Endoscopic Healing Research Articles

The Impact of Endoscopic Healing on Disease-Related Outcomes in Patients With Ulcerative Proctitis.

Ulcerative proctitis (UP) is a limited form of ulcerative colitis. While achieving endoscopic healing (EH) in ulcerative colitis improves long-term outcomes, the benefit of EH in UP is uncertain. This study aimed to assess the impact of EH on outcomes in UP. This single-center retrospective study included adults with UP and ≥2 endoscopies, with active inflammation (Mayo endoscopic score [MES] 1-3) at index. EH was defined as MES 0-1 at follow-up procedure. The relationship of EH to inflammatory bowel disease (IBD)-related outcomes was assessed using univariate analysis and multivariable logistic regression assessed the effect of EH on IBD-related outcomes. Among 200 UP patients, 109 (54.5%) had EH at follow-up endoscopy at median 19 months (interquartile range: 7, 32). EH was associated with fewer IBD-related emergency department (ED) visits (EH: 8.3%, no EH: 21%, P = .01), hospitalizations (5.5% vs 18%), and GI visits (mean: 1.47/year [SD: 1.40], vs 2.96/year [2.52], P < .001). Patients with EH were less likely to have iron deficiency anemia (23% vs 41%, P = .007), Clostridioides difficile (0.9% vs 6.6%, P = .048), or initiate new biologic therapy after relapse (15% vs 33%, P = .034). Patients with EH had a greater time to clinical relapse (21 [24] vs 9 months [14]; P = .006) and lower odds of an IBD-related ED visit (OR: 0.32, 95% CI: 0.13, 0.73) or hospitalization (0.26 [0.09, 0.67]). Baseline presence of a cecal patch did not impact outcomes. UP patients with EH had less IBD-related healthcare utilization, fewer IBD-related complications, and were less likely to escalate therapy after relapse than patients without EH. Using a treatment target of EH may therefore be desirable in UP.

New and current therapeutic goals of chronic inflammatory bowel disease

Chronic inflammatory bowel diseases (IBD), such as Crohn's disease (MC) and ulcerative colitis (CU), are serious immune-mediated diseases that affect the gastrointestinal tract and represent a considerable burden for patients. In recent decades, the treatment of IBD has shifted from symptomatic control to more precise, long-term goals. Advances in IBD research have led to therapy goals having been redefined and expanded in order to achieve complete inflammation control and prevent complications in the long term.An important component of modern therapeutic approaches is the definition of specific markers that serve as indicators for the achievement of these therapeutic goals. These markers enable objective monitoring of the success of treatment and thus offer a clear approach for controlling the therapy. The present article focuses on the new therapeutic goals in IBD treatment and discusses the role of therapeutic target markers in clinical practice.A central goal in modern IBD therapy is endoscopic healing, i.e. the complete macroscopic healing of the intestinal mucosa. In clinical practice this includes in particular an ulcer-free mucosa. In contrast to clinical remission alone, endoscopic healing provides an objective assessment of the inflammatory state and correlates strongly with an improved long-term prognosis.The histologic remission goes beyond endoscopic healing and aims to endoscopic healing to no longer detect signs of inflammation at the microscopic level. This is particularly relevant as the results show that patients who achieve a complete histological remission have an even lower recurrence rate and better long-term results than those who only achieve a clinical or endoscopic remission.Even though no curative therapy for IBD currently exists, the complete cure remains the ultimate goal of research. In current practice, this goal is still unattainable in current practice, but progress in genetic and immunological research offers hope. In the long term, the aim is to innovative approaches such as gene editing or immunotherapy to cure the disease. This could mean that patients are not only free of symptoms, but also freed from the burden of the disease in the long term.

New Interleukin-23 Antagonists' Use in Crohn's Disease.

Crohn's disease (CD) is a chronic inflammatory condition of the digestive tract, driven by an imbalance in immune system regulation, where proinflammatory interleukin-23 (IL-23) plays an essential role. Selective new IL-23 inhibitors, including risankizumab, guselkumab, and mirikizumab, block the IL-23p19 subunit to inhibit the Il-23 action and alleviate inflammation in CD. This review explores the effectiveness, safety, and therapeutic potential of anti-IL-23 treatment in CD management. Risankizumab, guselkumab, and mirikizumab demonstrated considerable effectiveness in inducing clinical remission and promoting endoscopic healing in patients with moderately to severely active CD, including those refractory to anti-TNF therapies. Risankizumab showed favorable results in pivotal trials like ADVANCE, MOTIVATE, and FORTIFY, achieving remission rates of up to 45% and sustained inflammatory biomarkers normalization. Guselkumab and mirikizumab similarly demonstrated substantial efficacy in the induction and maintenance phases, with promising long-term results. The safety profiles of IL-23 inhibitors were favorable, with low rates of serious adverse events, including infections and malignancies. Selective new IL-23 inhibitors represent a targeted and effective therapeutic class for moderately to severely active CD, offering high clinical and endoscopic remission rates, and favorable safety outcomes. Continued research, particularly on long-term efficacy and the selection of patients based on inflammatory biomarkers, will help optimize their role in personalized treatment strategies for refractory CD.

