

P381 Intestinal ultrasound in newly diagnosed Ulcerative Colitis predicts the need for colectomy

Abstract Background Upon diagnosis of ulcerative colitis (UC), it remains challenging to predict who will have a severe disease course, ultimately necessitating colectomy. Predictive tools capable of risk-stratifying patients and individualize treatment are warranted. The aim of this study was to assess whether Intestinal ultrasound (IUS), performed at the onset of UC, could help predict the need for colectomy within the first year of diagnosis. Methods In a Danish prospective inception cohort, all new-onset adult patients with UC (including unclassified IBD) with left-sided or extensive colitis underwent IUS near the diagnostic endoscopy. The assessment included the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) and the bowel wall thickness (BWT) of the most inflamed segment. Besides IUS, we recorded age, gender, smoking, BMI, the Mayo endoscopic score (MES), the Simple Clinical Colitis Activity Index (SCCAI), and biomarkers hemoglobin (hgb), C-reactive protein (CRP), albumin and fecal calprotectin. Results During inclusion (May 2021 – April 2023), we included 193 UC patients with Montreal classification E2 or E3. In total, 12/193 (6%) underwent colectomy within the first year or during follow-up (min. 6 months). Baseline characteristics are presented in Table 1. Univariable analyses identified high MES, CRP, SCCAI, IBUS-SAS, and BWT, along with low Hgb and albumin, as significantly associated with an increased colectomy risk. Multivariable analysis with stepwise reduction identified only SCCAI (OR: 2.0, CI 1.2–3.3, p<0.005) and BWT (OR: 1.6, CI 1.1–2.3, p=0.01) as independent predictors. Through ROC analysis, BWT presented the highest accuracy (AUC: 0.89), and the optimal cut-off by Youden Index for colectomy prediction was > 6.1 mm. Combining all the significant non-IUS predictors, CRP, MES, SCCAI, hgb, and albumin yielded an AUC of 0.88. The highest accuracy was found by combining SCCAI and BWT, with an AUC of 0.94. Kaplan-Meier curve for colectomy-free survival is presented in Figure 1. Among patients with BWT>6.1mm, 18/21 (86%) started systemic steroids within the first week, compared to 43/125 (34%) of patients with BWT ≤ 6.1, p=0.007. Among patients with BWT > 6.1mm, 11/21 (52%) started biologics within the first 31 days, compared to 5/125 (4%) of patients with BWT≤6.1mm, p<0.001. Despite more aggressive treatment, 8/21 (38%) with BWT>6.1mm had a colectomy compared to 2/125 (2%) with BWT≤6.1mm.Conclusion IUS at UC onset, specifically BWT, is a robust predictor of colectomy risk within the first year of diagnosis. Combining clinical symptom scores with IUS enhances predictive accuracy. It can accurately identify patients at an increased risk of colectomy, guiding early treatment decisions for improved patient outcomes.

P962 Clinical and endoscopic remission at 3 months after Acute Severe Ulcerative Colitis is predictive of maintenance therapy outcomes at 12 months - Results from PREDICT UC

