Rectal Bleeding Score Research Articles

P1015 Upadacitinib as a Rescue Therapy in Patients with Steroid- and Infliximab-Refractory Acute Severe Ulcerative Colitis: Real-Life Multicentre Results

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease with remissions and flares. Approximately 20% of UC Patients develop acute severe ulcerative colitis (ASUC), a serious condition that is refractory to standard therapies and leads to morbidity and mortality. Rescue therapy (salvage therapy) with steroids, cyclosporine, and/or infliximab is recommended by guidelines.1 The colectomy rate in ASUC remains at around 36% even in the biological millennium.2 Upadacitinib (UPA) is a JAK1 selective inhibitor used effectively to treat UC. The role of UPA as a rescue therapy in ASUC is not clear. This study aims to evaluate the outcomes of UPA as a rescue therapy in ASUC patients. Methods A total of 31 steroid- and infliximab-refractory ASUC patients from 10 IBD centers from all over Türkiye were included between April 2023 and October 2024 in our study. Demographics of the patients and disease characteristics were recorded. Stool frequency (per day), rectal bleeding scores, and C reactive protein (CRP) were assessed from the electronic database at baseline (week 0), week 1, 4, 8, and 16 retrospectively. Complete clinical response was defined as stool frequency ≤3 per day and rectal bleeding score 0-1. Results Mean age was 36±13years; 16(51.6%) were female, mean disease duration was 6.9±5.4 years, 30(96.8%) had immunomodulator experience (Table1). A total of 10 patients had ≥ 3 biologics failures. Complete clinical response at weeks, 4, 8, and 16 were in 13 (42%), 16 (64%), 12 (67%), and 10 (77%) patients respectively. Rescue therapy responses were not statistically significant between ≥3 and <3 biologics failure groups (p=0.580) at week1. CRP normalization (<3 mg/L) at week 4 was found in 9(36%) patients. By the end of the week, 6 (33%) patients had undergone colectomy. Clinical responses and surgery rates of UPA at week1,4,8, and 16 were detailed in Figure 1. Conclusion UPA provided a complete clinical response as a rescue therapy within the first week in 42% of cases in anti-TNF and steroid non-responders even with multiple biologics experience. Over half of the patients showed clinical remission by weeks 4 and 8.

P0772 Efficacy and consumption of golimumab is similar with European and American dosing regimens in Ulcerative Colitis: Results of a prospective study

Abstract Background Golimumab is a subcutaneous TNF-alpha inhibitor approved for ulcerative colitis in European Union (EU) and United States of America (US). Interestingly, maintenance dose for patients weighing ≤80 kg is different in EU and US. In EU, golimumab maintenance dose in 50 mg every 4 weeks with an option of reactive dose escalation to 100 mg every 4 weeks in case of inappropriate response. In US, maintenance dose is 100 mg every 4 weeks for all patients, irrespective of body weight and response to induction. Here we compared efficacy, safety and drug consumption of EU and US maintenance dosing of golimumab in patients weighing ≤80 kg. Methods In this investigator initiated prospective study (ClinicalTrials.gov ID: NCT04156984) we recruited 29 patients with active ulcerative colitis. After common induction (golimumab 200 mg at baseline and 100 mg at week 2) all patients received 1 year of maintenance treatment. First 15 patients received US maintenance regimen with 100 mg golimumab monthly and next 14 patients received EU maintenance regimen with 50 mg golimumab monthly. Those in EU regimen with inadequate response to induction or loss of response during maintenance phase (rectal bleeding score (RBS) > 0 or endoscopic Mayo score (eMayo) ≥ 2) increased dose of golimumab from 50 mg to 100 mg. Co-primary endpoints were endoscopic improvement (eMayo ≤ 1) at weeks 14 and 50 and clinical remission (RBS = 0 and stool frequency score (SFS) < 2) at weeks 14, 26, 38, and 50. Statistical analysis included Chi-square and Mann-Whitney tests. Results Patient demographic data are shown in Table 1. Endoscopic improvement and clinical remission rates were similar with EU and US maintenance regimens (Figure 1). 8/14 (57%) of patients in EU regimen needed dose escalation to 100 mg due to inadequate response after a median of 8.6 weeks (interquartile range 6 to 14 weeks). Drug persistence and drug consumption was similar in both maintenance regimens (Figure 1). In the US regimen 3 potentially drug-related side effects occurred (one case each: one-dermatome herpes zoster, labial herpes, skin small vessel vasculitis), but none in the EU regimen. Conclusion In this prospective study, EU and US golimumab maintenance regimens resulted in similar endoscopic improvement and clinical remission rates during the first year of treatment with golimumab in patients with ulcerative colitis weighing ≤80 kg. Due to high dose escalation rates in EU regimen dose consumption was similar in both maintenance regimens.

OP31 Phase 1b study of SOR102, a novel, orally delivered bispecific anti-TNF/anti-IL-23 domain antibody in patients with mild to severe ulcerative colitis