Upadacitinib Results in Endoscopic Remission in Patients With Inflammatory Bowel Disease and Prior Tofacitinib Failure

Goals: Assess the safety and effectiveness of upadacitinib in patients with prior tofacitinib failure. Background: Patients with severe, refractory Crohn’s disease (CD) or ulcerative colitis (UC) and inadequate response to medical therapy have a high risk of complications. A better understanding of treatment response in the setting of prior failure may improve disease control in high-risk patients. Currently, the response to a subsequent Janus Kinase (JAK) inhibitor after prior JAK failure is poorly understood. Study: We retrospectively assessed the safety and effectiveness of upadacitinib in patients with prior tofacitinib failure. Results: We report on 26 patients (10 UC, 16 CD) treated with upadacitinib after tofacitinib failure. Mean age 40.2 years, mean disease duration 14.4 years (range 2 to 33), and previously failed a median of 5 advanced therapies. The mean upadacitinib treatment duration was 13.9 months (SD 4.5). On upadacitinib, 83.3% (n=10/12) of patients achieved clinical response, 66.7% (n=8/12) clinical remission, 71.4% (n=10/14) endoscopic improvement, 57.1% (n=8/14) endoscopic remission, and 35.7% (n=5/14) endoscopic healing. The mean Simple Endoscopic Score in CD decreased from 14.3 (SD: 8.3) to 8.6 (SD: 9.0) (P=0.24). The mean Mayo Endoscopic Subscore significantly decreased from 2.7 (SD 0.8) to 0.9 (SD 1.2) (P=0.006). 73.1% of patients on upadacitinib reported adverse events, most commonly minor infections and acne. No serious adverse events, major cardiovascular events, malignancies, or Shingles were observed. Conclusions: Upadacitinib was tolerated in most patients and resulted in clinical and endoscopic improvement in the majority of patients with severe, refractory CD or UC with prior tofacitinib failure, regardless of previous clinical response to tofacitinib. Further studies would define the long-term safety, efficacy, and predictors of response after previous JAK exposure.

Rates, Predictors, and Outcomes of Ustekinumab Dose Escalation in Inflammatory Bowel Disease.

Ustekinumab (UST) is effective for the induction and maintenance of remission in inflammatory bowel disease (IBD). However, a significant proportion of patients will require UST dose escalation. We sought to determine the rates, predictors, and outcomes of UST dose escalation in patients with IBD. This was a multicenter, retrospective study of all patients with IBD who received UST from January 1, 2014 to March 1, 2022. Primary outcomes were the rates and predictors of UST dose escalation. Secondary outcomes included steroid-free clinical remission, endoscopic healing, and normalization of serum c-reactive protein in patients who underwent UST dose escalation. A total of 198 patients were included (58% females and 76.7% with Crohn's disease). UST dose was escalated by 55.5% (n = 110). Mean baseline albumin was lower in the UST dose escalation group at 3.86 ± 0.47 versus 4.03 ± 0.45g/dL ( P = 0.044). The mean hemoglobin was lower in the UST dose escalation group at 12.1 ± 1.83 versus 12.7 ± 1.42 ( P = 0.049). On multivariate analysis, male sex alone was associated with the need for dose escalation (odds ratio: 4.08, 95% CI: 1.20 - 13.90; P = 0.025). In the UST dose escalation group, 66.1% achieved steroid-free clinical remission, 55.8% had normalization of c-reactive protein, and 35.8% achieved endoscopic healing. UST dose escalation was needed in more than half of patients with IBD in this real-world cohort. UST dose escalation resulted in clinical remission in more than half of the cohort and endoscopic healing in one-third of patients.

Endoscopic healing in IBD: Still the target to achieve?

Mucosal healing is the mainstream goal of modern treat-to-target strategy as it is associated with a significantly more favorable disease course in IBD patients with either ulcerative colitis or Crohn's disease. Recent advances in endoscopic imaging technologies have overcome the traditional concept of mucosal healing assessed with conventional white light imaging, allowing for multiple levels of endoscopic healing up to the boundaries of molecular and functional evaluation. In this review, we focused on conventional and emerging strategies to assess endoscopic healing in ulcerative colitis and ileocolonic Crohn's disease, examining their pros and cons in real life practice.

Vidofludimus Calcium in Patients With Moderate-to-Severe Ulcerative Colitis: A Randomized, Placebo-Controlled, Phase 2 Trial.

