Mayo Endoscopic Subscore Research Articles

ADEQUACY OF SIGMOIDOSCOPY IN COMPARISION TO COLONOSCOPY TO ASSESS DISEASE ACTIVITY DURING FOLLOW UP IN PATIENTS WITH ULCERATIVE COLITIS

Abstract BACKGROUND Endoscopic remission is the current treatment target in patients with Ulcerative Colitis (UC). Literature on adequacy of sigmoidoscopy in comparison to colonoscopy to assess endoscopic and histologic activity during follow up is sparse. METHODS This is an interim analysis of a prospective study of patients diagnosed with UC with disease extent proximal to the sigmoid colon. Fifty adult patients underwent a complete colonoscopy with segmental biopsies. Endoscopic disease activity was graded using Mayo Endoscopic Subscore (MES) and the Ulcerative Colitis Endoscopic Index of Severity score (UCEIS). The histological grading was done using the Nancy score, Robarts Histopathology Index (RHI) and Simplified Geboes Score (SGS). The maximum rectosigmoid disease activity was compared with the maximum disease activity in the rest of the colon. RESULTS Endoscopic Correlation: Sigmoidoscopic evaluation using MES showed good correlation with pan colonoscopic evaluation for disease activity with a sensitivity of 92.11%, specificity of 66.67%, accuracy of 86% (95% CI – 73.26% to 94.18%), kappa value (k) of 0.58 (p value < 0.001) and Area under curve (AUC) of 0.82 (95% CI- 0.74 to 0.942). Similarly, sigmoidoscopic evaluation using UCEIS score showed good correlation with pan colonoscopic evaluation for disease activity with a sensitivity of 95.0%, specificity of 70%, accuracy of 90% (95% CI – 78.19% to 96.67%), k of 0.68 (p value < 0.001) and AUC of 0.895 (95% CI- 0.805 to 0.924). Disease activity in the colon missed by performing a sigmoidoscopy using MES and UCEIS score is only 6% and 4% respectively. Histological Correlation: Histologic findings in rectosigmoid showed good correlation with histologic findings in rest of the colon using Nancy’s score [Sensitivity of 97.96%, specificity of 100%, accuracy of 98% (95% CI – 89.35% to 99.95%), k of 0.658 (p value < 0.001) and AUC of 0.99 (95% CI- 0.959 to 1.0)], Simplified Geboes Score [Sensitivity of 97.92%, specificity of 100%, accuracy of 98% (95% CI – 89.35% to 99.95%), k of 0.79 (p value < 0.001) and AUC of 0.99 (95% CI- 0.962 to 1.0)], and Robarts Histopathology Index [Sensitivity of 95.56%, specificity of 80%, accuracy of 94% (95% CI – 83.45% to 98.75%), k of 0.694 (p value < 0.001) and AUC of 0.878 (95% CI- 0.667 to 1.0) ]. Histologic disease activity in the colon missed by performing a sigmoidoscopy using Nancy score, SGS and RHI is only 2%, 2% and 4% respectively. CONCLUSION In patients diagnosed with UC and having disease extent proximal to the sigmoid colon, sigmoidoscopic evaluation has good correlation with pan colonoscopic evaluation for grading endoscopic and histological disease activity. A sigmoidoscopic examination is adequate to assess the disease activity in patients with disease extent proximal to the sigmoid colon.

INFLAMMATORY BOWEL DISEASE RISK STRATIFICATION AND MANAGEMENT IN A COMMUNITY PRACTICE SETTING

Abstract INTRODUCTION Risk stratification of patients with Inflammatory Bowel Disease (IBD) is integral for patient management according to care pathways and IBD guidelines. We examined explicit IBD risk stratification and the extent of its influence on patient management in a community-based practice setting. MATERIAL AND METHODS This was a single-center, retrospective study of adult patients with IBD followed at Genesis Healthcare Partners between January 1, 2016 and December 31, 2018. 250 consecutive IBD charts were reviewed for (a) patient demographics; (b) disease characteristics; (c) explicit risk stratification and disease activity documented by clinician provider; (d) management and treatment. Patients were independently risk stratified based on AGA clinical care pathway risk factors (implicit risk stratification). CD high risk factors include: age under 30 at diagnosis, extensive anatomic involvement, perianal and/or severe rectal disease, deep ulcers on endoscopy, stricturing and/or penetrating behavior, prior surgical resection. UC high risk factors include age under 40 at diagnosis, extensive anatomic involvement, deep ulcers on endoscopy, high CRP and/or ESR, steroid requiring disease, C Difficile or CMV infection, prior hospitalization for UC. RESULTS 211 eligible patients: 77 (36.5%) with Crohn’s Disease (CD) and 134 (63.5%) with Ulcerative Colitis (UC) were included; 52% female, 85% Caucasian, median age at diagnosis was 33 years, median length of CD was 16 years, and the median length of UC was 8 years. 18 (2%) had explicit risk stratification documented. Implicit risk stratification was: CD: 9 (12%) low risk [zero high risk factors], 68 (88%) high risk [one or more high risk factors]. UC: 27 patients (20%) low risk [zero high risk factors]; 107 patients (80%) high risk [one or more high risk factor]. Medication management for low-risk CD: 5-ASAs: 5 (56%); locally acting steroids: 5 (56%); systemic steroids: 1 (11%); immunomodulators (IMM): 2 (22%); and biologics: 4 (44%) and high-risk CD: 5-ASAs: 17 (25%); locally acting steroids 18 (27%); systemic steroids 20 (30%); IMM: 21 (31%); biologics: 46 (69%). Medication management for low-risk UC: 5-ASAs: 24 (92%); locally acting steroids: 5 (19%); systemic steroids: 4 (15%); IMM: 2 (8%); biologics: and 1 (4%) and high-risk: 5-ASAs: 97 (91%); locally acting steroids: 42 (39%); systemic steroids: 45 (42%); IMM: 16 (15%); biologics: 44 (41%). Of 182 UC endoscopy procedures explicit Mayo endoscopic sub-scores was documented in 3 (2%). Implicit Mayo Scoring was: 21% Mayo 0, 34% Mayo 1, 26% Mayo 2 and 16% Mayo 3. CONCLUSIONS Explicit risk stratification and Mayo endoscopy scoring was infrequently documented. Embedding risk stratification tools and standardized Mayo endoscopy scoring into EMRs would help to standardize documentation.

