Mayo Endoscopic Score Research Articles

S15 Efficacy of Ozanimod in Patients With Ulcerative Colitis Who Were Previously Exposed to Vedolizumab: True North Post Hoc Analysis

Background: Ozanimod, an oral S1P receptor modulator that prevents lymphocyte migration to inflamed tissues, is approved for the treatment of moderate to severe ulcerative colitis (UC) in the US and EU. The phase 3 True North (TN) randomized trial showed that ozanimod was effective and well tolerated. Ozanimod efficacy in patients exposed to vedolizumab (VDZ-exp), an integrin receptor antagonist that interferes with lymphocyte trafficking to the gut, has not yet been described. This post hoc analysis of TN examined ozanimod efficacy in VDZ-exp patients. Methods: In TN, patients were randomized to oral once-daily ozanimod 0.92 mg or placebo (Cohort 1) or to open-label ozanimod (Cohort 2) during the induction period (IP). Patients with a clinical response to ozanimod at Week (W) 10 were rerandomized to ozanimod or placebo in the maintenance period (MP). Efficacy at W10 (IP) and W52 (MP) in the VDZ-exp subgroup was calculated. Differences in proportions between ozanimod and placebo at W10 were based on the Cochran-Mantel-Haenszel (CMH) test, stratified by corticosteroid use at screening and prior anti-TNF use. Differences between ozanimod/ozanimod and ozanimod/placebo at W52 were based on the CMH test stratified by remission status and corticosteroid use at W10. Results: TN included 185 VDZ-exp patients (Cohort 1: placebo, n=35; ozanimod, n=63; and Cohort 2: ozanimod, n=87). Baseline demographics and clinical characteristics were balanced across treatment groups. In the VDZ-exp subgroup, 52% of patients had extensive disease at baseline, 78% had a Mayo endoscopic score of 3, 85% were previously exposed to anti-TNF, and 61% were receiving corticosteroids at baseline. At W10, ozanimod (Cohort 1) was numerically more effective vs placebo for all endpoints in VDZ-exp patients: symptomatic remission (15.9% vs 8.6%), clinical remission (4.8% vs 2.9%), clinical response (28.6% vs 20.0%), endoscopic improvement (Mayo endoscopic score [MES] ≤1; 12.7% vs 5.7%), and mucosal healing (histologic endoscopic mucosal improvement [HEMI]; 6.3% vs 0%). Notably, in the subgroup previously exposed to VDZ as a first-line advanced therapy, clinical response at W10 was achieved in 50% (6/12) and 42% (5/12) of ozanimod patients in Cohorts 1 and 2, respectively. In the subgroup previously exposed to VDZ and other biologics, clinical response at W10 was achieved in 23.5% (12/51) and 32.0% (24/75) of ozanimod patients in Cohorts 1 and 2, respectively. At W52, a higher proportion of VDZ-exp patients on continuous ozanimod achieved all efficacy endpoints vs the ozanimod/placebo group, with significant differences shown for most endpoints: symptomatic remission = 54.5% vs 13.6% (P=0.003); clinical remission = 39.4% vs 4.5% (P=0.005); clinical response = 57.6% vs 22.7% (P=0.014); endoscopic improvement (MES ≤1) = 39.4% vs 9.1% (P=0.017); mucosal healing (HEMI) = 21.2% vs 0% (P= nonestimable); corticosteroid-free remission = 27.3% vs 4.5% (P=0.044), respectively. Ozanimod/ozanimod vs ozanimod/placebo differences at W52 were larger than ozanimod vs placebo differences at W10. Conclusion(s): This post hoc analysis of the phase 3 TN study found that ozanimod was effective in UC patients who were previously VDZ-exp, including those who failed VDZ alone or following other advanced therapies. Future studies evaluating ozanimod in VDZ-exp patients are warranted.

S9 Endoscopic Scores as Predictors of Treatment Failure in Ulcerative Colitis

Background: The endoscopic Mayo score (MS) is the most frequent score used for the evaluation of inflammatory activity in Ulcerative Colitis (UC), varying from 0 to 3 points. Recently the DUBLIN score (DS) emerged, which varies from 0 to 9 points and results from the product of the MS and the disease extent, according to Montreal classification, E1-E3. In this study we aimed to evaluate and compare the predictive ability of MS and DS for long term treatment failure. Methods: A retrospective and unicentric study was conducted, including patients with left-sided or extensive UC, asymptomatic and without the need for steroid therapy or therapy changes in the 6 months prior to undergoing total colonoscopy with calculation of MS and DS. Treatment failure was evaluated, defined by the need for therapy changes and/or hospitalization because of disease exacerbation, over a follow-up period of a minimum of 24 months and a maximum of 84 months. Results: A total of 204 patients were included, 104 (51%) females and with a mean age at diagnosis of 36.4 ± 12.7 years. In the initial evaluation, 48 (23.5%) were being treated with anti-TNFα medication. The mean values of MS were 1.0 ± 1.1 points and of DS were 2.2 ± 2.6 points. During follow-up, 32 (15.7%) patients experienced treatment failure and patients initially treated with anti-TNFα medication had 2.3 times higher risk of treatment failure (P = 0.042). MS values (AUC 0.809; P < 0.001; with sensitivity of 0.938 and specificity of 0.529 for values equal or superior to 1) and DS values (AUC 0.789; P < 0.001; with sensitivity of 0.844 and specificity of 0.581 for values equal or superior to 2) had good discriminative abilities in predicting treatment failure. There were no statistically significant differences in the discriminative ability between both scores (P = 0.340). Conclusion(s): MS and DS had good discriminative abilities in predicting treatment failure. However, the integration of the disease extent in the DS as a complement of MS in the evaluation of UC was not associated with a higher predictive ability of long term treatment failure.