Vidofludimus calcium (VidoCa) is a dihydroorotate dehydrogenase inhibitor that demonstrated efficacy in immune-related diseases. This study assessed the safety and efficacy of VidoCa in patients with active ulcerative colitis (UC). This placebo-controlled, phase 2 trial randomized adults with moderate-to-severe UC to receive once-daily VidoCa (10, 30, or 45 mg) or placebo for 10 weeks (induction); patients with symptomatic remission were rerandomized to VidoCa 10, 30 mg, or placebo once daily for an additional 40 weeks (maintenance). The primary endpoint was clinical remission at week 10. Secondary endpoints included symptomatic remission, endoscopic healing, and symptomatic response. The study is registered with ClinicalTrials.gov (NCT03341962) and EudraCT (2017-003703-22). Two hundred sixty-three patients were randomized to induction treatment with VidoCa (10 mg [n = 67], 30 mg [n = 66], and 45 mg [n = 66]) or placebo (n = 64). Sixteen (14%) patients treated with VidoCa (30 mg or 45 mg) achieved the primary endpoint compared with 8 (14%) with placebo. In patients without concomitant corticosteroids, 7 (12%) treated with VidoCa achieved clinical remission at week 10 vs 1 (4%) with placebo. At week 50, dose-dependent increases in the rate of clinical remission ( P = 0.0358), steroid-free clinical remission, and endoscopic healing were observed. Common adverse events (AEs) were headache (4 [6%]), anemia (3 [6%]), vomiting (3 [5%]), and hypertension (3 [5%]) with incidence similar between placebo and VidoCa. Hematuria (4 [6%]) was a treatment-related AE with VidoCa 45 mg only. The incidence of serious AEs was low. VidoCa was safe, well-tolerated, and demonstrated proof-of-concept for dihydroorotate dehydrogenase inhibition to treat UC.

Directionality of endoscopic and histologic healing in ulcerative colitis: a prospective pilot study.

Endoscopic and histologic healing in ulcerative colitis (UC) is hypothesized to progress proximally to distally, with healing of the distal rectosigmoid occurring last. However, this has not been empirically verified. We performed a prospective cohort study in patients with pancolonic UC commencing treatment with a tumor necrosis factor (TNF) antagonist or vedolizumab. Four biopsies were obtained from each of the five colonic segments at colonoscopy, both at baseline and 16-24 weeks after treatment initiation. Independent, blinded central reading of both endoscopic [modified Mayo Endoscopic Subscore (mMES) (score = 1 excludes any friability), UC Endoscopic Index of Severity (UCEIS)] and histologic disease activity [Robarts Histopathology Index (RHI), Nancy Histological Index (NHI), and Geboes Score] was performed for each colonic segment, and changes per segment were calculated. A total of eight patients were recruited (five TNF antagonists, three vedolizumab). There was no significant difference in the mean change between colonic segments for any of the endoscopic disease activity indices (P value based on Kruskal-Wallis test for differences between ascending, transverse, descending, sigmoid colon, and rectum: 0.328 for mMES and 0.317 for UCEIS). Similarly, there was no difference in change in histologic activity between colonic segments (P = 0.357 for RHI, P = 0.410 for NHI, P = 0.734 for Geboes score). We did not observe evidence of an anatomical healing gradient in UC across different colonic segments, nor evidence of delayed distal improvement. Larger studies are required to validate whether the rectum truly does heal last in UC.

AN EVALUATION OF ENDOSCOPIC HEALING IN PEDIATRIC CROHN’S DISEASE USING MULTIPLE ENDOSCOPIC SCORING METHODS IDENTIFIES SIMILARITIES IN BLOOD AND STOOL BIOMARKERS

Abstract BACKGROUND Pediatric Crohn’s Disease (CD) patients who achieve deep remission, defined as both clinical remission and endoscopic healing (EH), have fewer disease complications. The gold standard for assessing EH is ileocolonoscopy (IC), which can be invasive and costly. EH can be calculated using multiple scoring systems including the common Simple Endoscopic Score for Crohn’s Disease (SES-CD), the Simplified Endoscopic Mucosal Assessment for Crohn’s Disease (SEMA-CD) which streamlines scoring, or the Modified Multiplier SES-CD (MM-SES-CD), which uses weights for each SES-CD parameter based on prognostic value. Here, we sought to identify biomarkers associated with EH. As a secondary endpoint, we sought to validate the SEMA-CD and MM-SES-CD in our population and use these scoring methods to further evaluate biomarkers. METHODS A multicenter, cross-sectional study enrolled CD patients scheduled for an IC. Inclusion was age 2-21 years receiving either infliximab (IFX) or adalimumab (ADA) for &amp;gt;6 months. Blood samples were collected to measure c-reactive protein (CRP), serum albumin (ALB), neutrophil CD64 activity ratio (nCD64), soluble CD64 (sCD64), and drug concentrations. Fecal calprotectin (fCal) and fecal lactoferrin (fLacto) were measured from stool prior to the IC. The SES-CD and SEMA-CD were calculated from video recordings by two separate reviewers, when possible. MM-SES-CD was tabulated from the SES-CD scores. Agreement between endoscopic scores was calculated using intraclass correlation coefficient (ICC). Pair-wise comparisons were made using parametric or non-parametric tests as appropriate. RESULTS Of the 91 enrolled patients, 87 had a complete IC. EH defined by SES-CD&amp;lt; 3, SEMA-CD&amp;lt; 1 and MM-SEC-CD&amp;lt; 14 was achieved in 55.1%, 45.3%, and 67.8% of patients, respectively. The ICC for the SES-CD was 0.91 (95% CI: 0.84-0.95), 0.87 (0.77-0.93) for SEMA-CD, and MM-SES-CD 0.87 (0.77-0.93). There was excellent correlation between the SES-CD and SEMA-CD (Spearman r=0.89, p&amp;lt; 0.001) and MM-SES-CD (Spearman r=0.99, p&amp;lt; 0.001) and between the SEMA-CD and MM-SES-CD (Spearman r=0.89, p&amp;lt; 0.001). We found that lower levels of fCal, fLacto, CRP, novel biomarkers sCD64 and nCD64, and an elevated ALB level were significantly associated with EH for all scoring modalities. Patients without EH had more rapid IFX clearance using SES-CD only. Cut points (Youden Index) were identified for each biomarker and demonstrated notable similarity across scoring methods (Table1). CONCLUSIONS We identified remarkable similarities in EH blood and stool biomarkers using different endoscopic scoring modalities, highlighting the reliability of these markers to detect inflammation. However, our results also indicate that some important EH markers, like drug clearance, may be missed using a singular endoscopic scoring system. Table 1. Biomarkers of Endoscopic Healing by Endoscopic Scoring System