Abstract Background SOR102 is a novel, orally delivered, bispecific antibody construct containing two humanized single domain antibodies (SDA) targeting TNFα and IL-23p19 connected by a trypsin-labile linker, enabling monomer separation within the small intestine and inhibition of TNFα and IL-23 activity within GI tissue. SOR102 SDAs were engineered for stability to intestinal and inflammatory proteases. The Phase 1, first-in-human study (SOR102-101; NCT06080048) had 3 parts. Parts 1 and 2 enrolled healthy subjects. Here, we present results for Part 3, a Phase 1b randomized, double-blind, placebo-controlled study in patients (pts) with mild to severe UC. Methods Pts with Mayo endoscopy score (ES) ≥2, rectal bleeding score (RBS) ≥1 and stool frequency score (SFS) ≥1 were randomized 1:1:1 to receive SOR102 810mg BID, SOR102 810mg QD, or placebo for 6 weeks. The primary objective was safety and tolerability of SOR102. Secondary objectives were the concentration of SOR102 and monomers in serum, urine and feces, and antidrug antibodies. Exploratory efficacy endpoints were Mayo Score (MS) and modified MS (mMS) clinical response, symptomatic remission (SR), and mean change from baseline in MS, mMS, UC-100 score, SFS, RBS, fecal calprotectin (FC), C-reactive protein (CRP), and Robarts Histopathology Index (RHI). Safety and efficacy were evaluated in pts who received ≥1 dose of SOR102 or placebo. Efficacy was also evaluated in pts who completed the study. Results Twenty-two pts were randomized (SOR102 810mg BID=9; SOR102 810mg QD=7; placebo=6); 17 pts completed the study. Reasons for discontinuation were worsening of UC (N=2), study schedule non-compliance (N=2) and consent withdrawal (N=1). Mean age was 50 yrs; 45% were male; median MS was 8 (range 6-11). Most pts were advanced therapy-naïve. TEAEs were reported in 57%, 29%, and 50% of pts receiving SOR102 810mg BID, SOR102 810mg QD, or placebo, respectively (Table 1); most were mild-to-moderate in severity. One AE (SOR102 810mg BID arm) was considered possibly related to SOR102 (abdominal pain of mild severity). One serious AE of worsening of UC that led to hospitalization occurred in the SOR102 810mg BID arm. Figure 1 shows exploratory efficacy results. Higher rates of MS and mMS clinical response and SR, and greater decreases from baseline in MS, mMS, UC-100, combined SFS+RBS, and RHI were observed in the SOR102 BID arm compared with QD and placebo. There were no significant differences in FC and CRP between the treatment groups. Conclusion SOR102 was safe and well tolerated. Efficacy across multiple endpoints was observed in the SOR102 BID arm compared to QD and placebo, despite the short treatment duration. Further clinical development of SOR102 is warranted.

P1130 Real-life histological remission in Ulcerative Colitis patients treated with Ustekinumab: results from the Belgian SULTAN trial

Abstract Background Histological remission is an aspirational therapeutic target in Ulcerative Colitis (UC) associated with lower relapse rates.1Ustekinumab (UST), a monoclonal antibody against the p40 subunit of interleukin (IL) 12 and 23 has shown in the UNIFI trials to be effective and safe in patients with moderate-to-severe UC. However, real-life data on histological remission rates are sparse. The aim of the study was to assess the real-life histological response and remission rates of UST in patients with UC across Belgian hospitals. Methods In this multicentric, retrospective observational study, patients with UC who initialised UST treatment between September 2020 and July 2023 were included. Histological remission was defined as Nancy score = 0, response as Nancy ≤ 1 and assessed at week 16 and 52 by the local pathologist. Other endpoints included steroid-free clinical remission (partial Mayo ≤ 2 with no subscore >1), endoscopic remission (endoscopic Mayo = 0), endoscopic response (Mayo score ≤ 1) and clinical response (decrease in partial Mayo score ≥ 3 points and ≥ 30% plus a decrease in rectal bleeding score ≥ 1 or an absolute rectal bleeding score ≤ 1). UST drug persistence was analyzed by Cox regression analysis, predictors of other endpoints by logistic regression. Results 120 patients with moderate to severe UC (86% patients with ≥S2 severity) were included across 16 participating centers. Median disease duration was 11 years (IQR 9) and 81 (68%) of patients had previously failed 2 or more biologicals. Histological remission was achieved in 3/37 (8%) and 5/45 (11%) at W16 and W52, while histological response was seen in 10.8% (4/37) and 26.7% (12/45) respectively. Steroid-free clinical remission rates were 41/120 (34%) and 38/85 (44%) while endoscopic remission was seen in 23/120 (19%) and 13/52 (25%) at W16 and 52 respectively. Two patients (40%) in histological remission at W52 had an endoscopic Mayo 0 score, while 3 had a Mayo 1 (60%) at the time of evaluation. Active smoking was a negative predictor for achieving steroid-free remission (OR 0.412, p=0.011). No significant predictors for histological remission or response could be identified. UST drug persistence by week 52 was 70.8%. Active smoking (OR 3.058, p=0.02), vedolizumab non-response (OR 2.592, p=0.03) and a high Nancy baseline score (OR 2.46, p=0.04)) were associated with UST failure Conclusion In this multi-centric, real-life cohort with highly refractory UC patients, UST shows acceptable clinical and endoscopic remission rates, but histological remission rates remain low after one year of treatment.

P0347 Correlation between histologic disease activity in the distal and proximal colon in Ulcerative Colitis: A flexible sigmoidoscopy is insufficient to assess histology

Abstract Background Ulcerative Colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing inflammation of the colon. Current therapeutic goals emphasize clinical and endoscopic remission; however, histological remission has emerged as an important target due to its association with reduced relapse rates and improved long-term outcomes. Despite this, limited data exist on the concordance of histological activity between colonic segments, especially in UC patients in clinical remission. This study investigates the correlation between histological disease activity in the rectosigmoid colon (RSC) and other colonic segments in patients with UC in clinical remission. Methods This prospective study analyzed data from 203 UC patients in clinical remission, defined as a partial Mayo score ≤2 and rectal bleeding score = 0 for at least three months. Colonoscopies with segmental biopsies were performed, and histological activity was assessed using the Geboes score. Histological remission was defined as a Geboes score <2A.0, while active disease was classified as ≥3.1. Correlation between histological activity in the RSC and other colonic segments was evaluated using Spearman’s correlation coefficients and logistic regression. Statistical significance was defined as p < 0.05. Results Among the 203 patients, the median age was 45 years, with 55.1% having pancolitis. Histological activity in the RSC showed poor correlation with other colonic segments. In patients with a RSC Geboes score of ≥3.1, the correlation coefficient between the RSC and descending colon was 0.05 (p = 0.62), between the RSC and transverse colon was -0.03 (p = 0.71), and between the RSC and right colon was 0.12 (p = 0.09). In patients with a RSC Geboes score of <2A.0, the correlation coefficient between the RSC and descending colon was 0.12 (p = 0.22), between the RSC and transverse colon was 0.05 (p = 0.59), and between the RSC and right colon was 0.18 (p = 0.01). Even among patients with pancolitis, histological concordance between segments remained low. These findings underscore substantial segmental variability in histological activity. Conclusion Flexible sigmoidoscopy (FS) is commonly used to monitor UC due to its practicality; however, our findings suggest FS may not reliably reflect proximal histological disease. The lack of concordance highlights the limitations of FS in accurately assessing histological remission, including in patients with pancolitis or extensive colitis. Full colonoscopy with segmental biopsies remains the gold standard for comprehensive disease evaluation and management. Further research is warranted to refine histologic assessment strategies in UC.