CO11 Comparison of Relapse Rates in Ulcerative Colitis Patients With Mayo Endoscopic Score of 0 or 1: Systematic Literature Review and Meta-Analysis

Endoscopic improvement (Mayo Endoscopic Sub score-MES 0 or 1) and endoscopic remission (Mayo Endoscopic Sub score 0) are recognized as important treatment endpoints in ulcerative colitis (UC). The objective of this analysis was to compare relapse rates in UC patients with MES of 0 or 1.

S121 Ozanimod in Ulcerative Colitis: A Tertiary Care Center’s Experience Over One Year

Background: It is estimated that the prevalence of ulcerative colitis (UC) in the United States is 465 per 100,000 people, with its incidence projected to increase further in the upcoming years. Although the advent of biologics has revolutionized UC therapeutics, a substantial proportion of patients suffer from refractory disease. Ozanimod is an oral sphingosine-1-phosphate receptor modulator that has been recently approved by the US Food and Drug Administration for moderate to severe UC therapy. Real-world experience with ozanimod in UC remains to be defined. The aim of this study is to evaluate the safety and efficacy of ozanimod in patients with UC at a tertiary medical center. Methods: We performed a retrospective chart review of patients with UC treated with ozanimod within the MedStar health system between June 2021 to June 2022. The following inclusion criteria were applied: individuals 18 years or older, histological diagnosis of UC, and initiated on ozanimod at a MedStar Gastroenterology site. Results: Eight patients with UC (mean age = 35.5 years; 50% women; mean disease duration = 12.4 years; 63 percent pancolitis, 25 percent proctosigmoiditis, 13 percent left-sided colitis) were identified and included in this study, all of whom were seen at MedStar Georgetown University Hospital. Baseline disease characteristics: mean Mayo Endoscopic Score = 2.4, mean CRP = 9.8 μg/g, and mean Fecal Calprotectin = 1276 μg/g. All patients had previously failed treatment with at least one biologic agent. Following ozanimod initiation, one patient entered clinical remission, 3 patients showed improvement in UC symptoms, 3 patients showed no improvement or worsening of UC symptoms (including one who had total colectomy within 10 days of initiation), and one patient discontinued ozanimod use due to relocating abroad. After a mean follow-up time of 4 months post-ozanimod initiation, patients had the following disease characteristics: mean CRP = 14.4 μg/g, and mean Fecal Calprotectin = 912.5 μg/g. Patients treated with ozanimod reported adverse events such as fatigue (n = 4), eye irritation (n = 3), joint pain (n = 2), nausea and vomiting (n = 2), shortness of breath (n = 1), chest pain (n = 1), and brain fog (n = 1). One patient discontinued ozanimod due to adverse events potentially related to ozanimod. Conclusion(s): Ozanimod is well-tolerated with minimal side effects in patients with UC. The overall clinical response to ozanimod was variable; however, most patients experienced improvement in UC symptoms. Considering that all patients had previously failed at least one biologic therapy, our experience indicates that ozanimod is effective in improving symptoms and inducing remission in patients with refractory disease. Future studies with a larger sample and extended follow-up period are warranted to define the efficacy and time to remission of ozanimod in UC patients.

Improving the Computer-Aided Estimation of Ulcerative Colitis Severity According to Mayo Endoscopic Score by Using Regression-Based Deep Learning.

Assessment of endoscopic activity in ulcerative colitis (UC) is important for treatment decisions and monitoring disease progress. However, substantial inter- and intraobserver variability in grading impairs the assessment. Our aim was to develop a computer-aided diagnosis system using deep learning to reduce subjectivity and improve the reliability of the assessment. The cohort comprises 11 276 images from 564 patients who underwent colonoscopy for UC. We propose a regression-based deep learning approach for the endoscopic evaluation of UC according to the Mayo endoscopic score (MES). Five state-of-the-art convolutional neural network (CNN) architectures were used for the performance measurements and comparisons. Ten-fold cross-validation was used to train the models and objectively benchmark them. Model performances were assessed using quadratic weighted kappa and macro F1 scores for full Mayo score classification and kappa statistics and F1 score for remission classification. Five classification-based CNNs used in the study were in excellent agreement with the expert annotations for all Mayo subscores and remission classification according to the kappa statistics. When the proposed regression-based approach was used, (1) the performance of most of the models statistically significantly increased and (2) the same model trained on different cross-validation folds produced more robust results on the test set in terms of deviation between different folds. Comprehensive experimental evaluations show that commonly used classification-based CNN architectures have successful performance in evaluating endoscopic disease activity of UC. Integration of domain knowledge into these architectures further increases performance and robustness, accelerating their translation into clinical use.

Improvement of ulcerative colitis control by searching and restricting of inflammatory trigger factors in daily clinical practice.