P239 Ulcerative Colitis Index of Severity is a better predictor of histologic activity than Mayo endoscopic subscore, an Asian cohort study in ulcerative colitis

Abstract Background Targets of therapy in ulcerative colitis (UC) have undergone a shift from clinical remission to endoscopic healing (EH). Recent STRIDE II guidelines1 have recommended stricter criteria for EH, Ulcerative Colitis Index of Severity (UCEIS) ≤1 or Mayo endoscopic subscore (MES)=0, with histologic healing (HH) as an adjunctive endpoint. We aim to ascertain the strength of correlations between EH and HH using validated indices in an Asian cohort. Methods A single-centre cohort study was performed in a tertiary centre. Patients with a diagnosis of UC were prospectively enrolled into a database from January 2017 to June 2020. Patient demographics, clinical classification, endoscopic and histological assessments were collected retrospectively and analysed. Endoscopic scores in the worst affected segments by two independent gastroenterologists. Histological activity was assessment by a single gastrointestinal histopathologist using the Nancy Histological Index (NHI). Analysis was done using SPSS v23. Spearman correlations between UCEIS, MES and NHI was performed. Results A total of 88 patients with UC were enrolled (Figure 1). Seven patients were excluded as no biopsies were done during endoscopy. Analysis was done for 163 pairs of endoscopy and histology. The distribution of UCEIS, MES and NHI scores for all endoscopies are shown in Figure 2. Both MES and UCEIS had modest correlations with NHI but UCEIS had a stronger correlation to NHI (r=0.640, p<0.01) than MES (r=0.538, p<0.01) (Figure 3). When evaluating patients in EH (UCEIS≤1 or MES=0), both endoscopic scores had similar distribution of NHI scores (Figure 4a & 4b). Despite appearing to be endoscopically inactive, more than half of patients had histologically active disease, with NHI≥2 (14/27 [51.8%] in the UCEIS≤1 group, 9/17 [52.9%] in the MES=0 group). When using the older definition of EH (MES≤1), 49 of 66 patients (74%) had histologically active disease with NHI≥2 (Figure 4c). Conclusion UCEIS ≤1 is slightly more predictive of HH than MES=0 but endoscopic correlation with HH is poor. Biopsies should still be performed if HH is a desired treatment outcome. The more stringent criteria change for EH in STRIDE II from MES≤1 to MES=0 results in higher rates of HH. Reference 1. Turner D, et al.; International Organization for the Study of IBD. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021 Apr;160(5):1570–1583.

P267 Milan Ultrasound Criteria are accurate in assessing endoscopic remission and treatment response in patients with ulcerative colitis

Abstract Background We assessed the accuracy and the responsiveness to change of Milan Ultrasound Criteria (MUC) in patients with ulcerative colitis (UC), using colonoscopy as the reference standard. Methods We performed a prospective observational study of 49 patients with active UC. All patients underwent bowel ultrasound and colonoscopy at baseline and at reassessment, at week 48, after treatment with biologics (29 patients were treated with infliximab, 14 with vedolizumab, four with adalimumab, two with ustekinumab). Furthermore, patients underwent bowel US also at week 12 and 24. Disease activity was quantified using Mayo endoscopic subscore and MUC. The primary analysis was to determine the accuracy of MUC in identification of endoscopic remission defined as a Mayo endoscopic subscore < 2. Additional analyses established the accuracy of MUC in determining change in lesion severity. Logistic regression was used to examine the relationship between the absence or presence (0/1) of endoscopic remission at reassessment as the dependent variable and possible predictors at week 12 as the independent variables. The model was performed using the stepwise backward method. Results Eighteen patients (37%) got endoscopic remission at reassessment. In Table 1 are summarized endoscopic and ultrasound outcomes achieved at reassessment according to the different treatments. MUC < 6.2 determined endoscopic remission with 83% sensitivity, 84% specificity, 84% accuracy, 75% PVP and 90% PVN (Table 2). MUC was sensitive to change in ulcerative colitis [Guyatt’s responsiveness index: 1.73; standardised effect size ratio: 2.0]. MUC changed significantly from baseline to reassessment [8.72 (7.78−9.14) vs 7.60 (4.71−8.53), p < 0.0001], with the largest drop at week 12 [8.72 (7.82−9.19) vs 7.46 (5.80−7.98), p < 0.0001] (Figure 1). A change of -2 in MUC overtime predicted endoscopic remission at reassessment (AUC 0.806, 95% CI 0.667–0.904; sensitivity 89%, specificity 77%). At multivariable analysis only MUC < 6.2 at week 12 was statistically significantly associated with endoscopic remission at reassessment (Table 3). Conclusion MUC accurately detects endoscopic remission. MUC is a highly responsive, reliable tool for assessing treatment response in patients with ulcerative colitis.

P335 Utility of Intestinal Ultrasound in Monitoring Disease Activity in Ulcerative Colitis Patients Treated with Biologics