P1065 Rapid onset of action of ustekinumab in patients with moderate to severe Ulcerative Colitis (RAUCU Study)

Abstract Background Real-world data on the speed of onset of ustekinumab (UST) in patients with ulcerative colitis (UC) are limited. Current information regarding early response in these patients comes from the UNIFI trial. The primary outcome of this study was to evaluate the response to UST in patients with moderate-to-severe UC by assessing PRO2 at 14 days after the first intravenous dose (6mg/kg). Methods A multicenter, prospective observational study was designed in patients ≥18 years old with moderate-to-severe UC (partial Mayo score ≥6) who initiated UST 6mg/kg between June 2023 and September 2024. Patients received a diary to record the stool frecuency and rectal bleeding during first 14 days after first dose of induction. The proportion of patients achieving the combined outcome of rectal bleeding score = 0 and stool frequency score ≤ 1 (PRO-2: patient-reported outcome 2 remission) was assessed. FC was measured at baseline and at day 7 and 14. Health-Related Quality of Life was evaluated using the disease-specific shortened Spanish version of the IBDQ (SIBDQ-9) at baseline and at 4 weeks. Patients with previous panproctocolectomy with ileostomy or pouch and those who had received cyclosporine within one month prior to starting UST were excluded. Descriptive statistics are presented as frequencies with percentages for categorical variables. Results A total of 54 patients were included across 14 hospitals in Spain. Of these, 29 (53.7%) were men, with a mean age of 54 (± SD 16.1) years. Thirty (55.6%) patients had pancolitis, 20 (37%) had left-sided colitis, and 4 (7.4%) had proctitis. Five (9.3%) patients were bio-naïve, 32 (59.3%) had previously received one biological therapy, 10 (18.5%) had received two, and 7 (13%) had received three biologics prior to starting UST. Mean decreases in stool frequency and rectal bleeding are shown in Figure 1. By day 14, 26% of patients had achieved clinical remission. No significant differences in clinical remission were observed based on disease extent (p = 0.11) or the number of prior biologics (p = 0.39). By day 7, 12/31 (38.7%) patients with baseline bloody stools had achieved a rectal bleeding score = 0. A reduction in FC >50% was observed in 14/48 (29%) patients by day 7 and in 20/47 (43%) patients by day 14. The SIBDQ9 average score was 54.9 (± SD 6.2) at baseline and 61.3 (± SD 7.4) at week 4. Conclusion One-quarter of patients with moderate-to-severe UC achieved clinical remission by day 14 following the first induction dose of UST. Nearly 40% of patients achieved a rectal bleeding score = 0 (PRO2) by day 7. A reduction in FC >50% was observed in 43% of patients by day 14.

P0420 Interim analysis of real-world-data on PROs and biomarker remission collected through the Health Outcome Observatory (H2O) consortium in IBD patients

Abstract Background The Health Outcome Observatory (H2O) project aims to standardize and facilitate the collection of patient reported outcomes (PROs) and clinical outcomes by Core Outcome Sets (COS) in patients with inflammatory bowel disease (IBD).1 The present study describes preliminary data on clinical and biomarker remission as well as quality of life. Methods This is a real-world interim analysis of IBD patients included in the H2O project at the Medical University of Vienna, Austria, and the Hospital Universitari Vall d’Hebron, Barcelona, Spain. The variables analyzed were part of the COS. Clinical remission was defined by PRO-2 (for Crohn’s disease (CD): number of liquid or very soft stools ≤3, abdominal pain score ≤1; for ulcerative colitis (UC): rectal bleeding score=0, stool frequency score ≤1), biomarker remission by faecal calprotectin (<150g/g) and C-reactive protein (<0.5mg/dl), and quality of life by PROMIS_10_Q02 (quality of life answered as very good or excellent). Co-primary endpoints were clinical and biomarker remission and a very good or excellent quality of life. A descriptive analysis was performed. Results 532 patients were included in Austria (221 female [42%]; 298 CD, 178 UC, 6 IBDU, 50 with missing diagnosis) and 30 in Spain (14 female [47%]; 18 CD, 12 UC). 138 of 532 patients in Austria (26%) did not provide PRO data. The majority of patients were on advanced therapies (CD: 221/298; 77%; UC: 118/178; 66%). Among CD patients 175 were in PRO-2 remission in Austria (80%) and 13 in Spain (72%), the corresponding numbers of patients in UC PRO-2 remission were 86 in Austria (62%) and 11 in Spain (92%). Biomarker remission was observed in 128/240 CD patients (53%) and 84/135 UC patients (62%). Detailed results of the PRO-2 and of the biomarker values of the Austrian IBD patients are given in Table 1. Very good or excellent quality of life was reported by 97/224 (43.3%) CD patients and 69/140 (49.2%) UC patients. 77/240 CD patients (32%) and 58/135 UC patients (43%) were in clinical PRO-2 as well as biomarker remission and had a very good or excellent quality or life. Conclusion While a large number of IBD patients in tertiary university centers were in clinical PRO-2 remission a lower number of patients had a very good or excellent quality of life. Biomarker remission was achieved almost equally often as clinical PRO-2 remission in UC patients but less often in CD patients. About one third of the patients were in clinical PRO-2 and biomarker remission and had a very good or excellent quality of life. Despite the frequent use of advanced therapies there is a need for treatment optimizing to reach all treatment goals.