Exacerbating factors of ulcerative colitis (UC) are multiple and complex with individual influence. We aimed to evaluate the efficacy of disease control by searching and restricting inflammation trigger factors of UC relapse individually in daily clinical practice. Both patients with UC history or new diagnosis were asked to avoid dairy products at first doctor visit. Individual-reported potential trigger factors were restricted when UC flared up (Mayo endoscopy score ≥1) from remission status. The remission rate, duration to remission and medication were analyzed between the groups of factor restriction complete, incomplete and unknown. The total remission rate was 91.7% of 108 patients with complete restriction of dairy product. The duration to remission of UC history group was significantly longer than that of new diagnosis group (88.5 days vs. 43.4 days, P=0.006) in patients with initial endoscopic score 2-3, but no difference in patients with score 1. After first remission, the inflammation trigger factors in 161 relapse episodes of 72 patients were multiple and personal. Milk/dairy products, herb medicine/Chinese tonic food and dietary supplement were the common factors, followed by psychological issues, non-dietary factors (smoking cessation, cosmetic products) and discontinuation of medication by patients themselves. Factor unknown accounted for 14.1% of patients. The benefits of factor complete restriction included shorter duration to remission (P<0.001), less steroid and biological agent use (P=0.022) when compared to incomplete restriction or factor unknown group. Restriction of dairy diet first then searching and restricting trigger factors personally if UC relapse can improve the disease control and downgrade the medication usage of UC patients in daily clinical practice.

Development of a Core Outcome Set for Real-world Data in Inflammatory Bowel Disease: A European Crohn's and Colitis Organisation [ECCO] Position Paper.

The utility of real-world data is dependent on the quality and homogeneity of reporting. We aimed to develop a core outcome set for real-world studies in adult patients with inflammatory bowel disease [IBD]. Candidate outcomes and outcome measures were identified and categorised in a systematic review. An international panel including patients, dietitians, epidemiologists, gastroenterologists, nurses, pathologists, radiologists, and surgeons participated in a modified Delphi consensus process. A consensus meeting was held to ratify the final core outcome set. A total of 26 panellists from 13 countries participated in the consensus process. A total of 271 items [130 outcomes, 141 outcome measures] in nine study domains were included in the first-round survey. Panellists agreed that real-world studies on disease activity should report clinical, endoscopic, and biomarker disease activity. A disease-specific clinical index [Harvey-Bradshaw Index, Partial Mayo Score, Simple Clinical Colitis Activity Index] should be used, rather than physician global assessment. In ulcerative colitis [UC], either the UC Endoscopic Index of Severity or the Mayo Endoscopic Score can be used, but there was no consensus on an endoscopic index for Crohn's disease, nor was there consensus on the use of the presence of ulcers. There was consensus on using faecal calprotectin and C-reactive protein. There was no consensus on the use of histology in real-world studies. A core outcome set for real-world studies in IBD has been developed based on international multidisciplinary consensus. Its adoption will facilitate synthesis in the generation of real-world evidence.

S863 Impact of Race on ANTI-TNF Immunogenicity in Patients with Inflammatory Bowel Disease

Introduction: Immunogenicity is a major contributor to anti-tumor necrosis factor (anti-TNF) treatment failure in inflammatory bowel disease (IBD). Immunomodulator and anti-TNF combination therapy is associated with a decreased risk of immunogenicity. Anti-TNF immunogenicity was recently linked to HLA-DQA1*05 genotype. This study aims to determine the impact of race on rates of immunogenicity and treatment outcomes of IBD pts on anti-TNF combination therapy. Methods: This was a single-center, retrospective study of IBD pts who have been treated with immunomodulators and anti-TNF combination therapy between 2012 and 2020. Our primary outcomes were the rates of anti-TNF antibody formation and mean anti-TNF drug levels between Caucasian group(CG) and non-Caucasian group(NCG) on combination therapy. Secondary outcomes included steroid-free clinical remission (SFCR), endoscopic remission (ER) (absence of ulcers/erosions in CD and Mayo endoscopic score ≤ 1 for UC), & normal serum C-reactive protein (CRP) (defined as ≤ 5. mg/L). Continuous variables were analyzed using unpaired student’s t-test. Categorical variables were analyzed using a chi-square test. Results: A total of 124 pts were included (CD; 68.5%, UC; 27.4%, indeterminate colitis; 3.2%, pouchitis; 0.9%). The median age was 32 years (range 13-69), and 54.8% were male. A total of 87 pts were on infliximab & 37 pts were on adalimumab. Combination therapy with thiopurine was employed in 87.1% while 12.9% were on methotrexate. A total of 85 pts were self-identified as Caucasian. There were no significant differences between CG vs NCG in terms of baseline and disease characteristics (Table). Anti-TNF antibody formation was observed in 32.9% of pts in the CG, and 20.5% of pts in the NCG (p=0.16). Mean anti-TNF drug levels were lower in the CG at 15.4 ± 14.5 µg/mL vs. the NCG at 22.7 ± 15.1 µg/mL (p=0.01). SFCR was observed in 61.2% vs. 58.9% (p=0.82) in CG vs. NCG, respectively. In CG 42.4% vs. 33.3% in NCG (p=0.34) discontinued anti-TNF treatment during follow-up. ER was observed in 45.9 % vs 51.3% (p=0.44), and normal CRP was observed in 51.8% vs. 58.9% (p=0.28) in CG vs. NCG, respectively. Conclusion: In our cohort, Caucasian pts on anti-TNF combination therapy for IBD had significantly lower anti-TNF drug levels as compared to the non-Caucasian group. However, there was no significant difference between rates of anti-TNF antibody formation and clinical outcomes between the groups. Larger studies are needed to clarify impact of race on anti-TNF therapy. Table 1. - Comparison of Characteristics Between Caucasian vs. Non-Caucasian Race Caucasian (n=85), n (%), mean (SD) Non-Caucasian (n=39), n (%), mean (SD) P-value 34.7 (13.7) 34.7 (11.7) 0.98 47 (55.3) 21 (53.9) 0.88 7 (8.2) 6 (15.4) 0.23 36.4 (27.1) 41.9 (31.8) 0.35 0.07 53 (62.4) 32 (82.1) 29 (34.1) 5 (12.8) 2 (2.3) 2 (5.1) 1 (1.2) 0 21 (24.7) 15 (38.5) 0.12 24 (28.2) 14 (35.9) 0.81 10 (11.8) 6 (15.4) 0.77 61 (71.8) 26 (66.7) 0.56 69 (81.2) 29 (74.4) 0.39 12.5 (21.4) 6.8 (7.6) 0.15 3.9 (0.6) 4.1 (0.4) 0.16 *Data missing for 68 patients.**Data missing for 42 patients.Abbreviations: Anti TNF, anti-tumor necrosis factor; CRP, C reactive protein.