Effectiveness of biologics for endoscopic healing in patients with isolated proximal small bowel Crohn's disease.

Endoscopic healing (EH) is a key therapeutic target in Crohn's disease (CD). Proximal small bowel (SB) lesions in patients with CD are associated with a significant risk of strictures and bowel resection. Assessing SB in patients with CD is necessary because of its significant therapeutic implications. The advent of biologic therapies, including infliximab, ustekinumab, and vedolizumab, has significantly altered CD treatment. However, data on the efficacy of biologics in achieving EH, specifically in the proximal SB of patients with CD, remain limited. To assess the effectiveness of biologics for EH in patients with jejunal and/or proximal ileal CD. Between 2017 and 2023, we retrospectively included 110 consecutive patients with isolated proximal SB CD, identified through baseline balloon-assisted enteroscopy. These patients completed 1-year of treatment with infliximab, ustekinumab, or vedolizumab, and underwent a second balloon-assisted enteroscopy at 1 year. Complete EH was defined as a modified Simple Endoscopic Score for CD (SES-CD) of < 3, while EH of the jejunum and proximal ileum was defined as a segmental modified SES-CD of 0. In total, 64 patients were treated with infliximab, 28 with ustekinumab, and 18 with vedolizumab. The complete EH rate at 1 year was 20.9% (23/110), with 29.6% (19/64) for infliximab, 10.7% (3/28) for ustekinumab, and 5.5% (1/18) for vedolizumab. The median modified SES-CD significantly decreased compared to baseline [5 (2-8) vs 8 (6-9), P < 0.001]. The jejunal and proximal ileal EH rates at 1 year were 30.8% (12/39) and 15.5% (16/103), respectively. Multiple logistic regression analysis showed that stricturing or penetrating disease [odds ratio (OR) = 0.261, 95%CI: 0.087-0.778, P = 0.016], prior exposure to biologics (OR = 0.080, 95%CI: 0.010-0.674, P = 0.020), and moderate-to-severe endoscopic disease (OR = 0.277, 95%CI: 0.093-0.829, P = 0.022) were associated with a lower likelihood of achieving EH at 1 year. Only 20.9% of patients with isolated proximal SB CD achieved complete EH after 1 year of biologic therapy.

A64 VALIDATION OF THE MODIFIED MULTIPLIER OF SES-CD (MM-SES-CD) TO PREDICT ENDOSCOPIC REMISSION IN CROHN’S DISEASE: A POST HOC ANALYSIS OF THE SEAVUE TRIAL

Abstract Background The modified multiplier of the SES-CD (MM-SES-CD) has been shown to have prognostic value for predicting endoscopic healing (EH) in patients with Crohn’s disease. Aims The purpose of this analysis was to validate baseline categories of endoscopic disease severity using the MM-SES-CD and determine their prognostic value for predicting one-year EH. Methods Participants in the SEAVUE trial (n = 386) were categorized based on baseline endoscopic disease severity using MM-SES-CD cut-offs into mild (≥22.5 to &amp;lt; 31), moderate (≥ 31 to &amp;lt; 45) and severe (≥45) disease. The primary outcome was achievement of endoscopic healing (EH) based on MM-SES-CD score (&amp;lt; 22.5) at one year. Secondary outcomes included achieving clinical remission based on patient-reported outcomes and normalization of fecal calprotectin in patients with raised baseline levels at one year. Results MM-SES-CD &amp;lt; 22.5 at one year was achieved in 62.0% of patients with baseline mild endoscopic disease, 48.6% with moderate disease and 33.8% with severe disease (p &amp;lt;0.001). Similarly, a trend was observed for patient-reported outcome (PRO-2) clinical remission, which was achieved in 78.9% of patients with baseline mild endoscopic disease, 72.9% of those with moderate and 66.2% of those with severe disease (p=0.09). Likelihood of fecal calprotectin (FCP) normalization was significantly associated with baseline endoscopic disease severity (p=0.008). Conclusions Baseline MM-SES-CD-based cutoffs for endoscopic disease severity demonstrate prognostic value for achieving one-year EH, PRO2 remission, and FCP normalization. These findings suggest that the MM-SES-CD can be used both to measure baseline endoscopic disease severity and predicts post-maintenance outcomes in patients with CD. Figure 1: Percentage of patients in MM-SES-CD remission (&amp;lt;22.5) at week 52 stratified by baseline MM-SES-CD categories (Mild ≥ 22.5 to &amp;lt; 31, moderate ≥ 31 to &amp;lt; 45, severe ≥ 45) Funding Agencies:

Ustekinumab Drug Clearance Is Better Associated with Disease Control than Serum Trough Concentrations in a Prospective Cohort of Inflammatory Bowel Disease.