P1036 The PODIUM Study: A three-arm comparison of target therapies after anti-TNFα in ulcerative colitis – an interim analysis

Abstract Background Anti-tumor necrosis factor(TNF)α are the first target therapies approved to treat ulcerative colitis(UC). Drugs with different mechanisms of action(MoA) have then entered the market, but data on the optimal management of UC after failure of 1-line anti-TNFα are lacking. Methods The PODIUM study is a retrospective, observational study comparing the real-life effectiveness and safety of 2-line vedolizumab(VDZ), ustekinumab (UST) and JAK inhibitors(JAKi). Consecutive UC patients(pts) failure to 1+ anti-TNFα and never exposed to other MoA were enrolled from 13 European centres. Sociodemographic data, data on clinical activity and adverse events of interest(AEIs) were collected, from the initiation of 2-line therapy until 1 year of observation/drug discontinuation/last follow-up. The primary outcome was steroid-free clinical remission(SFCR); inverse probability of treatment weighting(IPTW) was applied to all outcomes. This interim analysis includes data collected up to August 2024; data collection is still ongoing. Results Data on 352 patients (187VDZ, 76UST, 89JAKi) were included. Baseline characteristics are presented in Table1. After IPTW, the cumulative probability of achieving SFCR during the first year was 52%, 68% and 71% for VDZ, UST and JAKi, respectively; both UST and JAKi were superior to VDZ at Log-rank test(p<0.05), with no differences between the two (Figure1). Stool frequency scores were significantly lower at 12 months in the UST- and JAKi-groups, compared to the VDZ-group(0.5 and 0.5 vs 1.2, p<0.05 for both); rectal bleeding scores were nearly significantly lower at 12 months in the UST- and JAKi-groups, compared to the VDZ-group(0.2 and 0.2 vs 0.6, p<0.05 for both). Recorded AEIs were 10(5.3% of VDZ pts, 4 infections) in the VDZ group, 7(9.2% of UST pts, 1 infection) in the UST group, 17(19.1% of JAKi pts, 10 infections including 1 Zoster reactivation) in the JAKi group. Conclusion This preliminary analysis suggests that both UST and JAKi might have superior effectiveness, compared to VDZ, as second-line agents in patients with UC, after anti-TNF-α. A significantly higher rate of AEIs was observed in the TOF group. Confirmatory analysis with a larger sample size will be performed.

DOP004 Proactive fecal calprotectin testing in ulcerative colitis: Initial results of the PROMOTE UC study

Abstract Background Fecal calprotectin (FC) is a biomarker of mucosal inflammation widely used in the management of inflammatory bowel disease (IBD). Given the convenience of home-based FC testing, we hypothesized that intensive, proactive FC monitoring would prevent symptomatic ulcerative colitis (UC) flares by detecting elevated FC levels prior to symptom onset and allowing clinicians to optimize therapy. Methods This prospective, multicenter, randomized, observational clinical trial evaluated intensive home-based, FC testing (IBDoc, Bühlmann Laboratories) versus usual care in adults with UC in clinical remission, defined as a modified partial Mayo score (mpMayo) ≤2 with no rectal bleeding. Patients in the intervention arm used the home testing kit every 2 months for 18 months or until symptomatic flare. The decision to modify therapy based on an elevated FC result was left to the discretion of the attending physician. Patients in the control group were followed according to usual care for 18 months or until symptomatic flare. Clinical data were collected at baseline and every 6 months. The primary endpoint was the time to symptomatic flare, defined as an increase in mpMayo ≥2 points from baseline or a rectal bleeding score ≥1. Results A total of 584 patients were followed at 14 sites in Canada and Australia until symptomatic flare or end of study. Demographics were similar between the control (n=293) and intervention arms (n=291), including mean age (41.9 vs 41.9 years), sex (46.8% vs 49.1% male), disease duration (1.61 vs 1.44 years), and mean mpMayo (0.39 vs 0.40) (Table). At study end, the flare rate of 30.9% in the intervention arm with proactive monitoring was slightly lower than the flare rate of 32.8% in the control arm (median follow-up 549 and 562 days, respectively). Overall, HR for flare in the intervention vs control arm was 1.01 (95% CI: 0.76, 1.34; p=0.96) (Figure). Risk for flare was also similar when analyzed by disease extent (proctitis: 1.13 [0.60, 2.14, p=0.71]; left-sided disease: 0.99 [0.61, 1.58, p=0.95]; pancolitis: 0.96 [0.60, 1.53, p=0.86]) or biologic use (biologics: 1.29 [0.86, 1.95, p=0.22], non-biologics: 0.78 [0.52, 1.18, p=0.24]) at baseline. Conclusion In this large, prospective clinical trial, approximately one-third of patients with UC in clinical remission developed a symptomatic flare within 18 months. Longitudinal proactive FC monitoring was not associated with a reduction in clinical flares. Further study is needed to determine the utility of home-based FC testing in guiding the management of UC.