Abstract Background The optimal maintenance regimen after rescue therapy for Acute Severe Ulcerative Colitis (ASUC) is unknown. We aimed to evaluate prospectively the impact of different maintenance regimens after successful infliximab (IFX) rescue, along with factors associated with Month 12 remission. Methods Clinical responders at 3 months from PREDICT UC, a randomised trial (NCT02770040) comparing standard and intensified IFX rescue strategies, were evaluated in this prospective cohort study up to Month 12. Maintenance therapies were as follows: (1) Thiopurine monotherapy (azathioprine or mercaptopurine) for thiopurine naïve patients or prior suboptimal thiopurine therapy (TP); (2) Combination thiopurine and IFX therapy 5mg/kg 8-weekly for thiopurine-experienced patients (IFX+TP combo); (3) IFX monotherapy 5mg/kg 8-weekly for thiopurine-intolerant patients (IFX mono). All patients received oral 5-aminosalicylates. Clinical and endoscopic assessments were performed at baseline (Month 3) and Month 12. Clinical remission was defined as a partial Mayo score of 0-1 and endoscopic remission as Mayo Endoscopic Score (MES) of 0-1. Results Of 138 patients randomised, 79 entered the maintenance phase. Of these, 56 (71%) received TP, 16 (20%) received IFX+TP combo and 7 (9%) received IFX mono. Baseline characteristics were similar across the 3 maintenance groups. At 12 months, 42 patients (53%) were in clinical remission, 44 patients (56%) were in endoscopic remission, and one patient underwent colectomy. The 3 maintenance groups had similar rates of clinical remission (TP 55%, IFX+TP combo 56%, IFX mono 29%; P=0.39) and endoscopic remission (TP 55%, IFX+TP combo 56%, IFX mono 57%; P=0.99) at 12 months. Clinical Remission On univariable and multivariable analysis, no factors were associated with clinical remission at 12 months, including baseline CRP, albumin, partial Mayo score, MES, UCEIS or maintenance strategy. Endoscopic Remission Factors associated with endoscopic remission at 12 months included baseline partial Mayo score of 0 (OR 3.36, 95% CI 1.24-9.10, P=0.017), MES of 0-1 (OR 3.48, 95% CI 1.08-11.27, P=0.037) and UCEIS of 0-1 (OR 3.30, 95% CI 1.24-8.76, P=0.016). However, a partial Mayo score cut-off of 0-1 did not reach significance (OR 3.46, P=0.09). No factors associated with endoscopic remission were identified on multivariable analysis. Conclusion In steroid-refractory ASUC patients who received IFX rescue, clinical and endoscopic remission at Month 3 were associated with endoscopic remission at Month 12, particularly among patients with greater depth of remission. Month 3 assessment helps identify patients at higher risk of disease progression for whom more intensive treatment may be required.

P869 Deep ulcers in acute Ulcerative Colitis at index endoscopy predict corticosteroid resistance

Abstract Background Ulcerative Colitis (UC) is a chronic inflammatory disease affecting the colon. Its acute form can be life-threatening, necessitating hospital admission and intravenous (IV) corticosteroid treatment. This study aimed to predict IV corticosteroid response in acute UC patients based on endoscopic findings at admission. Methods Individuals admitted to the hospital for acute UC for intravenous corticosteroid treatment were selected. Those with gastrointestinal infections and those without endoscopy at admission were excluded. Results A retrospective analysis was conducted on a cohort of 62 patients, of which 25.8% did not respond to IV steroids. No significant associations were found between demographic, clinical, and laboratory parameters and corticosteroid response at admission. Rectosigmoidoscopy was performed for all patients upon hospitalization, and the Mayo Endoscopic Score (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) were obtained. The results revealed significant differences in median UCEIS scores between non-responders and responders (7, IQR 3 vs. 5, IQR 1, p=0.011). Notably, a UCEIS score of ≥5 demonstrated a sensitivity of 100% in identifying patients who did not respond to corticosteroids, although with a lower specificity of 22.7%. Furthermore, the MES exhibited a statistically significant association with treatment response (p=0.002), with a MES≤2 having a negative predictive value of 92.9% for IV steroid resistance. Importantly, the presence and type (small vs. large) of ulcers at the initial endoscopy were found to be the most effective predictive factor for corticosteroid response (AUC=0.745; 95%CI=0.594-0.896; p=0.005), as 57.1% of patients with deep ulcers were non-responders. Conclusion The importance of evaluating ulcer severity during endoscopic assessment in patients with acute ulcerative colitis is underscored by our findings. Notably, the presence of deep mucosal ulcerations should prompt consideration for intensifying therapy.

P487 Automated Scoring of Patient Endoscopy Videos Using Deep Learning Techniques: A Promising Approach for Clinical Trials in Inflammatory Bowel Disease

Abstract Background Accurate assessment of patient endoscopy videos is crucial for various clinical trials, including those related to inflammatory bowel diseases (IBD). However, manual scoring by trained local and central readers can lead to discrepancies, inconsistencies, and logistical challenges. To address these issues, we devised a novel approach utilizing deep learning techniques to automate the analysis, parsing, and scoring of patient endoscopy videos. Our objectives were to reduce human error/variability, accelerate endoscopic scoring by enhancing read accuracy, and lower clinical trial cost. Methods We developed and trained deep learning models using a large dataset of labeled patient endoscopy images. The models were designed to predict the Mayo endoscopic score (MES), which serves as a standardized measure of disease severity in IBD. Our approach developed convolutional neural networks (CNNs) to extract features from raw video data and processed them into meaningful patterns. The models were optimized using transfer learning and validated on external endoscopy video datasets through rigorous testing protocols. Results Using an iterative process, we developed two sets (total 4) of proof-of-concept (POC) Artificial Intelligence (AI) models using frame level datasets from endoscopy videos. First, quality was assessed by the blur detection model, currently performing at > 90% accuracy, and the bowel preparation model, performing at > 95% accuracy compared to the labels provided by human annotators. Second, MES sub-score prediction currently performs with >75% accuracy for 4-level Mayo sub-score prediction and >90% accuracy in predicting advanced MES scores (2 or higher compared with consensus score derived from 3 annotators). Conclusion The presented study highlights the potential of deep learning techniques in revolutionizing the assessment of patient endoscopy videos in clinical trials for IBD. Automating the endoscopic scoring process enables faster, more accurate, and cost-efficient evaluations, ultimately leading to better detection of patient outcomes. Future research directions involve further refining the models to enhance their performance and expand their application to other gastrointestinal diseases.