Background/Objectives: This study aimed to compare the association of ustekinumab (UST) drug clearance (CL) and trough drug concentrations with disease activity in patients with inflammatory bowel diseases (IBDs). Methods: A prospective cohort of 83 patients with IBD receiving maintenance therapy with 90 mg subcutaneous UST was analyzed using Bayesian PK modeling. UST concentrations and antibodies to UST (ATU) were collected at the trough and measured using a drug-tolerant homogenous mobility shift assay (HMSA). CL was estimated using Bayesian estimation methods with priors from a previous population pharmacokinetic study specifically reparametrized using HMSA. Outcomes were combined clinical and biochemical remission and endoscopic healing index (EHI) score, a validated marker of endoscopic active disease in IBD. Statistical analysis consisted of linear and nonlinear mixed effect models for repeated time-to-event analysis. Results: A total of 83 patients with IBD were enrolled (median age 42 years, 52% female) and evaluated across 312 dose cycles (median follow-up: 279 days, median of 3 cycles/patient). Median concentrations and CL were 5.0 µg/mL and 0.157 L/day, respectively. Most patients (89%) were exposed to other biologics before starting UST, which was associated with lower rates of clinical and biochemical remission (p = 0.01). Longitudinal changes in concentrations were not associated with remission (p = 0.53). Conversely, higher CL was associated with a lower likelihood of remission (p < 0.01). EHI > 50 points (endoscopic active disease, n = 303 cycles) was associated with higher UST CL (p < 0.01). Conclusions: UST CL was more strongly associated with clinical and biochemical outcomes than trough concentrations, highlighting its potential role in therapy optimization.

Comparison of 1-Year Clinical Course in Patients With Newly Diagnosed Inflammatory Bowel Disease Between Vietnam and Korea: A Multinational, Multicenter Retrospective Cohort Study.

The differences in the clinical course of Crohn's disease (CD) and ulcerative colitis (UC) among Asian countries remain unknown. Thus, we compared the clinical characteristics, treatment, and one-year outcomes of newly diagnosed inflammatory bowel disease (IBD) patients between Vietnam and Korea. A retrospective cohort study was conducted at seven tertiary hospitals in these countries between January 2020 and January 2021. Data on demographics, diseases, treatment, and outcomes during 1 year after diagnosis were collected. Among 225 patients (60 from Vietnam and 165 from Korea), 140 and 85 were diagnosed with UC and CD, respectively. Severe activity (p < 0.01) and extensive colitis (p < 0.01) in UC, along with complicated behavior in CD (p < 0.01), were more frequently observed in Vietnamese patients compared to Korean patients. The proportion of UC patients using corticosteroids (p < 0.01), immunomodulators (p < 0.01), and biologics (p = 0.026) was significantly higher in Vietnam. In contrast, the proportion of UC patients using topical mesalamine (p < 0.01) was significantly higher in Korea. The intervals from CD diagnosis to biologic therapy initiation (p = 0.04), as well as from UC diagnosis to corticosteroid (p < 0.01), immunomodulator (p < 0.01), and biologic therapy (p < 0.01) commencement, were significantly shorter in Vietnamese patients compared to Korean patients. However, the proportions of endoscopic healing and complications at 1-year follow-up did not significantly differ between the countries (p > 0.05). Although Vietnamese IBD patients had higher baseline clinical and phenotypic severity than their Korean counterparts, no significant differences in short-term outcomes were observed, potentially reflecting the impact of the higher rate and early biologic usage in Vietnamese patients.

Utility of Serum-Based Markers to Predict Severity, Histological Activity, and Rehospitalisation in Ulcerative Colitis

Introduction: Inflammatory Bowel Disease (IBD) comprises ulcerative colitis (UC) and Crohn’s disease (CD). Serum-based non-invasive biomarkers are suggested for endoscopic and histological healing in clinical practice. Aims: The aim of this study was to investigate the utility of serum-based markers to predict severity, histological activity, and rehospitalization in ulcerative colitis. Materials and Methods: This was a cross-sectional study that was performed in a tertiary care center from October 2022 to March 2023. Diagnosis of ulcerative colitis on the basis of clinical history, imaging findings, flexible sigmoidoscopy/colonoscopy findings, and histopathology reports and agreed to participate were included. All the data, including blood parameters, were analysed. Results: C Reactive Protein (CRP)/albumin (AUC 0.821; 95% CI: 0.732 to 0.891, cut off point of &gt;2.57), (AUC 0.875; 95% CI: 0.794 to 0.933, cut off point of &gt;4.13) was the best predictor for correctly predicting endoscopic severity (UCEIS) and active histological inflammation and also a good predictor of re-hospitalization in the last 6 months (AUC 0.814; 95% CI: 0.724 to 0.885, cut off point of &gt;6.34) as compared to red cell distribution width (RDW)/albumin (AUC 0.598; 95% CI: 0.495 to 0.695), (AUC 0.537; 95% CI: 0.434 to 0.637), which was non-significant. RDW/Albumin (AUC 0.793; 95% CI: 0.701 to 0.868) also predicts 6-month rehospitalization significantly but less as compared to CRP/Albumin. Conclusion: In ulcerative colitis, the CRP/ALB ratio was a strong predictor of endoscopic severity, histologic disease activity, and rehospitalization in 6 months. It can be used to predict treatment response and as an indirect biomarker for mucosal healing.