P0878 Early lymphocytosis is a novel predictor of response to rescue infliximab in acute severe ulcerative colitis: results from PREDICT-UC

Abstract Background The ability to predict failure of infliximab (IFX) in acute severe ulcerative colitis (ASUC) is crucial to identify patients who may benefit from dose-escalation, sequential rescue or early colectomy. Methods PREDICT-UC (NCT02770040) was a randomised controlled trial that compared IFX dosing strategies in ASUC.1 Clinical factors and biomarkers were collected daily between day 0 to 3 post-IFX and assessed on their ability to predict IFX failure (Lichtiger score ≥10 on day 14) and 3-month colectomy. Stepwise logistic regression was used to develop a Risk of IFX Failure (RIF) index, which was calibrated against the observed risk of IFX failure. The RIF index represents the predicted probability of IFX failure and takes on values between 0 and 1. Internal validation was performed using bootstrap validation. Results Of 138 patients, 46 received a first IFX dose of 10mg/kg and 92 received 5mg/kg; 39 (28%) experienced IFX failure and 17 (12%) required colectomy by 3 months. There was no difference in lymphocyte count (LC, ×109/L) on day 0 (prior to IFX) in patients who failed or responded to IFX (median [IQR] 1.1 [0.9–1.6] vs 1.3 [0.9–1.8], P=0.47). LC rose by day 3 in both groups, though to a lesser degree in patients who failed IFX (median [IQR] 1.9 [1.4–2.8]) compared to responders (3.3 [2.1–4.9]; P=0.004), and lower in patients requiring colectomy (median [IQR] 1.4 [1.1–1.9] vs 3.0 [2.0–4.8]; P<0.001). A lower day 3 LC was predictive of IFX failure (AUC 0.71, 95% CI 0.60–0.81) and colectomy (AUC 0.83, 95% CI 0.74–0.92). A higher CRP was predictive of both IFX failure and colectomy at all time-points from days 0 to 3 (day 3 CRP AUC 0.68, P=0.003 and 0.70, P=0.019 respectively). A lower day 3 albumin predicted IFX failure (AUC 0.63, P=0.039) while a lower day 2 albumin predicted colectomy (AUC 0.66, P=0.042). The final RIF index comprised day 3 stool frequency, rectal bleeding score, CRP and LC. The RIF index had a naïve AUC of 0.80 and an optimism-adjusted AUC of 0.73 (95% CI 0.65–0.80) for predicting IFX failure, and a naïve AUC of 0.90 and an optimism-adjusted AUC of 0.88 (95% CI 0.81–0.94) for predicting colectomy. A RIF index threshold of ≥0.15 had an 85% sensitivity and 90% negative predictive value (NPV) for IFX failure and a 94% sensitivity and 98% NPV for colectomy, while a threshold of ≥0.50 had a 92% specificity and 69% positive predictive value (PPV) for IFX failure, and an 88% specificity and 42% PPV for colectomy. Conclusion Lymphocytosis by day 3 is a novel predictor of response to IFX rescue in ASUC. The RIF index is a simple on-treatment risk index that predicts IFX failure and colectomy, and may be used to inform IFX dose-optimisation or switch to alternate therapies. References 1Choy MC, Li Wai Suen CFD, Con D, et al. Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial. Lancet Gastroenterol Hepatol 2024; 9(11): 981-96.

P1000 A quasi-experimental study evaluating effectiveness of partial enteral nutrition combined with exclusion diet in patients with mild to moderately severe ulcerative colitis

Abstract Background We designed this trial to evaluate efficacy of partial enteral nutrition (PEN) combined with exclusion diet (ED) in patients with mild to moderately active ulcerative colitis (UC). Methods In this quasi-experimental study, patients with mild-to-moderate UC (SCCAI=3-11) were allowed to choose either PEN+ED along with standard of care (SOC) or SOC alone. Disease activity was measured using simple clinical colitis activity index (SCCAI). Primary outcome was clinical remission (SCCAI≤2) 4 weeks. In addition, fecal microbiota analysis was performed at baseline and after week 4 in ten responders and four non-responders in PEN+ED arm. Results Sixty UC patients were included (PEN+ED=30; SOC=30). In the intervention group, 23 patients completed 4 weeks of PEN, 3 took a lower than prescribed dose, and 4 stopped after one week but continued ED. At week 4, 66.7% (20/30) patients in the PEN+ED arm achieved clinical remission at week 4 compared to 83.3% (25/30) receiving SOC. The proportion of patients with stool frequency score≤1 was similar between the two arms (90% vs 93.3%, p>0.99), however proportion of patients with rectal bleeding score ‘0’ was lower in patients receiving PEN+ED (56.7% vs 86.7%, p=0.01) at week 4. A numerically higher number of patients required steroids in SOC arm compared to PEN+ED arm, but it was not significant (23.3% vs 16.7%, p=0.748). At the microbiome level, PEN+ED was associated with a significant enrichment of ‘healthy-gut’ associated taxa (Figure 1) at week 4 compared to baseline and a concomitant-significant reduction in median Kendall distance to reference healthy Indian controls (p-value ≤1e-5), indicating the treatment shifts the microbiomes of patients towards controls. Conclusion Although PEN+ED does not appear to have additional clinical benefit to SOC at week 4, it was associated with significant improvement in gut microbiota. Long-term benefits of this therapy should be explored in future trials. Table 1: Baseline characteristics of included patients Figure 1: Figure showing change in the composition of the top 20 taxa across baseline and week4 with parenteral nutrition and exclusion diet in ulcerative colitis patients

P1085 Early and sustained improvement in patient-reported outcomes and biomarker concentrations with tulisokibart induction in patients with moderately to severely active ulcerative colitis: A post-hoc analysis from ARTEMIS-UC