S945 Diagnostic Accuracy of Convolutional Neural Network-Based Machine Learning Algorithms in Endoscopic Severity Prediction of Ulcerative Colitis: A Systematic Review and Meta-Analysis

Introduction: Endoscopic severity of ulcerative colitis (UC) predicts clinical outcomes and is essential to guide treatment and evaluate therapeutic response. The Mayo endoscopic score (MES) is commonly used to objectively classify mucosal damage. It ranges from 0 to 3, with a higher score reflecting increased severity. With advances in machine learning, artificial intelligence is being employed for automating image analysis. Convolutional neural network (CNN) is a powerful deep learning method for image recognition, and in this study, we aim to look at diagnostic accuracy parameters of CNN based machine learning algorithms to predict UC severity. Methods: Multiple databases, including Medline, Scopus, and Embase, were searched from inception to May 2022 using specific terms for studies evaluating the diagnostic accuracy parameters of machine learning algorithms in assessing UC severity. Inclusion was restricted to studies that employed CNN based algorithms. Outcomes of interest were the pooled accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Multiple 4X4 contingency Tables assessing the diagnostic accuracy of the algorithms were considered independent of each other as the goal was to study the overall direction of pooled rates and not calculate precise point estimates. Standard meta-analysis methods were employed using the random-effects model, and heterogeneity was assessed using the I2 statistics. Results: 12 studies were included that exclusively used CNN algorithm. Studies that used support vector machines or a combination were excluded. The CNN algorithm was trained and tested to predict Mayo score severity 0, 1, 2 & 3, individually in majority of the studies. In few studies the CNN algorithm was used to differentiate between Mayo 0 vs 1, and Mayo 0-1 vs 2-3. Although, 'ground-truth' differed, individual 4X4 Tables were considered as independent of each other for the purpose of this study. The pooled rate were as follows: Accuracy 91.2% (95% CI; 87.4-93.9, I2=84%), sensitivity 83.9% (79.2-87.7, 89%), specificity 82.3% (89.5-94.4, 84%), PPV 86.5% (980.7-90.8, 89%) and NPV 89.4% (85.8-92.2, 78%) (Figure). Conclusion: Based on our meta-analysis of 12 studies, CNN-based machine learning algorithms demonstrated excellent pooled diagnostic accuracy parameters. Further work seems to be needed to get the NPV >90. Future well-controlled studies are warranted to establish its clinical use in comparison to endoscopists’ assessment of colonoscopic UC severity (Table).Figure 1.: Forest Plot for sensitivities of selected studies Table 1. - Pooled rates of outcomes of interest Outcome Pooled rates (95% confidence interval, I2 % heterogeneity) Accuracy 91.2% (87.4-93.9, 84%)20 datasets Sensitivity 83.9% (79.2-87.7, 89%)30 datasets Specificity 92.3% (89.5-94.4, 84%)30 datasets PPV 86.5% (80.7-90.8, 89%)18 datasets NPV 89.4% (85.8-92.2, 78%)18 datasets

S2772 Subcutaneous Sweet Syndrome Successfully Treated With Ustekinumab in Patient With Ulcerative Colitis

