Bowel Urgency Research Articles

REAL-WORLD EFFECTIVENESS OF USTEKINUMAB IN PATIENTS WITH ULCERATIVE COLITIS IN THE UNITED STATES OF AMERICA

Abstract BACKGROUND Primary treatment goals for ulcerative colitis (UC) are to induce and maintain long-term disease remission and reduce the prevalence of symptoms such as bowel urgency and abdominal pain. Ustekinumab (UST) is a biologic approved for treating adult patients with moderate-severe UC, but real-world effectiveness data remain limited. OBJECTIVE We aimed to assess real-world effectiveness of UST in patients with UC. METHODS Data were drawn from the Adelphi Real World UC Disease Specific Programme™, a cross-sectional survey with retrospective data collection of gastroenterologists and their patients in the United States of America (USA) from December 2022–September 2023. Two samples were utilised; a sample where physicians provided data for their next six consecutive patients with UC, and an oversample where physicians provided data for their next four consulting patients with UC receiving UST. Patients receiving UST for >1 day at time of consultation (assumed to have received ≥1 UST dose) from either sample were included in the analysis. Data collected included clinical status, disease duration and location, symptoms and treatment profiles. Remission defined by Mayo score was reported separately for advanced therapy (AT)-naïve (UST received as first AT) and AT-experienced (UST received as second or later line of AT) patients. Descriptive statistics for each variable were reported for patients with known data. McNemar’s test was used for symptom prevalence and disease severity comparisons. RESULTS Data for 160 patients were included in this study from 50 physicians. Patients had been diagnosed with UC for median (interquartile range; IQR) of 2.2 (0.5, 4.5) years; mean (standard deviation) age was 39.7 (13.0) years and 50.0% of patients were male. UST was received as first AT for 68.1% of patients, second AT for 18.1% and third AT for 11.3%. Median (IQR) time on UST was 8.7 (4.1, 18.6) months, with 83.9% of patients receiving UST for ≥3 months. For patients in maintenance phase of treatment, 65.8% were on UST USA label dose, 17.9% were receiving an increased and 16.3% decreased dose. According to Mayo scores, 53.6% of AT-naïve and 58.3% of AT-experienced patients were in remission at consultation (Table 1). Improvement in disease severity was evidenced by a reduced proportion of patients with moderate/severe disease at consultation (34.4%) compared to prior to initiation of UST (90.9%; p<0.01). Similarly, there was a significantly lower prevalence of all symptoms between UST initiation and consultation, including abdominal pain (72.1% vs 30.2%), bowel urgency (55.1% vs 22.0%) and bloody diarrhea (54.4% vs 17.6%) (all p<0.01; Figure 1). CONCLUSION Our study showed real-world effectiveness of UST in patients with UC in the USA; most patients receiving UST achieved remission and demonstrated reduced prevalence of symptoms following UST initiation. Table 1 Physician-reported characteristics of patients receiving ustekinumab at the time of consultation. Figure 1 Physician-reported prevalence of (A) symptoms and (B) moderate/severe disease severity prior to initiation of ustekinumab and at time of consultation.

REAL-WORLD EXPERIENCE AND PERSPECTIVES ON THE TREATMENT OF ULCERATIVE COLITIS: RESULTS FROM A HEALTHCARE PROVIDER SURVEY

Abstract BACKGROUND Treatment decisions for patients with ulcerative colitis (UC) depend on the disease severity. This observational, cross-sectional, web-based survey sought to provide insight into the real-world symptoms and clinical characteristics that factor into healthcare providers’ (HCPs) treatment choices for their patients with UC in the United States. METHODS Self-reported data were collected from HCPs using a standard web-based questionnaire between 21 November 2022 and 6 December 2022. Eligible HCPs were required to have treated at least 10 adult patients with UC per month, worked more than 20 hours per week in direct patient care; and be able to complete the survey in English. HCPs included gastroenterologists (GIs), primary care physicians (PCPs), internal medicine (IM) or family medicine (FM) physicians, nurse practitioners (NPs), or physician assistants (PAs). Questionnaire responses were summarized through descriptive statistics, and post hoc comparisons between HCP types (GIs, FM/IM/PCPs, PAs, NPs) were performed using binomial regression models without adjustment for multiple comparisons. RESULTS Among 459 HCPs (male: 47.9%; 30-49 years age-group: 55.1%), 55.3% were physicians, 22.7% were NPs, and 22.0% were PAs. Approximately, 50% of the HCPs described their primary medical specialty as primary care/family care, followed by 37.7% in gastroenterology, and 12.9% in IM. From a list of 13 symptoms, when asked to select three symptoms they considered most important in deciding a course of treatment for UC, HCPs chose rectal bleeding (60%), followed by cramping or other abdominal pain (45%), diarrhea (41%), anemia (34%), and bowel urgency (28%, Fig. 1). The proportions were similar across HCP types except a greater proportion of GIs (60%) selected diarrhea than the other specialties (NPs: 42%, P=0.0127; FM/IM/PCPs: 33%, P<0.0001; PAs: 32%, P<0.0001). Rectal bleeding (87.4%), clinical remission (86.7%), abdominal pain (81.4%), stool frequency (77.6%), bowel urgency (77.3%), mucosal appearance (72.9%), and histologic appearance (71.5%) were rated as “very important” or “extremely important” by HCPs for deciding treatment choices (Fig. 2). A higher percentage of GIs, PAs, and NPs rated several symptoms more frequently vs FM/IM/PCPs, including bowel urgency (GIs: P<0.0001; PAs: P=0.0182; NPs: P=0.0342), mucosal appearance (P<0.0001, P=0.0091; P=0.0009), and stool frequency (P=0.0013; P=0.0283; P=0.0114) as “very important” or “extremely important.” CONCLUSION Results suggest a need for education among some specialties, particularly FMs, IMs, and PCPs, about the clinical presentation of UC and most important symptoms to consider when deciding treatment options for patients with UC. Fig. 1 Most important ulcerative colitis symptoms healthcare providers selected when deciding on a patient’s course of treatment Fig. 2 The level of importance assigned by the healthcare providers to the symptoms when deciding on the course of treatment for the patients with ulcerative colitis