Abstract Background Given the invasive nature and high cost of frequent and repeated endoscopies needed to monitor UC, search for non-invasive diagnostic alternative is warranted. Intestinal ultrasound is a cost-effective, well-tolerated, non-invasive and readily available „point-of-care“ tool for the management of patients with Crohn’s disease. The role and widespread use of IUS for UC is still limited. We aimed to evaluate association between UC disease activity assessed by IUS on one hand and standard clinical, biochemical, and endoscopic parameters on the other one. Methods A single center, noninterventional retrospective chart review of adult UC patients treated with biologics at a tertiary center was performed. Routine clinical (stool frequency score – SFS, and rectal bleeding score – RBS), biochemical (FC), endoscopic (Mayo Endoscopic Subscore - MES), and IUS parameters (bowel wall thickness - BWT and colonic wall hyperemia assessed by colour Doppler imaging - CDS) were assessed before initiating biologics. Normal distribution was assessed using Shapiro-Wilk tests. Spearman correlation coefficients were calculated and ROC analysis was carried out. Results Total of, 44 patients (50% females, mean age, 37.4 ±, 14.05 years) with predominantly extensive UC (75%) were analysed. Positive correlation was observed between combination of BWT and level of CDS with SFS (rs = 0.68, p <, 0.01, N = 33) as well as with RBS (rs = 0.44, p <, 0.01, N = 34). Moreover FC values were in positive correlation with BWT (rs = 0.54, p <, 0.01, N = 36), levels of CDS (rs = 0.66, p <, 0.01, N = 33) and combination of BWT coupled with level of CDS (rs = 0.7, p <, 0.01, N = 33). In case of clinical active UC (SFS, 2/3 + RBS, 2/3 + FC >150 mg/g) correlation coefficient between FC level and BWT coupled with level of CDS rises to rs = 0.72, p <, 0.01, N = 30. Positive correlation of CDS with MES (rs = 0.65, p <, 0.01, N = 16) as well as between combination of BWT + level of CDS with MES (rs = 0.6, p <, 0.02, N = 16) was observed. Interestingly, positive correlation between BWT and MES didn′t reach statistical significance (rs = 0.42, p = 0.1, N = 16). The area under the curve (AUC) for the FC values and disease activity (defined as SFS, 2/3 + RBS, 2/3 + BWT >4 mm + presence of CDS) was, 0.96 (SE:, 0.03;, 95% CI, 0.89–0.99, p<0.01). FC values >134 mg/g were associated with active disease (sensitivity, 89.3%, specificity, 87.5%). Conclusion Results of this study show a good correlation between IUS and clinical, biochemical and endoscopic parameters of UC disease severity. IUS as a monitoring tool can be helpful in estimation of UC disease activity and can guide daily management of patients treated with biologics.

P218 Accuracy of Ultrasonography in Assessing Disease Activity in Pediatric Ulcerative Colitis: Preliminary Results of a two-center study

Abstract Background Ulcerative colitis (UC) is an inflammatory bowel disease involving rectum and colon. Transabdominal bowel ultrasound (TBUS) is a non-invasive technique evaluating inflamed colonic segments. Previous studies showed optimal concordance between TBUS and endoscopy in the colon, but suboptimal in the rectum. Transperineal ultrasound (TPUS) of the rectum achieved high agreement with endoscopy in adult UC patients. Aim of this study was to assess the accuracy of ultrasound in evaluating disease activity in pediatric UC patients by means of TBUS and TPUS Methods Pediatric UC patients were enrolled in two IBD centers from March to November 2021. Disease activity was determined using PUCAI score and Mayo Endoscopic Subscore (MES). TBUS and TPUS were performed within a week from endoscopy. MES ≤ 1, bowel wall thickness ≤ 3mm in the colon and ≤ 4mm in the rectum were defined as remission. A concordance analysis comparing endoscopy and US was performed. Results Eighteen patients were enrolled with a mean age of 9.1 ± 4.0 years and a mean disease duration of 2 ± 2.9 years.10 patiens had pancolitis, 2 distal colitis, 4 proctitis. Fifteen patients had endoscopic active disease (2 mild, 12 moderate and 1 severe), and 3 were in remission. Good correlation at the Cohen κ-value between endoscopy and TPUS was observed (K= 0.68). In the evaluation of colon with TBUS the same concordance was found in right (K= 0.64), the transverse (K= 0.75) and in the left colon (K= 0.77), while moderate in the sigma (K= 0.55). Conclusion If these results will be confirmed in a larger study, the combination of TBUS and TPUS could represent a non-invasive technique to assess disease activity in UC children.

P128 Accuracy of the combination of transabdominal and transperineal ultrasound for the evaluation of Ulcerative Colitis activity

Abstract Background Transabdominal Bowel Ultrasound (TBUS) is useful technique to assess disease activity and extent in patients with ulcerative colitis (UC); however, the evaluation of the rectum by TBUS is difficult. Recently, transperineal ultrasound (TPUS) has been proposed as a useful diagnostic tool in the evaluation of rectal disease. The aim of the study is to to assess the concordance between the combination of TPUS/TBUS and endoscopy in adult patients with UC. Methods Fifteen consecutive adult patients with UC were prospectively enrolled from June to November 2021. Disease activity was determined using Partial Mayo Score (PMS) and Mayo Endoscopic Subscore (MES). TBUS and TPUS were performed within a week from endoscopy. MES ≤ 1, bowel wall thickness ≤ 3mm in the colon and ≤ 4mm in the rectum were defined as remission. A concordance analysis comparing endoscopy and US was performed by kappa statistics Results Ten patients were male (66%) and 8 female (34%), with a median age of 39± 13,9. Two patients had a pancolitis, 6 a distal colitis, and 3 a proctitis. 4 patients were in remission. The agreement between endoscopy and rectal evaluation with TBUS was fair (k =0.40), while the agreement with TPUS was excellent (k =0.86). The evaluation of the colon with TBUS showed good concordance in the right colon (k= 0.63), left colon (k=0.65), and sigmoid colon (k=0.72), and excellent agreement in the transverse colon (k= 1). Conclusion These preliminary data showed that the combination of TBUS and TPUS allows to easily and accurately study all the segments of the large intestine in patients with UC, overcoming the limitation related to the reduced accessibility to the rectum with only trans abdominal approach.

P542 Topical tacrolimus versus systemic biological therapy for refractory ulcerative proctitis: a retrospective cohort study