Introduction: Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) are well-established. Sweet syndrome (SS), or acute febrile neutrophilic dermatosis, is a reactive mucocutaneous manifestation of IBD presenting as erythematous papules/plauqes with associated fever and arthomyalgias. There is limited evidence regarding efficacy of Ustekinumab in management of EIMs of UC, particularly SS. Case Description/Methods: The patient is a 50-year-old woman with left-sided UC (Montreal classification E2) that previously failed several therapies, including mesalamine, azathioprine, infliximab, adalimumab, vedolizumab, and a fecal microbiota transplant trial. She presented with worsening abdominal pain, diarrhea/hematochezia, and bilateral lower extremity pain. She was febrile and tachycardic with tender, violaceous, and ulcerated subcutaneous nodules on the bilateral ankles with hemorrhagic bullae (FigureA). Labs revealed negative C. diff, elevated ESR/CRP, thrombocytosis, and borderline leukocytosis with neutrophilic predominance. Lower extremity MR imaging and bone biopsy revealed multifocal sterile osteomyelitis with adjacent abscess; skin biopsy demonstrated dense granulomatous/neutrophilic infiltrate in the deep dermis/subcutis without microorganisms, consistent with subcutaneous SS (FigureB). A restaging colonoscopy demonstrated severe proctosigmoid ulcerative colitis (FigureC). Given that the patient had failed several immunomodulators and biologic therapies, she was started on prednisone and Ustekinumab. Four months later, she reported complete resolution of her cutaneous SS off steroids and improving UC symptoms (less frequent and more formed stools, minimal hematochezia). Repeat MRI demonstrated resolution of the sterile osteomyelitis and abscess. Discussion: Our case highlights the novel use of Ustekinumab in the treatment of subcutaneous SS with sterile osteomyelitis in a patient with flaring UC. SS is a neutrophilic dermatosis that is a rare EIM of IBD, classically characterized by tender cutaneous lesions. There is limited evidence supporting the use of Ustekinumab in treating EIMs of CD, and a lack of data regarding its efficacy in treating EIMs of UC. Our case fills a major gap in the literature and highlights the clinical efficacy of Ustekinumab for SS and UC especially in patients that have a contraindication to, failed previous treatment with, or otherwise cannot tolerate corticosteroids and TNF-alpha antagonists.Figure 1.: 1A. Right lateral malleolus with 2.5 cm shallow erosion with slightly violaceous borders and central bright yellow fibrinous debris. There was slight atrophy of surrounding skin with mild edema and hyperpigmentation (left image). Left medial malleolus/dorsal foot with grouped irregular shallow ulcers with surrounding mild violaceous erythema (middle and right image). 1B. Left ankle biopsies showed mixed septal and lobular panniculitis with granulomatous and neutrophilic inflammation. Histologic sections show a mildly spongiotic epidermis with dense granulomatous and neutrophilic inflammatory infiltrate in the deep dermis and subcutis (left image). The inflammatory infiltrate, which consists of prominent neutrophils, histiocytes, and scattered lymphocytes, surrounds vascular and adnexal structures, as well as adipocyte lobules. Definitive features of vasculitis are not seen. PASd (periodic acid-Schiff-diastase), GMS (Grocott’s methenamine silver), Gram, and Fite staining fail to highlight microorganisms (right image). 1C. Colonoscopy demonstrated severe (Mayo Endoscopy Score 3) proctosigmoid ulcerative colitis to 30 cm (left image). Sigmoid biopsies showed significant immune cell infiltration with crypt architectural distortion concerning for severe chronic active colitis. No evidence of granulomas, dysplasia or cytomegalovirus (right image).

S720 Endoscopic Severity Score of Immune-Mediated Colitis Is More Effective in Guiding Medical Treatment Than Clinical Severity Grade

Introduction: Endoscopic scoring systems have not been established for immune-mediated colitis (IMC). Previous studies have shown benefits from early endoscopic evaluation, but the value of endoscopy compared to clinical assessment remains uncertain. This study aims to establish an endoscopic scoring system for IMC and explore its utility in predicting the need for selective immunosuppressive therapy (SIT, infliximab or vedolizumab) compared to clinical symptoms severity. Methods: This is a retrospective study from 14 centers worldwide including 674 patients with IMC who underwent endoscopic valuation. Ten total endoscopic features were recorded based on endoscopic reports and assigned one point each (erythema, edema, loss of vasculature, friability, erosions, exudate, any ulcers, large ulcers, deep ulcers, ≥ 2 ulcers). The scoring system was devised by measuring the specificity of a selected score cutoff in predicting the need for SIT based on clinical consensus from the study group. IBM SPSS Statistics 26 was used to calculate specificities, Pearson correlations, and generate ROC curves (Figure). Results: We divided the cohort to include a training set and a validation set. In the training set, an endoscopy score (ES) cut-off ≥4 has a specificity of 82.8% across all colitis grades and 96.4% among grade 1 colitis alone to predict SIT use. A cut-off ≥5 showed a specificity of 87.6% and 98.2% respectively. These specificities were comparable to those of the validation sets. In contrast, clinical colitis and diarrhea grading based on Common Terminology Criteria for Adverse Events (CTCAE) was poorly associated with future SIT use (specificities of 27.4% and 12.3% respectively). Moreover, this new scoring system with a cutoff of 4-5 had a numerically higher specificity to a Mayo Endoscopic Score (MES) of 3 when ulcer was a mandatory factor (85%-88.2% vs 74.6%). Early endoscopic evaluation in disease course was associated with early SIT use (p< 0.001, r=0.4084). (Table) Conclusion: This is the largest, multi-center study to devise an endoscopic scoring system highlighting the important value of endoscopy in guiding the management of IMC for the first time. The results demonstrated that an ES cutoff ≥4 can achieve a higher specificity in predicting SIT use than clinical symptom grading alone. This study supports early and thorough endoscopic evaluation for IMC and paves the way for future external validation of the described scoring system.Figure 1.: ROC curves Table 1. - Specificity of prediction for selective immunosuppressant therapy use (infliximab and/or vedolizumab) by using endoscopy score cutoff 4 and 5 All colitis grades Colitis CTCAE grade 1 only Training set(N=337) Validation set (CI)(N=337) Training set(N=84) Validation set (CI)(N=66) Specificity(score cutoff 4) 82.8% 74.5% (68.5%, 80.3%) 96.4% 91.1% (82.2%, 97.9%) Specificity(score cutoff 5) 87.6% 83.0% (77.8%, 88.3%) 98.2% 93.3% (85.1%, 100%) Specificity of prediction for selective immunosuppressant therapy use (infliximab and/or vedolizumab) by using CTCAE grade of diarrhea and colitis CTCAE grade Patients Specificity Colitis CTCAE grade 1 vs 2-5 All patients (N=666) 27.4% Diarrhea CTCAE grade 1 vs 2-5 All patients (n=619) 12.3% Colitis grade 1 only N=136 18.1% Colitis grade 2-5 only, N=477 10.3% CTCAE: Common Terminology Criteria for Adverse Events.