Abstract Background In the phase 2, double-blind, placebo-controlled, multicenter ARTEMIS-UC trial, 12 weeks of induction treatment with the anti-tumor necrosis factor-like cytokine 1A (TL1A) monoclonal antibody tulisokibart led to significant rates of clinical remission, endoscopic improvement and mucosal healing, and improvement in patient-reported outcome (PRO) measures and disease surrogate biomarkers in patients with moderately to severely active ulcerative colitis (UC).1 This post-hoc analysis from ARTEMIS-UC examined the time course of improvement from baseline in patient-reported symptoms (PRO-2 score [combined Mayo stool frequency and rectal bleeding subscores]) and biomarkers (fecal calprotectin and high-sensitivity C-reactive protein [hs-CRP]) with tulisokibart. Methods Adults with moderately to severely active UC were randomized 1:1 to receive i.v. placebo or tulisokibart (1000 mg on Day 1 and 500 mg at Weeks 2, 6, and 10). The study population consisted of 2 cohorts based on a genetic diagnostic test (Dx) assessing likelihood for responding to anti-TL1A treatment. Cohort 1 included participants stratified by Dx results while Cohort 2 included only Dx positive participants. Cohort 1 is the population used in this post-hoc analysis. Participants recorded stool frequency and rectal bleeding scores daily using an e-diary. Fecal calprotectin was assessed at baseline and Weeks 6 and 12, and hs-CRP was assessed at baseline and Weeks 2, 6, 10, and 12. Symptomatic response was defined as a reduction from baseline in PRO-2 score ≥ 1 point. A mixed model repeated measures approach was used to compare tulikisobart to placebo for the difference in PRO-2 score for the first 14 days of treatment and the fold change from baseline in fecal calprotectin and hs-CRP at each timepoint. Results Among 135 randomized participants in Cohort 1, 60/67 (89.6%) receiving placebo and 68/68 (100%) receiving tulisokibart completed the 12-week induction period. The numerical difference in improvement of PRO-2 started as early as Day 2 and achieved significant improvement with tulisokibart compared to placebo at Day 9, with a sustained improvement persisting from the latter part of Week 2 through Week 12 (Figure 1, Table 1). Significant improvements with tulikisobart compared to placebo in fecal calprotectin and hs-CRP were observed by Weeks 6 and 2 (the first time point when these biomarkers were measured), respectively, which were maintained through Week 12 (Table 1). Conclusion In patients with moderately to severely active UC, induction with tulisokibart led to early and sustained improvement in patient-reported outcomes. Induction with tulisokibart also led to early and persistent improvement in biomarkers.

Three-Year Efficacy and Safety of Mirikizumab Following 152 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study.

Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, has demonstrated induction of clinical remission at week 12 with maintenance through week 104 in patients with moderately-to-severely active ulcerative colitis (UC). Results are presented from the LUCENT-3 open-label extension study through week 152. Of 868 LUCENT clinical trial program mirikizumab-treated induction patients, 544 were responders of whom 365 were rerandomized to mirikizumab maintenance. Of these, 324 completed week 52 and 316 entered extension treatment (286 week 52 responders; 179 week 52 remitters). Efficacy and safety outcomes are reported for mirikizumab-treated LUCENT-3 participants, including biologic-failed patients, with data for week 52 maintenance responders/remitters. Discontinuations or missing data were handled by nonresponder imputation, modified nonresponder imputation (mNRI), and observed cases. Using mNRI, 81.6% of week 52 responders demonstrated clinical response at week 152. Week 152 remission rates for week 52 responders included clinical (56.1%), corticosteroid-free (CSF; 54.5%), endoscopic (61.0%), histologic-endoscopic mucosal remission (HEMR; 52.6%), symptomatic (74.9%), and bowel urgency (BU; 58.6%). At week 152, 53.3% of week 52 responders achieved histologic-endoscopic mucosal improvement (HEMI) and 74.3% achieved BU clinically meaningful improvement (CMI). Among week 52 remitters, 85.4% showed a clinical response at week 152, with clinical (70.1%), CSF (68.9%), endoscopic (72.0%), HEMR (63.4%), symptomatic (81.4%), and BU (60.8%) remission. At week 152, among week 52 remitters, 64.0% of patients achieved HEMI and 75.6% achieved BU CMI. Stool frequency, rectal bleeding, BU, and abdominal pain score reductions from induction baseline to maintenance week 52 were sustained through week 152 for week 52 completers. Overall, in the safety population, 7.4% of patients reported severe adverse events (AEs); 5.3% discontinued treatment due to AEs. AEs of special interest included opportunistic infection (1.8%), hepatic disorders (3.2%), cerebrocardiovascular events (1.5%), and malignancy (0.3%). Patients with antidrug antibodies reduced over time from 23.6% in year 1 to 3.2% in year 3. Symptomatic, clinical, endoscopic, histologic, and quality-of-life outcomes support long-term sustained benefit of mirikizumab treatment up to 152 weeks in patients with UC, including biologic-failed patients, with no new safety concerns. ClinicalTrials.gov: NCT03518086; NCT03524092; NCT03519945.

Treatment of active ulcerative colitis with Yinmei Kuijie decoction combined with 5-aminosalicylic acid: A non-randomized multicenter prospective observational protocol based on real-world conditions

ObjectiveTo determine the efficacy and safety of the Yinmei Kuijie decoction combined with 5-aminosalicylic acid (5-ASA) in treating mildly to moderately active ulcerative colitis (UC) under real-world conditions. MethodsThis multicenter, prospective, non-randomized, observational study will be conducted in real-world settings. A total of 204 eligible patients will be consecutively enrolled in the study. Patients in the combination treatment group will receive Yinmei Kuijie decoction in combination with 5-ASA, whereas those in the control group will be treated with 5-ASA alone. The primary endpoint will be a clinical response at week 12, defined as a ≥3 point and ≥30% reduction from baseline in the Mayo total score with ≥1 reduction in rectal bleeding or rectal bleeding score = 0 or 1. Secondary efficacy endpoints at week 12 will include health-related quality of life, mucosal healing, and inflammation indicators. ConclusionThe results of this study may provide evidence of the efficacy and safety of Yinmei Kuijie decoction combined with 5-ASA in treating patients with mildly to moderately active UC under real-world principles. The results will provide a basis for further confirmatory studies on the efficacy of Yinmei Kuijie decoction.

Risankizumab for Ulcerative Colitis

The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups. Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135.