P0439 Ultrasound transmural healing reduces the risk of relapse in Crohn’s disease patients with endoscopic mucosal healing: results of a prospective study

Abstract Background The STRIDE II guidelines recognize endoscopic healing as one of the main therapeutic targets in Crohn’s disease (CD). Nevertheless, transmural healing could reduce the risk of long-term complications. The aim of this study was to assess the risk of long-term complications in CD according to the degree of endoscopic and ultrasound healing. Methods We conducted a prospective study that included all patients with CD in clinical remission who underwent colonoscopy with endoscopic healing (CDEIS &amp;lt;4) and intestinal ultrasound (IUS) within 4 weeks between September 2019 and September 2022. IUS transmural healing was defined by a parietal thickness &amp;lt; 3 mm on all digestive segments (colonic and ileal) without colour doppler signal. The primary endpoint was CD relapse, defined as the need for drug intensification, initiation of corticosteroid therapy, CD-related hospitalization, development of a perianal and luminal fistula or abscess, or the need CD-related bowel surgery. Patients were followed up at least every 6 months for two years. Results A total of 93 patients were included, the majority of whom were women (53%) with ileocolic location (43%). The median disease duration was 12 years (IQR, 4-19) and 71% patients were treated with anti-TNF. Ultrasound transmural healing was observed in 73% (68/93) of patients. After a median follow-up of 22.5 months [IQR, 19.3-23.7], relapse was significantly higher among patients without IUS transmural healing (48% vs. 18% p = 0.007). Relapse rate at 6 and 12 months were significantly higher among patients without IUS transmural healing (22% vs. 9% and 22% vs. 13%; p = 0.019). In multivariate analysis, the risk of relapse was 5 times higher without IUS transmural healing (HR 5.5 (2.1-14.2) p &amp;lt; 0.001). Conclusion IUS transmural healing was associated with a lower risk of relapse among patients with endoscopic healing and could be considered as a non-invasive therapeutic target in CD.

P0559 Endoscopic healing at 1-year and association with long-term quality of life in ulcerative colitis: A pooled clinical trial analysis adjusting for 1-year clinical remission status

Abstract Background Therapeutic goals and clinical guidelines in inflammatory bowel disease have evolved to include endoscopic outcomes being a key prognostic parameter in disease management. STRIDE-II guidelines are comprised of clinical and patient-reported outcome remission, along with biomarker normalization and endoscopic healing. While available publications have correlated achievement of endoscopic outcomes with long-term outcomes, few if any have adjusted for clinical remission status. The objective of this analysis was to assess the impact of endoscopic healing at the end of 1-year and 2-year quality of life while adjusting for clinical remission status at 1-year using clinical trial data. Methods Data from four randomized ulcerative colitis clinical trials (UNIFI:NCT02407236, PURSUIT:NCT01863771, ACT-1:NCT00036439, ACT-2:NCT00096655) were pooled to assess the impact of endoscopic healing at 1 year on patients’ quality of life as assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ). This post-hoc analysis assessed endoscopic healing at the end of maintenance (EOM) (~42 weeks) and IBDQ remission in the long-term (LTE) duration (~126 weeks). Endoscopic healing was based on endoscopy sub-score of the Mayo score = 0 or 1 and IBDQ remission was defined as IBDQ total score&amp;gt;=170. Patients without LTE IBDQ data and placebo treated patients were excluded. Multivariate analyses with trial as a random effect were conducted and adjusted for treatment arm during maintenance, clinical remission status at end of maintenance (EOM), and endoscopic healing at EOM. Results A total of 591 patients had available endoscopy and clinical remission status at EOM. The percentage of patients with endoscopic healing reaching LTE IBDQ remission was 80.7% whereas 56.2% of those without endoscopic healing reached IBDQ remission. Results of the multivariate analyses showed that endoscopic healing at EOM was significantly associated with higher odds of LTE IBDQ remission with an OR of 1.78 and a corresponding p value below 0.05. Conclusion This analysis used clinical data from robust trials and adjusted for patients’ clinical remission status at the end of maintenance to isolate the benefit of endoscopic healing in predicting long-term outcomes in UC. Endoscopic healing is significantly associated with a higher likelihood of experiencing a better quality of life.