Intestinal Ultrasound to Assess Ulcerative Colitis Disease Activity in Children: External Validation and Comparison of 2 Intestinal Ultrasound Activity Indices.

There is currently no consensus on the definition of an abnormal intestinal ultrasound (IUS) for children with ulcerative colitis (UC). This cross-sectional study aimed to externally validate and compare 2 existing IUS indices in children with UC. Children undergoing colonoscopy for UC assessment underwent IUS the day before colonoscopy, assessed with the Mayo endoscopic subscore. The UC-IUS index and the Civitelli index were compared with the Mayo endoscopic score in the ascending, transverse, and descending colon. The area under the receiver-operating characteristic curve for detecting a Mayo endoscopic score ≥2 of both scores was compared and sensitivity and specificity were calculated. A total of 35 UC patients were included (median age 15 years, 39% female). The area under the receiver-operating characteristic curve was higher for the UC-IUS index in the ascending colon (0.82 [95% confidence interval (CI), 0.67-0.97] vs 0.76 [95% CI, 0.59-0.93]; P = .046) and transverse colon (0.88 [95% CI, 0.76-1.00] vs 0.77 [95% CI, 0.60-0.93]; P = .01). In the descending colon, there was no difference (0.84 [95% CI, 0.70-0.99] vs 0.84 [95% CI, 0.70-0.98]). The optimal cutoff for the UC-IUS was <1 point to rule out a Mayo endoscopic score ≥2 (sensitivity: 88%, 100%, and 90% in the ascending, transverse, and descending colon, respectively) and a Mayo endoscopic score ≥2 could be detected using a cutoff of >1 (specificity: 84%, 83%, and 87%, respectively). For the Civitelli index, in our cohort, the optimal cutoff was <1 to rule out a Mayo endoscopic score ≥2 (sensitivity 75%, 65%, and 80%, respectively) and a cutoff >1 to detect a Mayo endoscopic score ≥2 (specificity 89%, 89%, and 93%, respectively). In this cohort, the UC-IUS index performed better than the Civitelli index. The UC-IUS index had both a high sensitivity and specificity in this cohort, when using 1 point as cutoff for a Mayo endoscopic score ≥2.

Endocytoscopy for assessing histologic inflammation in ulcerative colitis: development and prospective validation of the ELECT (ErLangen Endocytoscopy in ColiTis) score (with videos)

Apart from endoscopic healing as an established treatment goal in patients with inflammatory bowel disease (IBD), histologic remission is an emerging endpoint that might even better predict disease outcome, especially in ulcerative colitis (UC). Within this study, we aimed to evaluate whether endocytoscopy (EC) as an invivo contact microscopy technology can accurately assess histologic inflammation and predict the further course of disease in UC patients. Initially, a new and intuitive EC score reflecting the entire spectrum of microscopic disease activity in UC was consensually developed. Subsequently, this score was independently validated in 46 patients with UC who underwent close-meshed follow-up during which major adverse outcomes (MAOs; defined as disease flare, IBD-related hospitalization, IBD-related surgery, necessity for initiation or escalation therapy) were recorded. Results of EC grading of inflammatory activity were compared against 2 validated histologic scores in UC. Diagnostic performance of endoscopic remission under white-light endoscopy (Mayo Endoscopic Score and Ulcerative Colitis Endoscopic Index of Severity), EC, and histology were compared for the prediction of MAOs. Endocytoscopic assessment of inflammatory activity in UC based on the newly developed ErLangen Endocytoscopy in ColiTis score showed strong correlation with histopathologic scoring (Robarts Histopathology Index, r= .70; Nancy Histologic Index, r= .73) and was superior to white-light endoscopy for grading of microscopic disease activity, with a sensitivity of 88%, specificity of 95.2%, and area under the curve of .916. Furthermore, EC exhibited a high interobserver agreement for invivo grading of microscopic inflammation and was comparably accurate as histopathology for forecasting the occurrence of MAOs in UC. Endocytoscopic grading of inflammatory activity along a newly developed scoring system enabled real-time histology in UC patients and better predicted clinical outcome in UC patients than endoscopic remission.