Abstract Background Refractory ulcerative proctitis significantly affects patients’ quality of life, because of disabling symptoms such as tenesmus, fecal urgency and rectal bleeding. Immunosuppressive drugs, such as thiopurines and biologics, are recommended by clinical guidelines. Recently, a few studies have suggested that topical tacrolimus can be an effective and safe therapy in inducing clinical remission in these patients. However, there are no comparative data with biologics. The aim of our study was to compare the efficacy and safety of topical tacrolimus versus biological therapy in a retrospective cohort of refractory ulcerative proctitis patients’ followed up in two tertiary IBD clinics. Methods Consecutive patients with refractory ulcerative proctitis who started rectal tacrolimus 2 mg o.d. or biologics were enrolled between 2018 and 2020. Ulcerative refractory proctitis was defined as active disease up to 20 cm beyond the anal verge and endoscopic Mayo score ≥2 failure to both topical and oral mesalamine and corticosteroids. Primary endpoints were clinical response and remission after 8 and 54 weeks of treatment. Secondary endpoints were endoscopic remission after 54 weeks and the rate of adverse events. Clinical response was defined as a decrease in partial Mayo score of ≥3 points, plus either a decrease in rectal bleeding subscore of ≥1 or an absolute rectal bleeding score of ≤1. Clinical remission was defined as a partial Mayo score ≤2, while endoscopic remission as a Mayo endoscopic subscore ≤1. Results 25 patients were enrolled (17 males, mean age 52.0±17.2 years, mean disease duration 11.6±9.0 years, mean partial Mayo score 6.7±1.3; mean endoscopic Mayo score 2.6±0.2). 10 patients were treated with rectal tacrolimus, 15 with biologics (antiTNFs=12; vedolizumab=3). There were no differences at baseline between the two groups. At week 8, 64.0% of patients had a clinical response, while 32.0% obtained clinical remission. At week 54, 80.0% were on clinical response and almost half of the patients were on clinical and endoscopic remission. No significant difference in clinical and endoscopic response and remission rates was observed in the two groups except for a trend toward significance in favour of biologics in the rate of concomitant topical corticosteroid use at 8 weeks (p = 0.06). Two patients experienced biologics related-side effects, while no one had tacrolimus related-ones. Conclusion In this real-world two centers experience, both rectal tacrolimus and systemic biological therapy seem to have comparable efficacy in inducing and maintaining remission in refractory ulcerative proctitis patients. Topical tacrolimus can be a safer and cheaper therapeutic option. Our results need confirmation in prospective and larger studies.

P401 Tofacitinib tissue exposure correlates with endoscopic outcome

Abstract Background Small molecules are being added to the treatment armamentarium of ulcerative colitis (UC). In contrast to monoclonal antibodies, very little is known about their pharmacokinetic-pharmacodynamic profile. We therefore assessed pharmacokinetic-pharmacodynamic changes in Tofacitinib (TFC) treated UC patients, with a focus on STAT3 phosphorylation, as it has been proposed as a marker of efficacy. Methods Thirty UC patients initiating TFC therapy, 10mg BID were prospectively monitored (Table, 1). At week, 8, patients could de-escalate to, 5mg BID or maintain, 10mg BID depending on their response. Endoscopic assessment and sampling (colonic tissue and serum) was performed at baseline and, 8–16 weeks after TFC initiation. Endoscopic improvement was defined as Mayo endoscopic subscore, 0–1. TFC was extracted from tissue using acetonitrile, dried down and quantitated using mass spectrometry. Both total as well as phosphorylated STAT3 were measured in lysed tissue using specific antibodies with an ultrasensitive luminescent oxygen channelling assay. Results TFC tissue and serum concentrations correlated significantly (r=0.92, p<0.001), though were significantly higher in tissue (median, 520.19ng/g vs, 17.35ng/mL, p<0.001). In contrast to TFC serum exposure (p=0.26), TFC tissue exposure at the end of induction was associated with endoscopic improvement by week, 16 (p=0.04) (Figure, 1). In TFC responders (n=14), TFC tissue exposure exceeded the concentration required to block, 90% of the target (IC90) reported in literature (median tissue exposure, 1,055.00ng/g; IC90, 823ng/g). TFC tissue exposure in non-responders (n=16) was lower, but clearly exceeded the IC50. Although IL-6 was not significantly downregulated after TFC induction, a significant decrease in the ratio of mucosal IL-6 driven phosphorylated STAT3 over total STAT3 (pSTAT3/STAT3) was observed in responders (p=0.05), but not in non-responders (p=0.88). The pSTAT3/STAT3 ratio also correlated significantly with faecal calprotectin (r=0.35, p=0.05), but only weakly with the Mayo endoscopic sub score (r=0.22, p=0.13). Baseline mucosal pSTAT3/STAT3 did not differ significantly between future responders and non-responders. Tofacitinib tissue (A) and serum (B) exposure at the end of high dose induction in relation to the achievement of endoscopic improvement at week, 16, defined by a Mayo endoscopic sub-score of, 0–1. Conclusion We could demonstrate for the first time a mucosal exposure-response relationship with TFC in UC patients. Additionally, pSTAT3/STAT3 ratio was identified as potential molecular marker to track response directly linked to the mode-of-action of TFC. Whether an increased local dose of TFC could result in better efficacy without compromising safety should be further explored.

P228 Appendiceal Orifice Inflammation Is Associated with Lower Rate of Complete Endoscopic Remission in Patients with Ulcerative Colitis

Abstract Background Appendiceal orifice inflammation (AOI) is commonly considered a skip lesion in ulcerative colitis (UC). However, the clinical significance of AOI in UC patients remains controversial. This study aimed to evaluate the clinical feature and long-term outcomes of AOI by comparing UC patients with and without AOI. Methods This study was conducted as a retrospective design of patients who were newly diagnosed or referred within 3 months after diagnosis at Seoul St. Mary’s Hospital from January 1, 2001 to December 31, 2020. All patients underwent index and follow-up colonoscopies. The long-term outcomes involved achieving complete endoscopic remission (ER), use of biologics, hospitalization, and proximal disease extension. Complete ER was defined as Mayo endoscopic subscore 0. Results In total, 318 UC patients were included, of which 140 had AOI. The baseline characteristics were not significantly different between AOI and non-AOI groups. The cumulative risk of complete ER was a significant difference between AOI and non-AOI groups (p=0.041). The other cumulative risks of disease outcomes were not significantly different between AOI and non-AOI groups (use of biologics, p=0.542; hospitalization, p=0.795; proximal disease extension, p=0.403). The multivariate Cox regression analysis also revealed that AOI was the only significant factor of complete ER (hazard ratio, 0.636; 95% confidence interval, 0.446–0.906; p=0.012) in UC patients. Conclusion AOI shows a significant association with lower rate of complete ER in UC patients. Therefore, a meticulous treatment strategy may be recommended to achieve complete ER in UC patients with AOI.