P415 The influence of bowel urgency on the quality of life in individuals with ulcerative colitis

Abstract Background Ulcerative colitis (UC) is a persistent inflammatory condition marked by periods of relapse and remission, significantly impacting overall quality of life (QoL). Among the various symptoms influencing this quality, bowel urgency (BU) stands out as particularly distressing. BU manifests with profound negative implications on physical health, psychological well-being, and social aspects. Furthermore, bowel urgency (BU) is often omitted from the majority of disease activity scoring systems and is not consistently considered as a treatment outcome. Our objective was to explore the impact of BU on specific subgroups of QoL measures and its correlation with the partial Mayo score. Methods During this cross-sectional study, patients were categorized based on both BU and the concurrent partial Mayo score. The patients completed the Whoqol Bref questionnaire for assessing their QoL. Long-term outcomes, such as steroid use, hospitalization and colectomy, were evaluated at the 6-month follow-up. Results The study included 154 patients diagnosed with UC. When comparing BU with the partial Mayo score in terms of QoL, significant differences were found in the physical health domain (p<0.001), psychology domain (p<0.001), social relationship domain (p<0.014), and environmental domain (p<0.001). Among patients in remission according to the partial Mayo score (25/117, 21.3%), a notable proportion experienced bowel urgency (BU). BU was identified as a predictor for both steroid requirement (OR: 4.7; 95% CI [2.3-9.7], p<0.001) and hospitalization (OR: 4.7; 95% CI [2.3-9.7], p<0.001) during the six-month follow-up period. None of the patients required surgical intervention. Notably, even among patients in remission according to the partial Mayo score (25/117, 21.3%), bowel urgency (BU) persisted. Conclusion We noted that the existence of BU significantly impairs the quality of life for individuals with UC. Moreover, it is associated with an increased probability of future steroid use and hospitalization. Notably, some patients still experienced BU even while in remission. Further investigations are necessary to elucidate the mechanisms contributing to the persistence of these symptoms in these individuals.

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

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

P349 Communicating Needs and Features of IBD Experiences (CONFIDE) Survey: Descriptive Comparison of Experiences of Bowel Urgency among Patients with Ulcerative Colitis in Canada, Europe, and the US

Abstract Background Bowel urgency is a disruptive symptom affecting daily lives of patients with moderate-to-severe ulcerative colitis (UC). Previous analyses from the Communicating Needs and Features of IBD Experiences (CONFIDE) survey reported bowel urgency as a common and impactful symptom of UC in the United States (US) and Europe. This study used data from the CONFIDE survey to descriptively compare the prevalence and impact of bowel urgency in patients with UC across US, Europe, and Canada. Methods Online, quantitative, cross-sectional surveys were conducted among patients with UC in the US, Europe (France, Germany, Italy, Spain, UK), Japan, and Canada. Criteria based on previous treatment, steroid use, and/or hospitalization defined moderate-to-severe UC. Descriptive comparisons of data from US, Europe, and Canada are presented. Results Surveys were completed by 82 Canadian, 556 European, and 200 US patients with UC. Across geographies, most patients were receiving advanced therapies at the time of survey completion (Canada:73%, Europe:54%, US: 77%; Table). Similar to the findings in Europe and US, bowel urgency was among the top three most common symptoms currently (in the last month) experienced by Canadian patients (Canada:31%, Europe:30%, US:47%; Figure 1a). Due to fear/anticipation of bowel urgency-related accidents, 60% Canadian patients reported wearing diaper/pad/other protection, at least once a month in the past 3 months, similar to European (65%) and US (69%) patients. Among Canadian patients who ever experienced bowel urgency (n=46, 56%), most (78%) reported doing so at least once a month in past 3 months with similar frequencies observed among US and European patients; proportion of patients experiencing bowel urgency at least once a week was higher among US (79%) and European (71%) patients than Canadian patients (48%) (Table). Among patients receiving advanced therapies, similar patterns were observed (Table). Most patients in all three populations reported bowel urgency and bowel urgency-related accidents among the top five most common reasons for declining participation in work/school, social events, and sports/physical exercise (Figure 1b). Conclusion These descriptive analyses suggest that although the overall prevalence and burden of bowel urgency in Canada are similar to those in the US and Europe, a numerically lower proportion of Canadian patients with moderate-to-severe UC experienced bowel urgency at least once a week in past 3 months. Despite receiving advanced therapies, patients experience bowel urgency and related diaper/protection use across geographies. These findings highlight the clinical importance of evaluating and treating bowel urgency to improve the quality of life of patients with UC across geographies.