Oral beclomethasone dipropionate is an effective treatment for immune checkpoint inhibitor induced colitis

IntroductionSystemic corticosteroids are the mainstay of treatment for immune checkpoint inhibitor induced (CPI) colitis but are associated with complications including life-threatening infection. The topically acting oral corticosteroid beclomethasone dipropionate (BD)...

Ulcerative colitis: Impact of early disease clearance on long-term outcomes - A multicenter cohort study.

BackgroundClinical remission and endoscopic mucosal healing are the main treatment targets in patients with ulcerative colitis (UC). Recently, the concept of disease clearance has been proposed as a potential target in UC.ObjectiveWe aimed to evaluate the impact of disease clearance on long‐term outcomes in UC patients.MethodsA multicenter retrospective cohort study was conducted at the Humanitas Research Hospital‐IRCCS (Italy) and at the Nancy University Hospital (France) between 2014 and 2021. Disease clearance in UC was defined as simultaneous clinical (partial‐Mayo score ≤2), endoscopic (endoscopic‐Mayo score = 0), and histological (Nancy index = 0) remission, and patients were monitored over a long‐time follow‐up (≥12 months), to compare the occurrence of negative outcomes.ResultsA total of 494 patients with UC was included in the study (269, 54.4% males). Disease clearance was present in 109 patients (22.1%) at baseline. Median follow up was 24 months. Patients with disease clearance were associated to a significantly lower risk of UC‐related hospitalization compared with the control group (5.5% vs. 23.1%; p < 0.001) at last observation. Similarly, a lower rate of surgeries was detected in patients with disease clearance at baseline compared with those without (1.8% vs. 10.9%; p = 0.003). The Kaplan Meier curves confirmed that patients with disease clearance at baseline had a lower risk of hospitalization (log‐rank p < 0.0001) and surgery (log‐rank p < 0.00095).ConclusionIn UC patients with early disease clearance are at significant lower risk for hospitalization and surgery. Disease clearance should be considered as a new composite outcome.

Predictors of Placebo Induction Response and Remission in Ulcerative Colitis

High placebo response rates in clinical trials of ulcerative colitis (UC) have been reported previously. However, data from patient-level analyses are lacking. We assessed factors associated with clinical and endoscopic placebo response among placebo-treated patients in clinical trials of UC. We performed a post hoc analysis of pooled clinical trial data from GEMINI-1, ACT-1, ACT-2, PURSUIT, ULTRA-2, OCTAVE-1, and OCTAVE-2. Predictors were assessed in placebo-treated patients for their association with end of induction (week 6 of 8) clinical response (reduction in total Mayo score of ≥3 and ≥30% from baseline with ≥1 point decrease in rectal bleeding subscore [RBS] or absolute RBS ≤1); clinical remission (total Mayo score ≤2 and no subscore >1); endoscopic healing (Mayo endoscopic subscore ≤1); partial Mayo score of 0; patient-reported outcome 2-item remission (RBS of 0 and stool frequency ≤1), resolution of rectal bleeding, and stool frequency normalization. Predictors on univariate analyses with P < .05 were included in multivariate logistic regression models. Placebo-treated patients with normal serum C-reactive protein and albumin levels were more likely to attain clinical response (71 of 437 [16.3%] vs 49 of 660 [7.4%]; adjusted odds ratio, 2.76; 95% confidence interval, 1.19-5.41; P= .018). Compared with patients with a Mayo endoscopic score of 2, patients with a Mayo endoscopic score of 3 were less likely to attain clinical response (105 of 556 [18.8%] vs 179 of 675 [25.9%]; adjusted odds ratio, 0.33; 95% confidence interval, 0.16-0.68; P= .003). Similar findings were observed for clinical remission and resolution of rectal bleeding. Biomarkers such as normal serum C-reactive protein and albumin and baseline endoscopic severity were found to affect placebo response rates in clinical trials of UC. These findings have implications for clinical trial design in UC.

Intestinal Ultrasound Is Accurate to Determine Endoscopic Response and Remission in Patients With Moderate to Severe Ulcerative Colitis: A Longitudinal Prospective Cohort Study

Background & AimsIntestinal ultrasound (IUS) is noninvasive, cost-effective, and accurate to determine disease activity in ulcerative colitis (UC). In this study, we prospectively evaluated IUS for treatment response in a longitudinal cohort by using endoscopy and histology as gold standards. MethodsConsecutive patients with moderate to severe UC (endoscopic Mayo score [EMS] ≥2) starting tofacitinib treatment were included. Patients were evaluated at baseline and after 8 weeks of tofacitinib induction by means of clinical, biochemical, endoscopic (EMS and UC endoscopic index for severity), histologic (Robarts Histopathologic Index) and IUS assessments. Readers of IUS, endoscopy, and histology were blinded for all other outcomes. The primary outcome was difference in bowel wall thickness (BWT) for endoscopic improvement vs no endoscopic improvement. Endoscopic remission was defined as EMS = 0, improvement as EMS ≤1, and response as a decrease of EMS ≥1. ResultsThirty patients were included, with 27 patients completing follow-up. BWT correlated with EMS (ρ = 0.68, P < .0001), UC endoscopic index for severity (ρ = 0.73, P < .0001) and Robarts Histopathologic Index (ρ = 0.49, P = .002) at both time points. BWT in the sigmoid was lower in patients with endoscopic remission (1.4 mm vs 4.0 mm, P = .016), endoscopic improvement (1.8 mm vs 4.5 mm, P < .0001) and decrease in BWT was more pronounced in patients with endoscopic response (−58.1% vs −13.4%, P = .018). The most accurate cutoff values for BWT were 2.8 mm (area under the curve [AUC] 0.87) for endoscopic remission, 3.9 mm (AUC 0.92) for improvement, and decrease of 32% (AUC 0.87) for response. The submucosa was the most responsive wall layer. ConclusionIUS, importantly BWT as the single most important parameter, is highly accurate to detect treatment response when evaluated against endoscopic outcomes.