Differential efficacy of medical therapies for ulcerative colitis according to disease extent: patient-level analysis from multiple randomized controlled trials

Disease extent in Ulcerative Colitis (UC) has prognostic implications for disease course. It is unclear whether the efficacy of medical therapies for moderate to severely active UC vary according to disease extent at enrollment. We analyzed patient level data from 11 Phase 2 and 3 clinical trials of advanced therapies in patients with moderate-to-severe UC to assess modifications of advanced therapy effects by disease extent. Primary outcome was clinical response and secondary outcomes were clinical remission, endoscopic response/remission and endoscopic improvement, and Mayo clinic subscore for both induction and maintenance studies. Binary and continuous outcomes were analyzed using the modified Poisson regression model and the mixed-effects model, respectively, adjusting for age, sex, disease duration, concomitant steroid use and prior anti-TNF use. Effect modifications with binary outcomes were quantified by ratios of risk ratio for left-sided to that for extensive colitis while effect modifications with the Mayo subscores were quantified by differences of the differences between mean scores of the left-sided and extensive colitis. Results were presented with point estimates and 95% confidence intervals as well as p-values. Eleven clinical trials enrolling 5450 UC patients (infliximab=2, adalimumab=2, golimumab=2, vedolizumab=2, tofacitinib=3) were included. In induction trials, there was evidence to suggest effect modification by disease extent for clinical response with tofacitinib (the ratio of RRs 0.67, 95% CI [0.45, 0.99], p=0.049) and clinical remission with infliximab (ratio of RRs 0.33, 95% CI [0.13, 0.85], p=0.020) favoring patients with extensive colitis. There was no evidence to suggest effect modification for endoscopic improvement and clinical outcomes. There was evidence to suggest effect modification by disease extent for clinical remission with tofacitinib (ratio of RRs 0.44, 95% CI [0.22, 0.89], p=0.020) favoring patients with extensive colitis. For symptom subscores from the Mayo Clinic score, tofacitinib was associated with a greater reduction in both stool frequency (difference of differences 0.37, 95% CI [0.08, 0.65], p=0.012) and rectal bleeding scores (difference of differences 0.25, 95% CI [0.03, 0.47], p=0.026) in patients with extensive colitis compared to left sided. These findings underscore the possibility of differential efficacy of medical therapies according to disease distribution. These results warrant further exploration in forthcoming trials to better inform treatment strategies and consideration of disease distribution as a baseline stratification factor in clinical trials. This study did not receive any financial support.

Intrarectal formalin treatment for haemorrhagic radiation-induced proctopathy: efficacy and safety.

Pelvic radiotherapy is limited by dose-dependent toxicity to surrounding organs. The aim of this prospective study was to evaluate the efficacy and safety of intrarectal formalin treatment for radiotherapy-induced haemorrhagic proctopathy (RHP) at the Royal Marsden Hospital. Adult patients were enrolled. Haemoglobin was evaluated before and after formalin treatment. Antiplatelet and/or anticoagulation treatment and administration of transfusion were recorded. The interval between completion of radiotherapy and the first intrarectal 5% formalin treatment was assessed and the dose of radiotherapy was evaluated. Clinical assessment of the frequency and amount of rectal bleeding (rectal bleeding score 1-6) and endoscopic appearance (grade 0-3) were classified. Complications were recorded. Nineteen patients were enrolled, comprising 13 men (68%) and 6 women. The mean age was 75 ± 9 years. The median time between completion of radiotherapy and the first treatment was 20 months [interquartile range (IQR) 15 months] and the median dose of radiotherapy was 68 Gy (IQR 14 Gy). Thirty-two procedures were performed (average 1.7 per patient). In total, 9/19 (47%) patients were receiving anticoagulation and/or antiplatelet medication and 5/19 (26%) received transfusion prior to treatment. The mean value of serum haemoglobin before the first treatment was 110 ± 18 g/L and afterwards it was 123 ± 16 g/L (p = 0.022). The median rectal bleeding score before the first treatment was 6 (IQR 0) and afterwards 2 (IQR 1-4; p < 0.001), while the median endoscopy score on the day of first treatment was 3 (IQR 0) compared with 1 (IQR 1-2) on the day of the last treatment 1 (p < 0.001). One female patient with a persistent rectal ulcer that eventually healed (18 months of healing) subsequently developed rectovaginal fistula (complication rate 1/19, 5%). Treatment with intrarectal formalin in RHP is effective and safe.

Efficacy and safety of filgotinib for ulcerative colitis: A real-world multicenter retrospective study in Japan.

While filgotinib, an oral Janus kinase (JAK) 1 preferential inhibitor, is approved for moderately to severely active ulcerative colitis (UC), real-world studies assessing its short- and long-term efficacy and safety are limited. This is a multicenter, retrospective study of UC patients who started filgotinib between March 2022 and September 2023. The primary outcome was clinical remission, defined as a partial Mayo score ≤1 with a rectal bleeding score of 0, or Simple Clinical Colitis Activity Index (SCCAI) ≤2 with a blood-in-stool score of 0. Secondary outcomes included clinical response, corticosteroid-free remission, and endoscopic improvement. Outcomes were assessed at 10, 26, and 58 weeks based on patients with available follow-up. Adverse events were evaluated. We identified 238 UC patients and 54% had prior exposure to biologics/JAK inhibitors. The median baseline partial Mayo score and SCCAI were 5 (IQR 3-6) and 4 (IQR 2-7). Clinical remission rates based on per-protocol analysis at 10, 26, and 58 weeks were 47% (70/149), 55.8% (48/86), and 64.6% (31/48), respectively. At a median follow-up of 28 weeks (IQR 10-54) with a discontinuation rate of 39%, the rates of clinical remission, clinical response, corticosteroid-free remission, and endoscopic improvement were 39.9% (81/203), 54.7% (111/203), and 36.5% (74/203), and 43.5% (10/23), respectively. These rates were comparable between biologic/JAK inhibitor-naïve and -experienced patients. While three patients (1.3%) developed herpes zoster infection, no cases of thrombosis or death were reported. Real-world data demonstrate favourable clinical and safety outcomes of filgotinib for UC.