DOP11 Disease clearance after 16 weeks of treatment with vedolizumab in patients with moderate to severe Ulcerative Colitis: An interim analysis from the VERDICT trial

Abstract Background Disease clearance in ulcerative colitis (UC) is defined as concurrent achievement of clinical, endoscopic, and histologic remission.1 Regardless of the drug used in clinical trials, no more than 20% of patients reach disease clearance after 1 year; thus, it is a high bar to achieve with a potential for disease modification.2 VERDICT is a continuing, randomised, controlled trial (NCT04259138) with a primary objective of determining the optimal treatment target in moderately-to-severely active UC, by comparing target Group 1 (corticosteroid-free [CSF] symptomatic remission), target Group 2 (CSF symptomatic remission + endoscopic improvement), and target Group 3 (CSF symptomatic remission + endoscopic improvement + histologic remission). Patients follow treatment algorithms that feature early introduction of vedolizumab (VDZ) with no dose escalation before week 16 and no week 10 dosing. Here we report the achievement of CSF disease clearance at week 16 in Group 3. Methods CSF disease clearance was defined as achievement of a CSF Mayo rectal bleeding subscore=0 + endoscopic improvement (Mayo Endoscopic Score [MES] ≤1) + histologic remission (Geboes score <2B.0). VDZ 300 mg was administered intravenously following a treatment algorithm based upon baseline UC treatment until assigned treatment target was reached at week 16. Results are summarized overall and by bio-exposure status. Results As of 18 Aug 2023, 553 patients were enrolled in VERDICT with 253 assigned to target Group 3. The group had a mean age of 41.2 years (standard deviation [SD] 14.3), mean disease duration of 7.3 years (SD 7.8), and 42% were female (Table). In total, 216 (85%) were bionaïve, 159 (63%) had a baseline MES of 3, and 129 (51%) were receiving concomitant corticosteroids. Figure 1 shows the breakdown of the 253 patients. At time of analysis, remission target status was unavailable for 30 bionaïve and 11 bio-exposed patients. Among the 212 patients with observed data, 86 (41%) achieved CSF remission, including 77 (41%) of the 186 bionaïve patients with data and 9 (35%) of the 26 bio-exposed patients with data. Corresponding values of achieving CSF disease clearance in the intention-to-treat population were 34% (86/253), 36% (77/216), and 24% (9/37), respectively. All patients with disease clearance were receiving VDZ treatment from baseline. Conclusion At week 16, 41% of patients enrolled in the target group of CSF symptomatic remission + endoscopic improvement + histologic remission had achieved CSF disease clearance, with a numerically higher percentage in bionaïve compared to bio-exposed. References 1 D’Amico et al. Inflamm Bowel Dis. 2023 doi:10.1093/ibd/izad1592. 2 Colombel et al. Gastroenterol Hepatol. 2021;17:233

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.

P489 Systematic review and meta-analysis of the accuracy of computer-aided diagnosis in identifying endoscopic remission in Ulcerative Colitis