Time to Endorse A Sensitive Method for Scoring Endoscopic Activity of Ulcerative Colitis in Clinical Research.

The endoscopic scoring of ulcerative colitis is routinely used for both individual patient management and as an endpoint in clinical trials. The most commonly used scoring system is the Mayo endoscopic subscore, which scores endoscopic disease activity on a scale between 0 and 3. With only four possible scores and consideration of only the most involved area of the colon, the Mayo endoscopic subscore lacks sensitivity to change in measuring the totality of the endoscopic inflammatory involvement in patients with ulcerative colitis. Here, we present one case study from clinical practice and one from clinical trials in which using the Mayo endoscopic score leads to potentially incorrect conclusions. Further, in a post-hoc analysis, we re-examined endoscopic videos from a clinical trial and demonstrate that assessing involved ulcerated and affected areas on a segmental level of the colon or summing Mayo scores of colonic segments can identify improvements in endoscopic disease activity in almost twice as many subjects as identified by the Mayo endoscopic subscore alone. Although the alternative scoring systems we have used in this report will need further validation, our findings demonstrate the need for a more sensitive endoscopic scoring system in ulcerative colitis.

External validation of the Paddington International Virtual Electronic ChromoendoScopy ScOre as a good endoscopic score to define mucosal healing and predict long‐term clinical outcomes in ulcerative colitis

To define endoscopic and histological remission in ulcerative colitis (UC) accurately, several scoring systems have been established. A novel virtual electronic chromoendoscopy score, the Paddington International Virtual ChromoendoScopy ScOre (PICaSSO), was developed, validated, and reproduced to assess inflammation grade and predict patient prognosis. We externally verified and validated the clinical value of PICaSSO in UC patients. This prospective study enrolled 63 UC patients. The Mayo endoscopic score (MES), UC Endoscopic Index of Severity (UCEIS), and PICaSSO were adopted for endoscopic evaluation. All biopsy samples were scored using the Robarts histological index (RHI), Nancy histological index (NHI), and "Extent, Chronicity, Activity, Plusadditional findings" (ECAP) score. Patients with an endoscopic MES of 0-1 at baseline were followed up during a median time of 23.5 months. PICaSSO wasstrongly correlated with other endoscopic and histological scoring systems. PICaSSO ≤3 had advantages in assessing histological remission (HR), with the highest accuracy of 88.9% for ECAP-HR. Relapse-free survival rates were significantly different between patients with MES 0 and MES 1 and patients with PICaSSO ≤3 and >3 (P=0.010 and 0.018, respectively). PICaSSO was externally validated with strong correlations with other endoscopic and histological scoring systems in UC, and PICaSSO-ER might potentially predict a better long-term clinical outcome in UC patients.

Impact of Endoscopic and Histologic Activity on Disease Relapse in Ulcerative Colitis.

Endoscopic healing is currently considered the main target in the management of ulcerative colitis (UC). There are conflicting data about the role of histology as a stricter treatment objective. We aim at evaluating the additional benefit of histologic remission over endoscopic remission. We performed a prospective observational study at the McGill University Health Center. We enrolled adult patients with UC in clinical remission for at least 3 months undergoing a colonoscopy. Endoscopic disease activity was based on the Mayo endoscopic score. Rectal biopsies were obtained, and the histologic activity was evaluated using the Geboes score (active disease defined as Geboes score ≥ 3.1) with the addition of assessing the presence of basal plasmacytosis. Patients were followed up for 12 months for disease relapse defined as a partial Mayo score of > 2. At the time of relapse or end of follow-up, all patients underwent repeat endoscopic evaluation. The primary end point was clinical relapse. Two hundred fifty-three patients were included. The presence of basal plasmacytosis was associated with relapse (adjusted odd ratio = 2.07, 95% confidence interval [CI] 1.06-4.18, P = 0.042). Time to clinical relapse was significantly higher for patients with Mayo endoscopic score > 0 with adjusted hazard ratio = 2.65, 95% CI 1.31-5.39, and P = 0.007. Time to clinical relapse was not significantly higher for Geboes score ≥ 3.1 with adjusted hazard ratio = 1.29, 95% CI 0.67-2.49, and P = 0.45. Active histologic disease did not affect time to clinical relapse in patients with UC who achieved endoscopic remission while the presence of basal plasmacytosis is associated with relapse.