P163 Abdominal X-ray: an invaluable tool in Acute Severe Ulcerative Colitis

Abstract Background Intravenous steroids (IV-S) remain the cornerstone of treatment of Acute Severe Ulcerative Colitis (ASUC). However, one-third of these patients are refractory to this treatment. Several indices have been developed to predict the failure of IV-S for ASUC, using clinical data at day 3 of treatment. However, indices able to predict IV-S failure based on admission data are lacking. Methods A retrospective analysis of all consecutive hospital admissions due to ASUC, in a Portuguese tertiary centre, between February 2007 and April 2021 was performed. Only patients receiving IV-S for at least 3 consecutive days were included in this study. IV-S non-response was defined as the need for a second-line therapy or surgery. The following clinical data was collected from each patient: age, gender, disease duration, Montreal disease extension, previous ASUC, previous and on admission medical therapies (oral mesalazine, rectal mesalazine, oral steroids, immunosuppressants and monoclonal antibodies), fever on admission and weeks of symptoms’ worsening before admission. The following parameters on admission were also registered: C-reactive protein, albumin level, hemoglobin, leucocytes count, platelets count, Mayo endoscopic subscore and presence of transverse colonic dilatation on abdominal X-ray ≥5.5 cm. Univariate analysis was used to identify predictive factors of IV-S failure. Results 68 patients (64.7% female), with a mean age of 40.4 (±16.2) years, were included in this study. 9 patients (13.2%) did not respond to IV-S therapy. On univariate analysis, only transverse colonic distension on X-ray was more frequent in IV-S non-responders (33.3% vs 6.8%, p=0.04). Conclusion Clinical data on admission, including previous medication, analytical parameters and endoscopic activity were not predictive of IV-S refractoriness in this population. However, abdominal X-ray showed to be useful to predict the need for a rescue therapy. These findings highlight, in one hand, the need of larger studies to identify on admission predictors of IV-S refractoriness and, in other hand, the importance of abdominal X-ray, in patients admitted due to ASUC.

P430 Longer-term tofacitinib effectiveness for the treatment of ulcerative colitis: Two-year outcomes from a UK observational cohort study

Abstract Background Tofacitinib is an oral small molecule inhibitor licensed for the treatment of ulcerative colitis (UC). Whilst real world data has been presented, outcomes beyond, 26 weeks are limited. The objective of this study was to assess the persistence and long-term effectiveness of tofacitinib. Methods We conducted a retrospective observational cohort study, using a prospectively maintained database, at a large UK IBD tertiary referral centre. The primary objective was to assess the proportion of patients in deep remission at one year. Deep remission was defined as corticosteroid free clinical remission (CSFR) and endoscopic remission (Mayo Endoscopic Subscore (MES) of, 0 or, 1). All adult patients receiving tofacitinib for moderate to severe UC were included from October, 2018 to October, 2021. Disease activity was assessed using the Simple Clinical Colitis Activity Index (SCCAI); clinical response and remission were defined as a reduction of SCCAI ≥3 and a SCCAI ≤2, respectively. All analyses were based on an intention-to-treat principle, and we used non-responder imputation in cases of missingness. Results In total, 103 patients were included with a median follow up duration of, 53 weeks (range, 1–156). Prior to treatment, patients had active disease clinically (median SCCAI, 7 (range, 0–15) and endoscopically (median MES, 3) with, 54% on corticosteroids. The cohort had refractory disease;, 90% were anti-TNF-experienced and, 48% had prior exposure to at least two different biologic classes. Table, 1 shows the baseline characteristics of the cohort and figure 1 shows patient disposition in the study. Median treatment duration on, 10mg bd was, 18 weeks (range, 1–135);, 27% (n=15) were on, 10mg BD at one year and, 11% (n=3) at two years. At, 52 weeks, 61% were in CSFR, 38% in endoscopic remission, and, 36% in deep remission (figure 2). Deep remission was not associated with baseline variables, including prior biologic exposure or disease severity on univariate analyses. Faecal calprotectin fell from median, 451ug/g [range, 5-6020] at baseline to, 86ug/g [range, 5-2360] at week, 52 (n=41, p<0.001), but CRP change was not significant. Three-quarters of those remaining on tofacitinib at, 104 weeks (n=27) were in deep remission. The Kaplan Meier estimated probability of remaining on tofacitinib was, 62% (95% CI, 51–71%) at week, 52 and, 44% (CI, 95%, 32–54%) at week, 104 (figure 3). Conclusion Longer term effectiveness and treatment persistence data in a cohort of highly refractory UC patients is reassuring.

DOP12 Non-invasive assessment of intestinal inflammatory activity in Ulcerative Colitis by Multispectral Optoacoustic Tomography (MSOT)

Abstract Background In order to guide therapy in Ulcerative Colitis (UC), repeated determination of intestinal inflammatory activity is essential. Endoscopy is the standard procedure to assess inflammation in UC. However innovative methods for non-invasive, uncomplicated and risk free estimation of inflammatory activity are needed as bowel preparation, patients discomfort and risk of procedural complications limit the (frequent) use of colonoscopy. Multispectral optoacoustic tomography (MSOT) is a promising new method to measure inflammation in UC. Using short and harmless impulses of NIR-lasers, it allows for determination of a specific hemoglobin-signal in the bowel-wall and therefore inflammatory activity in affected bowel segments. However, its informative value in UC has not been evaluated so far. Methods In 34 patients with confirmed UC, clinical activity parameters (e.g. clinical Mayo-Subscore, B-mode-sonography, C-reactive protein, white blood count) were collected and MSOT of the sigmoid was performed within 2 weeks before/after endoscopy. For MSOT, a commercially available clinical MSOT-system (Acuity Echo, iThera Medical, Munich) was used with sequential analysis of collected data on an external desktop PC. Finally, clinical data, ultrasound findings (Limberg) and MSOT-parameters (single wavelenghts 760 nm, 800 nm, 900 nm; multispectral signals hb, hbO2, hbT) were correlated with endoscopic findings (Mayo endoscopic Subscore, MES). Results We found strong and significant correlation between MES and MSOT parameters 800 nm (Spearman r = 0,6599; p < 0,0001) and HbO2 (Spearman r = 0,6695; p < 0,0001), superior to sonographic evaluation of the inflammatory activity in affected bowel segments (Spearman r = 0,4914; p = 0,0023). Simultaneously these MSOT parameters demonstrated excellent sensitivity and specifity in distinguishing moderately to highly active (MES 2,3) from inactive and mild disease (MES 0,1) (800nm: AUROC 0,9063 (p < 0,0001); sensitivity = 93,75 %, specificity = 88,89 %; HbO2: AUROC 0,9063 (p < 0,0001); sensitivity = 100 %, specificity = 88,89 %). Conclusion MSOT is a promising approach to non-invasively assess intestinal inflammation in UC and therefore monitor anti-inflammatory therapy in these patients. Further studies are required to validate these findings.