P687 Ozanimod as a once-daily oral therapy for Japanese patients with ulcerative colitis: results from the induction period of a Phase 2/3 study (J-True North)

Abstract Background Ozanimod is an oral, small molecule sphingosine 1-phosphate (S1P) receptor modulator that selectively targets the S1P1 and S1P5 receptor subtypes. Ozanimod is approved in multiple countries outside Japan for the treatment of moderately to severely active ulcerative colitis (UC) and/or relapsing forms of multiple sclerosis. We herein report the efficacy and safety results during the induction period of J-True North, a multi-centre, randomised, double-blind, placebo-controlled clinical Phase 2/3 study consisting of a 12-week induction period, followed by a 40-week maintenance period and an open-label extension period in Japanese patients with moderately to severely active UC. Methods Japanese male and female UC patients aged 18 to 75 years with moderately to severely active UC (defined as Mayo score of 6 to 12, with endoscopic subscore ≥2, rectal bleeding score (RBS) ≥1, and stool frequency score ≥1) were randomised in a 1:1:1 ratio to receive either 0.46 mg or 0.92 mg ozanimod, or placebo capsules orally once daily. All patients had received prior treatment with aminosalicylates or corticosteroids. The primary endpoint was clinical response at Week 12 (defined as a reduction from baseline in the complete Mayo score of ≥ 3 points and ≥ 30%, and a reduction from baseline in the RBS of ≥ 1 point or an absolute RBS of ≤ 1 point), and key secondary endpoints were clinical remission, clinical response, endoscopic improvement, mucosal healing and safety at Week 12 and 52. Results Patients were randomised to the ozanimod 0.46 mg group (n=68), 0.92 mg group (n=65), and the placebo group (n=65). At baseline, 36.4% of patients were female, mean age was 42.6 y and mean complete Mayo score was 8.4. The clinical response rate at Week 12 was 52.9%, 61.5%, and 32.3% in the ozanimod 0.46 mg, 0.92 mg, and placebo groups, respectively, demonstrating a statistically significant improvement of ozanimod vs placebo (Figure 1). Similarly, higher improvement rates were observed in all key secondary clinical and endoscopic endpoints in the ozanimod groups compared with the placebo group at Week 12. Frequent adverse events (AEs) observed in the induction period were nasopharyngitis, headache, et.al. (Table 1). AEs observed in the study were similar to those in the global phase 3 True North study with 0.92 mg ozanimod, and there were no new safety signals with ozanimod in the J-True North study. Conclusion Ozanimod as a once-daily oral therapy was effective as induction therapy for Japanese patients with moderately to severely active UC, and the safety profile was consistent with the results of previous studies. Figure 1 Table 1

P413 Bowel Urgency in patients with Ulcerative Colitis: prevalence and association with clinical, endoscopic data and disability

Abstract Background Bowel urgency (BU), identified as the sudden need for bowel movements, is increasingly being recognized as an impactful symptom in patients with ulcerative colitis (UC), distinct from stool frequency (SF) and rectal bleeding (RB). We aimed to assess the association of BU with patient-reported outcomes (PRO), including SF and RB, as well as clinical and endoscopic activity and disability in a real-world setting, using data from the IBD-Disk:Italian translation and validation study. Methods We conducted a cross-sectional multicentre study, consecutively including ≥ 18yo UC patients between February 2023 and October 2023. Demographic, clinical and endoscopic data were collected. Clinical remission was defined as partial Mayo score ≤ 1 and endoscopic activity as MES ≥ 1. All patients completed the following questionnaire for disability IBD-Disk and IBD Questionnaire-32 (IBDQ-32) for quality of life. BU was assessed using the question about regulating defecation in the past 7 days using a 10-point NRS ranging from 0 (absolutely disagree) to 10 (totally agree) from the IBD-DISK. RB was measured from question 22 of IBDQ and SF from question 1 of IBDQ-32, both using a 7-point NRS ranging from 0 (always) to 7 (never). Results 209 UC patients with a median age of 37(IQR 28-52) were enrolled, 111(53.1%) being female. Overall, 31 (14.8%) had proctitis, 91(45.5%) had left colitis and 87(41.6%) had extended/pancolitis. The median pMAYO score was 4(IQR=2-6), while the median MES was 2(IQR=1-2). 75% patients (35.9%) reporting BU were more likely to have moderate clinical (pMAYO=5; IQR=3-6) and endoscopic activity of disease (median MES=2; IQR=1-2) compared to those without urgency (p&amp;lt; .0001). Additionally, BU was associated with a higher median rate of hospitalizations in the previous 12 months (Δ=1; p&amp;lt;0.001).Patients with BU reported a higher degree of RB(33.3%) and SF(50,7%) than patients without BU (p&amp;lt; .0001).Noteworthy, individuals with BU had higher median IBD-DISK total score (29; IQR=9-52) and lower scores for IBDQ-32 (168;IQR=138-196) compared to patients without BU [median IBD-DISK=17(IQR=5-39); median IBDQ-32=181,IQR=158-202), p&amp;lt;0.001]. In the univariate analysis, BU was associated with a higher IBD-DISK total score (OR=1.04,CI=1.02-1.06; p&amp;lt;0.001) and SF (OR=0.59,CI=0.45-0.78; p=0.001), without being associated with RB (p=0.57) and IBD-Q32 total score (p=0.84). Conclusion BU can be a surrogate marker for UC clinical and endoscopic activity. Our findings suggest that it is an independent factor from RB and it is associated with disability. Hence, it can be considered as an additional key PRO in UC. However, a systematic standardized approach for BU definition and assessment is strongly awaited to incorporate it as treat-to-target measure