P0502 Impact of Endoscopic and Histologic Activity on Disease Relapse in Ulcerative Colitis: 3-year and 5-year follow-up

Abstract Background Endoscopic healing in patients with ulcerative colitis predicted higher rates of clinical remission at 12 months follow-up. Meanwhile, active histologic disease did not affect time to clinical relapse in patients with UC who achieved endoscopic remission while the presence of basal plasmacytosis was associated with relapse. [1] We aim to evaluate the impact of baseline endoscopic and histological healing on long-term clinical relapse as well as the rates of UC-related emergency room (ER) visits, hospitalizations and surgery. Methods This prospective observational study was conducted at the Inflammatory Bowel Disease (IBD) Centre of McGill University Health Centre (MUHC) July 2012 to July 2020 and included all adult UC patients undergoing a colonoscopy with biopsies for disease assessments. Patient must have been in clinical remission with a stable dose of medication for at least 3 months prior to enrolment. Patients were followed every 3 months in the first year then every 6-12 months to assess disease relapse, defined as a partial Mayo score (PMS) &amp;gt;2. Active endoscopic disease was defined as Mayo endoscopic score (MES) of 2 or 3. Active histological disease was defined as a Geboes score ≥3.1 (epithelial neutrophils with or without crypt destruction/erosions). Results A total of 253 patients were included in this study. At the 3-year follow-up, baseline active endoscopic and histological disease did not predict clinical relapse. However, baseline endoscopy with a EMS of 0 (compared to 1-3) showed a trend towards significance in predicting relapse (P = 0.08). Multivariate analysis adjusting for age, gender, height, and smoking status remained non-significant (P = 0.0837, 95% CI 0.29–1.08). At 5 years, baseline histological activity did not predict risk of clinical relapse, however, endoscopy with EMS 0 significantly predicted clinical relapse (P = 0.0080), with multivariate analysis confirming this (P = 0.0110, 95% CI 0.27–0.84). Baseline endoscopy with EMS 1-3 was linked to increased ER visits at 3 years (P = 0.02), but not at 5 years (P = 0.7618). Histological disease activity was not linked to increased ER visits at 3 and 5 years. Neither baseline endoscopy nor histology predicted the risk of hospitalisation or surgery at either follow-up (P &amp;gt; 0.05). Conclusion Active histologic disease did not predict long-term clinical relapse at 3- or 5-years point. On the other hand, baseline endoscopic activity of EMS of 0 compared to 1-3, only predicted clinical relapse at 5 years and IBD-related ER visits at 3 years. This long-term follow up data questions the additional role of histology in patient with complete endoscopic healing.

P0370 Transmural healing in Ulcerative Colitis patients improves long-term outcomes compared to endoscopic healing alone

Abstract Background Endoscopic healing (EH) is recognised as a long-term treatment goal for patients with ulcerative colitis (UC).1 We investigated whether transmural healing (TH) in UC as assessed by intestinal ultrasound (IUS) is associated with improved outcomes compared to EH alone. Methods We performed a retrospective study on patients with left-sided or extensive UC on stable maintenance treatment who had EH (Mayo Endoscopic Sub score [MES] ≤1) and an intestinal ultrasound (IUS) performed within six months of an endoscopy with no treatment alterations between IUS and endoscopy. Patients with ulcerative proctitis or on corticosteroids were excluded. TH was defined as bowel wall thickness (BWT) &amp;lt; 3mm. The primary outcome was relapse-free survival in patients with and without TH. UC relapse was defined as at least two of the following: Simple Clinical Colitis Activity Index of ≥ 5 or physician’s global assessment of relapse; fecal calprotectin ≥ 250 ug/g; MES of ≥ 2 on any bowel segment; BWT of ≥ 3mm on any bowel segment (excluding the rectum). Results A total of 61 patients with a median follow up of 20 months were included (Table 1). The relapse risk for the first and second year was 7.5% and 20.5% for the TH group, respectively, compared to 29.4% and 64.3% for the non-TH group (p=0.004, Figure 1). The mean time to the first relapse, was 20.9 ± 11.1 months for the TH group and 12.2 ± 7.8 months for the non-TH group (p=0.042). The risk of relapse for MES 0 at the first year was lower than MES 1 (3.7% compared to 20.8%), although this was not statistically significant (p=0.059). When stratifying for MES 1, TH showed improved relapse free survival for patients with MES 1 compare to those without TH (p=0.045, Figure 1). Moreover, there was a trend towards shorter time to relapse for patients with MES 1 without TH compared to those with TH (12.2 ± 7.8 months vs 18.4 ± 7.6 months) In multivariate Cox regression, female gender (hazard ratio [HR], 2.63; 95% CI, 1.05-6.58; p=0.039), ≥ 2 previous advance therapies (HR, 4.06; 95% CI 1.08-15.28; p=0.038) and non-TH (HR, 3.99; 95% CI 1.31-12.20; p=0.015) were associated with a relapse whereas EH level (MES 0 vs MES 1) was not an associated factor (HR, 1.06; 95% CI 0.32-3.55; p=0.924). Conclusion In UC patients, transmural healing is associated with lower relapse risk compared to endoscopic healing alone. These findings implicate that intestinal ultrasound is a non-invasive, low-cost alternative to endoscopy for stratifying UC patients for risk of relapse.