Abstract Background Endoscopic remission (ER), the absence of active inflammation during endoscopy, is a key therapeutic target in Ulcerative Colitis (UC). ER is assessed during colonoscopy using standardised scoring systems. However, there remains significant inter-operator variability in assessing ER, for which the application of computer-aided diagnosis (CADx) could be a potential solution. A previous systematic review and meta-analysis on this topic was limited to literature up to June 2022 and did not assess the methodological quality of studies or heterogeneity amongst results. We aimed to update this review. Methods Searches were performed on six electronic databases and relevant reference lists up to May 2023. Data was extracted and screened independently by two reviewers. Methodological assessment was performed using the QUADAS-2 tool. An ‘image selection’ domain was added to the tool given the importance of endoscopic image quality in training and testing data on CADx’s accuracy. Meta-analysis was performed using a bivariate model. Heterogeneity was assessed through visual inspection of forest plots and receiver-operating characteristic curves, subgroup analyses and meta-regression. The overall quality of evidence was assessed using GRADE methodology. Results 17 studies (16 full-text articles and one abstract) were identified. 15 studies adopted a cross-sectional design. All studies used expert endoscopists scoring of ER as the reference standard. The Mayo Endoscopic Score was the most commonly used scoring system (13/17). CADx assessed ER in real-time in one study, but was applied to images and videos obtained from previous endoscopic procedures in all other studies. Inception-v3 was the most common CADx system used (6/17). ‘Patient selection’ was the domain of greatest concern due to a considerable number of studies using images from the same public database and under-reporting participant characteristics. All studies had a low risk of bias (ROB) in the ‘image selection’ domain. One study was deemed overall high ROB, and two were deemed overall unclear ROB. Sensitivity analysis was performed by removing these studies and the abstract, and pooled estimates were obtained from the remaining 13 studies. CADx had a pooled sensitivity of 90.3% and specificity of 94.6% for diagnosing ER. The overall quality of evidence was moderate due to the failure of a significant proportion of studies to report sufficient participant characteristics. Conclusion There is moderate quality evidence that CADx has high sensitivity and specificity for diagnosing ER in pre-clinical studies. Further evaluation is required in randomised controlled trials to evaluate its efficacy in real-time and human-computer interactions.

P576 Fecal calprotectin could predict clinical and endoscopic response to ustekinumab therapy

Abstract Background Ustekinumab (UST) is one of the most used biologic drugs for the treatment of Crohn’s Disease (CD) and Ulcerative Colitis (UC). However, not all patients achieve clinical remission and even less mucosal healing. There is currently scarce knowledge about the early markers of therapeutic response in this setting, with particular regard to mucosal healing. The aim of this multicenter study was to evaluate the role of fecal calprotectin (FC) as early predictor of mucosal healing. Methods We enrolled consecutive patients with CD or UC treated with UST for at least 48 weeks at four referral centers in the last 5 years. Therapeutic response was evaluated in terms of clinical remission (defined as a Partial Mayo Score <2 for patients with UC and as Harvey Bradshaw Index <5 for patients with CD, without concomitant corticosteroid therapy) and mucosal healing (defined as a Mayo Endoscopic Score <2 for UC and as the disappearance of ulcers for CD). We collected clinical and demographic data, as well as fecal calprotectin (FC) and C-Reactive Protein (CRP) levels at baseline and at week 24. Results Among 196 patients enrolled (73 [37.2%] women), 167 were affected by CD, whereas 29 by UC. Globally, 128 (65.3%) patients achieved clinical remission and 83 (42.3%) endoscopic remission at 48 weeks of treatment. There were no group differences in age, sex, BMI, baseline clinical and endoscopic indexes, or baseline CRP levels between patients achieving or not either clinical or endoscopic remission. Baseline calprotectin levels were lower in patients who achieved endoscopic remission (median [interquartile range] 391 [103, 1050] versus 825 [317, 1800] µg/mL,p=0.002). At week 24, lower calprotectin levels were observed in both the groups who achieved clinical (160 [50, 426] versus 439 [146, 1000] µg/mL,p<0.0001) and endoscopic remission (114 [43, 265] versus 392 [139, 912] µg/mL,p<0.0001) compared with non-responders. The effects of week-24 calprotectin levels on clinical remission (β= -0.003,p<0.0001) and endoscopic remission (β= -0.004,p<0.0001) remained significant in multivariable models adjusted for age, sex, and BMI. A cut-point of 268 µg/mL was identified as the optimal threshold of week-24 calprotectin for predicting clinical remission (sensitivity 65%, specificity 67%, ROC AUC 0.689), while a cut-point of 309 µg/mL was identified to predict endoscopic remission (sensitivity 79%, specificity 59%, ROC AUC 0.712). Conclusion Our data suggest that FC assessment after 24 weeks of treatment with UST could represent a promising early marker of response, even in terms of mucosal healing, in both CD and UC.