DOP17 Evaluating segmental healing with the modified Mayo endoscopic score (MMES) has a clear additional value in predicting long-term outcome in patients with Ulcerative Colitis: Results from a prospective cohort study

Abstract Background Most endoscopic scoring systems (including the Mayo endoscopic subscore, MES) do not consider the extent of inflammation and can therefore not pick up segmental endoscopic improvement. The modified Mayo endoscopic score (MMES) was developed to overcome this limitation. We examined the predictive value of the MMES in addition to the MES on long-term clinical outcome in ulcerative colitis (UC). Methods Between 2014 and 2017, patients initiating biologic therapy for active UC (baseline MES ≥2) were recruited. Patients without assessment of the upper margin of inflammation or with a clinical follow-up <12 months were excluded. We conducted a clinical and endoscopic assessment at baseline and week 8 (adalimumab, ADM) or 14 (golimumab, GOL; infliximab, IFX; vedolizumab, VDZ). Clinical response was defined as a decrease in the adapted Mayo score (excluding physician global assessment) with ≥2 points and ≥30%, plus a decrease in rectal bleeding score ≥1 or an absolute rectal bleeding score ≤1. We classified patients by evolution of endoscopic activity at week 8/14 in group A (endoscopic healing, MES ≤1), group B (segmental healing, MES >1 but decrease in MMES ≥30%) and group C (MES >1 and no drop in MMES ≥30%). Clinical relapse-free, discontinuation-free and colectomy-free survival was estimated by Kaplan-Meier analysis with log-rank test. Results A total of 150 UC patients were included (52% male, median age 42 years, median disease duration 7 years) with a median (IQR) follow-up of 61 (48–68) months. An anti-TNF was initiated in 74 (35 IFX, 23 ADM, 16 GOL), and VDZ in 76 patients. A significant reduction in MES and MMES was observed at week 8/14 (cf. table). In group A 67/69 (97%) patients achieved clinical response compared to 15/27 (55%) in group B and 11/54 (20%) in group C. During follow-up 60/93 (65%) patients maintained clinical response, 83/150 (55%) patients discontinued treatment due to primary non-response or loss of response and 33/150 (22%) patients underwent colectomy. The ΔMMES demonstrated to be of additional predictive value: there was a significant difference between groups B and C regarding clinical relapse, drug persistence and need for colectomy (cf. figure). Conclusion Although MES ≤1 remains the best predictor of long-term outcome, the MMES - identifying a subgroup with a segmental endoscopic response - demonstrated a clear additional value predicting long-term outcome in UC. These promising results merit inclusion of the MMES in future clinical trials. Table The MMES is calculated by multiplying the Mayo endoscopic subscore for the different colon segments with the maximal extent of inflammation (in decimeters) divided by the number of segments with active inflammation (Lobatón T, et al. JCC 2015; 9:846–52.) Figure

OP23 The efficacy and safety of guselkumab induction therapy in patients with moderately to severely active Ulcerative Colitis: Phase 2b QUASAR Study results through week 12

Abstract Background The QUASAR Induction Study 1 (NCT04033445) is a phase 2b randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of guselkumab (GUS), an interleukin-23 p19 subunit antagonist, as induction therapy in patients with moderately to severely active ulcerative colitis (UC) who had an inadequate response or intolerance to conventional (ie, thiopurines or corticosteroids) or advanced therapy (ie, tumor necrosis factor alpha antagonists, vedolizumab, or tofacitinib). Methods Patients included in these analyses had moderately to severely active UC (defined as a modified Mayo score of 5 to 9, inclusive) with a Mayo rectal bleeding subscore ≥ 1 and a Mayo endoscopy subscore ≥ 2 obtained during central review of video endoscopy at baseline. Patients were randomized 1:1:1 to receive IV GUS 200 mg, 400 mg, or placebo at Weeks 0, 4, and 8. The primary endpoint was clinical response at Week 12, and major secondary endpoints included clinical remission, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization at Week 12. Type 1 error was controlled at the 0.05 significance level for the primary endpoint; no other endpoints were controlled for multiplicity. Safety was assessed through Week 12. Results Three hundred thirteen patients were randomized in the primary analysis population (mean age, 41.6 yrs; male 59.1%, mean UC duration, 7.55 yrs; mean Mayo score, 9.2; endoscopy subscore of 3 indicating severe disease, 70%; baseline oral corticosteroid use, 39.6%). Approximately 50% had a prior inadequate response or intolerance to advanced therapy for UC. The baseline demographics and disease characteristics were generally similar among treatment groups (Table 1). At Week 12, a significantly greater proportion of patients treated with GUS 200 mg and 400 mg achieved clinical response compared with placebo (61.4% and 60.7% vs 27.6%, respectively, both p<0.001). A greater proportion of GUS-treated patients compared with placebo-treated patients achieved the major secondary endpoints at Week 12 (Figure 1). The proportions of patients reporting adverse events, serious adverse events, and adverse events leading to discontinuation in the GUS groups were not greater compared with placebo (Table 2). No serious infections were reported for GUS. No cases of malignancy or death were reported. Conclusion In patients with moderately to severely active UC, GUS induction treatment demonstrated superior efficacy compared with placebo treatment. Overall, safety results through Week 12 were consistent with the known safety profile of GUS in approved indications. The efficacy and safety of GUS 200 mg and 400 mg were comparable.

P221 Association between Irritable Bowel Syndrome-type symptoms and Ulcerative Colitis: is it real?