P0805 Sigmoidoscopy is sufficient as a surveillance tool in pediatric Ulcerative Colitis; full colonoscopy is not typically needed

Abstract Background Sigmoidoscopy is a less invasive procedure than full colonoscopy, demands simpler preparation, requires shorter procedure time, and may be conducted with lighter sedation. Despite these advantages and the continuous nature of inflammation in ulcerative colitis (UC), which typically decreases from distal to proximal colon, the FDA recently requests full colonoscopy to assess UC in clinical trials (i.e. 3 colonoscopies in 54 weeks). Data to support this requirement are scarce in children. We, thus, aimed to assess the necessity of full colonoscopy versus limited sigmoidoscopy in pediatric UC. Methods We included two prospectively enrolled cohorts of children (0-18 years) with UC, both with identical data collection relevant to this study: one from a single-center prospective registry, and the other from a prospective validation of the TUMMY-UC, a patient-reported signs and symptoms for pediatric UC. In addition to explicit clinical, disease activity, labs and demographic data, the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) was recorded prospectively for each colonic segment. The first colonoscopy available after the time of diagnosis was included to better mirror the scenario of post-treatment follow-up monitoring, since the diagnostic procedure should always be full colonoscopy. Results A total of 85 patients were included (mean age 14 ± 3.4, 11 [13%] with endoscopic healing, 45 [53%] with mild colitis and 29 [34%] with moderate-severe colitis). The median UCEIS scores decreased progressively from the rectum and sigmoid (2, IQR:0-4) to the more proximal colon (descending 1, IQR:0-3; transverse and ascending 0, IQR:0-2; p &amp;lt; 0.001). Only 3 patients (3.5%) had inflammation in proximal segments without having inflammation in the rectosigmoid region. Another 10 patients (12%) had higher inflammation scores in the proximal colon than in the rectosigmoid (i.e. reverse gradient), though inflammation was still present in the rectosigmoid region. Conclusion In 96.5% of cases, endoscopic healing in the rectosigmoid region reflected endoscopic healing in the entire colon in children with UC. When inflammation was present in the rectosigmoid, in 86% the degree of colitis reflected the maximal endoscopic severity of the entire colon. These findings suggest that sigmoidoscopy may be a suitable routine post-treatment surveillance tool for pediatric UC patients and in the research setting in order to maximize feasibility and ethical considerations of clinical trials.

P0421 Clinical validity of a seroproteomic index of endoscopic activity in pediatric Crohn’s disease

Abstract Background A seroproteomic index (i.e. the serum index) corresponds to 13 protein markers, including CRP, combined as a multianalyte assay with a score range 0-100 where higher score is associated with higher probability of endoscopic activity in adult CD. We aimed to evaluate its performances in pediatric CD. Methods Children with CD were enrolled from two separate cohorts. Cohort 1 enrolled CD from multiple centers in the United States (n=118) and cohort 2, was multinational (n=160). A simple endoscopic score for CD (SESCD) was collected (&amp;lt;3 points indicate endoscopic healing) with a blood specimen. Clinical disease status was measured using the Harvey Bradshaw index (HBI, cohort 1) or pediatric CD activity index (PCDAI, cohort 2) (PCDAI&amp;lt;10 or HBI&amp;lt;5 indicate clinical remission). Fecal calprotectin (FC) was collected in 180 patients from both cohorts. Serum specimens were processed in Prometheus Laboratories, San Diego, CA. Statistical analysis consisted of linear regression analysis, calculation of receiver operating characteristics curves (ROC) with area under the curve (AUC), sensitivity, specificity, Odds ratio (OR). Results In the 278 enrolled children (median age 14 years [IQR: 12-16 years], 46% females), median SESCD was 5 points (IQR: 0-12 points, 63% with endoscopic active disease); median CRP was 2.5 mg/L (IQR: 0.3-8.4 mg/L), median FC was 592 µg/g (IQR: 135-1147 µg/g) and median serum index was 33 (IQR: 17-60 points). AUROC analysis yielded significantly better area under ROC curve (AUROC, 0.87±0.03) for FC than the serum index (0.78±0.04) and CRP (0.77±0.04) (p&amp;lt;0.05) in distinguishing endoscopic active disease from endoscopic healing. There was a 9-fold higher likelihood of endoscopic active disease with serum index above 32 points (OR= 8.95 [95%CI: 5.02,15.96] p&amp;lt;0.001) with 70% sensitivity and 79% specificity (PPV=85%; NPV=61% at 63% pretest) (Table). In multivariate analysis EHI above 32 points (aOR= 3.00 [95%CI: 1.25, 4.76] p=0.043), active clinical disease (aOR= 2.01 [95%CI: 0.85, 4.76] p=0.114), FC&amp;gt;250 µg/g (aOR= 5.61 [95%CI: 2.4,13.09] p&amp;lt;0.01) and CRP above 3 mg/L (aOR=2.09 [95%CI: 0.9-4.85])(p=0.08) associated with active endoscopic disease) (Figure). In the subset with clinical remission (n=158), or CRP below 3 mg/L (n=136), or FC levels below 250 µg/g (n=116), EHI above 32 points was still associated with higher likelihood of endoscopic disease (OR=5.4 [95%CI: 2.6,11.1], OR= 6.8 [95%CI: 2.9,15.8], and OR=4.0 [95%CI: 1.3,12.8], respectively) (p&amp;lt;0.05) (Figure). Conclusion These data support the association of the serum index with endoscopic outcome in pediatric CD patients.