Abstract Background The origin of gastrointestinal symptoms compatible with irritable bowel syndrome (IBS) in patients with inflammatory bowel disease in remission is a challenge. Our aim was to prospectively determine the relation of IBS symptoms with calprotectin levels (FC), endoscopic Mayo score and histologic findings, in patients with ulcerative colitis (UC) in clinical remission. Methods Patient recruitment was between January – March of 2020 and November of 2020 - August of 2021 and included consecutive UC patients in clinical remission and scheduled for a colonoscopy. Clinical remission was defined by a stool frequency ≤3/day with no bleeding, ulcerative colitis activity index <4 and serum C-reactive protein lower than 1mg/dL. Exclusion criteria were therapeutic with corticosteroids over the prior 6 months or initiation of biological agents in the last 6 months. IBS diagnosis was evaluated by Roma IV criteria (IBS-like group). FC level was assessed before colonoscopy and during the exam Mayo endoscopy subscore was applied and random biopsies of all segments of colon and rectum were made to achieve histologic activity using Geboes index. This study was approved by Centro Hospitalar e Universitário de Coimbra Ethics Committee. Results A total of 106 patients (50% women; mean age 51 years ±14.8) were included. The mean of disease duration was 15.7 years (±9.06) and 13 of them (12.3%) had proctitis, 64 (60%) left-sided colitis and 29 (27.4%) extensive colitis. Regarding disease activity: mean FC was 189.48mg/Kg (±382), endoscopic Mayo score lower than 1 was found in 63 patients (59.4%) and Geboes index lower than 1.1 was found in 66 patients (62.3%). Rome IV criteria for IBS were fulfilled by 29 patients (27.4%). The IBS-like group showed FC levels significantly higher (303±483mg/Kg vs. 139±319mg/Kg; P<0.05), with greater histologic activity (Geboes index >1.1 in 65,5% vs. 27.3%, P<0.05). Besides, in the same group (IBS-like group), Mayo endoscopy subscore was numerical higher but with no statistical significancy (subscore ≥1: 55.2% vs. 36.4%; P>0.05). Conclusion IBS-like symptoms are common in patients with UC considered to be in clinical remission. Higher levels of FC and histological activity support the idea of the presence of subclinical inflammation rather than coexistent IBS.

DOP55 Long-term outcomes after histologic-endoscopic mucosal healing: Results from the UNIFI study in Ulcerative Colitis

Abstract Background In the UNIFI study of ustekinumab (UST) in ulcerative colitis (UC), patients who achieved histo-endoscopic mucosal healing (HEMH; ie, both histologic and endoscopic improvement of mucosa) after induction had higher clinical remission and corticosteroid-free clinical remission rates through 1 year than those who achieved either histologic or endoscopic improvement alone.1 Here, we report the effect of achieving HEMH after induction on long-term symptomatic outcomes through 3 years. Methods Patients who were in clinical response after 8 wks of IV induction with UST 130mg or ~6mg/kg (wk 8 responders) were randomized to maintenance treatment with SC UST 90mg q12w or q8w on entry into maintenance. Those who were not in clinical response to the initial UST dose at wk8 but achieved response at wk16 after receiving a single SC dose of UST 90mg at wk8 (wk16 responders) entered maintenance receiving SC 90mg q8w. After 44 wks of maintenance treatment, patients were given the option to continue in the long-term extension. HEMH was defined as achieving both endoscopic improvement (Mayo endoscopy subscore ≤1) and histologic improvement (neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue; based on the Geboes score). Patients with insufficient data for histologic evaluation at the end of induction were excluded. Symptomatic remission was defined as a Mayo stool frequency subscore of 0 or 1 and a Mayo rectal bleeding subscore of 0. Results Of the 438 patients who were wk8 or wk16 responders to UST induction and received UST maintenance, 116 (26.5%) achieved HEMH after induction, 30 (6.8%) achieved endoscopic improvement without histologic improvement (EI), and 106 (24.2%) achieved histologic improvement without endoscopic improvement (HI). Patients who achieved HEMH after induction had higher symptomatic remission and corticosteroid-free symptomatic remission rates at wks92 and 152 than those with EI or HI; the differences were statistically significantly greater at wk152, while they were only numerically greater at wk92 (Table). The differences were primarily driven by patients with HEMH after induction being more likely to maintain symptomatic remission between wks92 and 152, than those with EI or HI alone. Symptomatic remission and corticosteroid-free remission rates decreased between wks92 and 152 in patients with EI or HI only. Conclusion Patients with UC who achieved HEMH after induction with UST were more likely to maintain symptomatic remission and corticosteroid-free symptomatic remission between 2 and 3 years of maintenance treatment than those who achieved EI or HI alone. Reference 1. K Li, et al. Poster 1008. Presented at UEGW 2019. October 22, 2019. Barcelona, Spain.

P708 Ileal involvement defined by Montreal classification in Crohn’s disease is associated with a distinct microbial composition in ileal and colonic mucosa

Abstract Background The Montreal classification of inflammatory bowel disease (IBD) recognizes distinct subgroups based on location of disease, age at onset and behaviour for Crohn’s disease (CD) and extent in ulcerative colitis (UC). CD with ileal involvement is in part genetically determined and tends to progress to surgery and to be more refractory to medical therapy compared to colonic disease location. We investigated the association of different aspects of the Montreal classification with the ileal and colonic mucosa-associated microbiota. Methods Healthy control (HC) and IBD patients underwent colonoscopy with biopsy samples taken from terminal ileum, ascending and sigmoid colon. Mucosal 16s rRNA gene profiling was analysed and an amplicon sequence variant table was generated and normalized. Patients with prior intestinal resection, IBD-unclassified and recent antibiotic exposure were excluded. Endoscopic activity was defined as a segmental Mayo endoscopic subscore > 0 in UC and a simple endoscopic score > 2 in CD. Blood samples were drawn for genotyping and a weighted genetic risk score (GRS) was built based on 169 IBD risk variants. Pooled ileal and colonic samples were analysed for taxonomic differential abundance (DA) among the variables of the Montreal classification using a linear mixed-effects model (MaAsLin2) with age, sex, biopsy site, endoscopic activity and GRS as covariates. P-values were corrected for false discovery rate (FDR) and < 5% was considered significant. Results A total of 546 biopsy samples from 201 IBD patients and 48 HC were analysed. The characteristics of the cohort and Montreal classification are depicted in the Table. At colonoscopy 168 samples (31.4%) showed endoscopic activity. The multivariate analysis revealed that the genera Agathobacter and Faecalibacterium, as well as the family Ruminococacceae and the order Oscillospirales were significantly reduced in CD with ileal involvement (L1+L3) when compared to either isolated colonic CD (L2), UC (any extent) and HC independent of age, sex, endoscopic activity, biopsy site, and GRS (Figure). Samples from UC and isolated colonic CD patients did not show differences in their microbial profile irrespective of biopsy site. No differences in DA were observed in subgroups based on age at onset and disease behaviour in CD or extent in UC. GRS was not associated with microbial composition. Conclusion These data suggest that CD with ileal involvement (Montreal L1+L3) is a major determinant of the tissue-associated microbial composition in both ileal and colonic mucosa irrespective of variables such as endoscopic activity and GRS. The reduction of several beneficial microbes in CD with ileal involvement might partially explain the more progressive phenotype in such patients.

P292 Association of golimumab trough concentrations during maintenance with endoscopic and histologic remission in patients with ulcerative colitis

Abstract Background The aim of this study was to investigate the association of serum golimumab concentrations (SGC) during maintenance therapy in UC with clinical outcomes including endoscopic and histologic healing. Methods This multicentre, cross-sectional cohort study included UC patients who had received at least 5 maintenance doses of golimumab. A colonoscopy was scheduled, and study-specific recto-colonic biopsies were taken for blind central histologic reading. Samples for trough SGC and anti-golimumab antibodies (AGA) were collected on the day of the scheduled golimumab administration closest to the colonoscopy. Definitions: clinical remission = partial Mayo score (PMS) ≤2 with no individual subscore >1, combined clinical-biochemical remission = PMS ≤2 + faecal calprotectin <300 μg/g, endoscopic healing = Mayo endoscopic subscore of 0, deep remission = clinical remission + endoscopic healing, histologic remission = Geboes index ≤2.0, and disease clearance = clinical remission + endoscopic healing + histologic remission. Results Fifty-two patients were included. The overall median SGC was 1.79 µg/ml (interquartile range [IQR] 0.87–2.79). Three patients (5.7%) had undetectable SGC together with positive AGA. With a median of 23 [IQR 15–32] months of golimumab therapy, 46 patients (88%) were in clinical remission, 26 (52%) had combined clinical-biochemical remission, 18 patients (35%) had both endoscopic healing and deep remission, 21 (40%) had histologic remission, and 14 (27%) had disease clearance. Median SGC were significantly higher in patients who were in clinical remission (2.01 versus 0.72 µg/mL, P=0.047) µg/mL, combined clinical-biochemical remission (2.21 versus 1.47 µg/mL, P=0.041), mucosal healing and deep remission (2.52 versus 1.47 µg/mL, P=0.003), histologic remission (2.33 versus 1.50 µg/mL, P=0.02), and disease clearance (2.52 versus 1.70 µg/mL, P=0.009), compared with those not meeting these criteria. (Figure 1) The higher SGC quartiles were associated with higher rates of mucosal healing (P=0.005), and histologic remission (P=0.006). (Figure 2) Receiver-operating characteristic analyses identified SGC thresholds [area under the curve] of 0.85 [0.76], 1.90 [0.65], 2.29 [0.75], and 2.29 [0.72] µg/mL be associated with clinical remission, combined remission, deep remission, and disease clearance, respectively. (Table 1) On multivariate analysis, body mass index (P=0.021) and CRP level (P=0.040) were linearly associated with lower SGC, and concomitant immunosuppressant with higher SGC (P=0.47). (Table 2) Conclusion We identified SGC thresholds during maintenance most closely associated with clinical outcomes including endoscopic and histologic healing. Higher SGC are needed to achieve increasingly stringent therapeutic targets.

OP26 Efficacy and safety of mirikizumab as induction therapy in patients with moderately to severely active Ulcerative Colitis: Results from the Phase 3 LUCENT-1 study

Abstract Background Anti-IL23p19 inhibitors are emerging as promising treatment options for ulcerative colitis (UC). Mirikizumab (miri) is a humanized, IgG4 monoclonal antibody directed against the p19 subunit of IL-23, a key mediator in the pathogenesis of inflammatory bowel diseases. We assessed the induction efficacy and safety of miri with a Phase 3, multi-center, randomized, parallel-arm, double-blind, placebo (PBO)-controlled trial (LUCENT 1; NCT03518086) in patients with moderately to severely active UC (Modified Mayo Score 4–9 points and centrally read Mayo endoscopic subscore ≥2) who had inadequate response, loss of response, or intolerance to corticosteroids, immunosuppressants, biologic therapies, or tofacitinib. Methods Adult patients (N=1281) were randomized in a 3:1 ratio to receive blinded intravenous administration of 300 mg miri or PBO every 4 weeks for 12 weeks. Randomization was stratified by biologic failure status, baseline (BL) corticosteroid use, BL disease activity as measured by modified Mayo score, and world region. The primary objective was to test the hypothesis that miri was superior to PBO in inducing clinical remission at Week 12. Key secondary objectives were clinical response, endoscopic remission, symptomatic remission, clinical response in biologic-failed patients, histologic-endoscopic mucosal improvement, and improvement in bowel urgency at Week 12 (see Figure for endpoint definitions). Mixed Model for Repeated Measures was used to assess urgency; the Cochran-Mantel-Haenszel test, with missing data imputed as nonresponse, was used to assess all other outcomes. Results BL characteristics were balanced across the two treatment groups. A significantly greater proportion of patients treated with miri achieved clinical remission at Week 12 (Miri: 24.2%; PBO: 13.3%; Δ=11.1 [99.875%CI: 3.2, 19.1]; p=0.00006). Miri-treated patients achieved all key secondary endpoints, including a significantly greater average reduction in bowel urgency severity compared to PBO (p<0.00001). The frequencies of treatment-emergent adverse events in miri-treated patients were similar to PBO. There were numerically fewer serious adverse events (Miri: 27 [2.8%], PBO: 17 [5.3%]) and discontinuations due to adverse events (Miri: 15 [1.6%], PBO: 23 [7.2%]) in miri-treated patients compared to PBO. There were 2 colon malignancies in the miri arm (0.2%) and no deaths during the treatment period. Conclusion In this phase 3 UC study, 300mg miri IV demonstrated statistically significant and clinically meaningful improvements vs PBO in all primary and key secondary endpoints across clinical, endoscopic, histologic, and symptomatic measures, with an acceptable safety profile.