P1010 Guselkumab improves abdominal pain and bowel urgency symptoms in patients with moderately to severely active ulcerative colitis: Results from the phase 3 QUASAR induction study

Abstract Background Abdominal pain and bowel urgency are prevalent, burdensome symptoms experienced by patients (pts) with ulcerative colitis (UC) that impact daily life, including social activities. In this study, we use data from the Phase 3 QUASAR Induction Study to assess efficacy of guselkumab (GUS) on abdominal pain, bowel urgency, and the impact of bowel urgency on pts’ lives. Methods Pts were randomized 3:2 to receive IV GUS 200mg or placebo (PBO) at Weeks (Wks) 0, 4, and 8. Abdominal pain and bowel urgency were evaluated at baseline and Wk12 using items from the Inflammatory Bowel Disease Questionnaire, where pts rated trouble with abdominal pain, symptoms of bowel urgency, and the impact of bowel urgency over the past 2 wks using 7-point scales (1=all of the time to 7=none of the time). A ≥2 point increase from baseline was clinically meaningful improvement. All analyses were prespecified but not multiplicity controlled; all p-values are nominal. Results At baseline, percentages of pts with abdominal pain (GUS 77.7% and PBO 77.9%), symptoms of bowel urgency (GUS 86.0% and PBO 83.2%), and impact of bowel urgency (GUS 70.8% and PBO 70.4%) at least a little of the time (score ≤5) were similar between groups. GUS-treated pts showed greater improvements at Wk12 in these outcomes compared with PBO (Table 1). For abdominal pain, 52.0% of GUS-treated pts had clinically meaningful improvements from baseline at Wk12 vs 33.0% in the PBO group (p<0.001), and 21.1% vs 12.3%, respectively, of those with abdominal pain at baseline had resolution at Wk12 (p=0.004; Fig. 1A). For symptoms of bowel urgency, 58.6% vs 33.0%, respectively, had clinically meaningful improvements (p<0.001; Fig. 1B), and 24.0% vs 9.8%, respectively, of those with symptoms of bowel urgency at baseline had resolution at Wk12 (p<0.001). Similarly, 57.7% vs 33.0%, respectively, had clinically meaningful improvements in the impact of bowel urgency (p<0.001; Fig. 1B), and 32.4% vs 13.1%, respectively, of those impacted at baseline had resolution at Wk12 (p<0.001). Symptoms and impact of bowel urgency were combined into a bowel urgency score; of pts with symptoms or impact scores ≤6 at baseline, 19.7% versus 8.2%, respectively, had resolution of both at Wk12 (p<0.001; Fig. 1B). Conclusion Pts receiving GUS showed clinically meaningful improvements in health-related quality of life measures related to abdominal pain and bowel urgency, including both the symptoms of bowel urgency and impact on pts’ lives.

P671 Patient perspectives on symptoms and impacts in Crohn’s disease: Results from qualitative research

Abstract Background Patients’ perspectives on their Crohn’s disease (CD) symptoms and the impacts of CD on their daily lives can be used to inform clinical care and treatment development. This study aimed to elicit in-depth qualitative information on the symptom burden of CD and to quantify which symptoms patients considered most bothersome and most important to improve. Methods Individual, web-based interviews were conducted in adults and adolescents (aged 15–17 years) with moderately to severely active CD. Participants were asked open-ended questions to elicit their experiences with CD and CD-related impacts on their daily lives. Participants were then probed about symptom- and impact-related concepts of interest that they did not spontaneously report. Participants were asked which symptoms they considered most bothersome and which symptoms they considered most important to improve. Interview transcripts and field notes were analyzed using a standard thematic analysis approach. Results 17 adults and 3 adolescents participated between May and July 2023. Participants were 17–60 [mean=38] years old; 70% were female [n=14]; 70% were White [n=14]. Participants had been diagnosed, on average, 10 (range: 0.5–29) years ago. Over half (n=13, 65%) reported moderate CD severity. Nearly all participants reported fatigue (n=19, 95%), bowel urgency (n=18, 90%), diarrhea (n=18, 90%), abdominal pain (n=17, 85%), and frequent bowel movements (n=15, 75%). About a third reported nausea (n=7, 35%), bloating (n=6, 30%), joint pain (n=6, 30%), or blood in their stool (n=6, 30%). In total, nine different most bothersome symptoms or treatment priorities were reported across participants (Figure 1). Participants most commonly reported abdominal pain (n=6, 30%), bowel urgency (n=4, 20%), and diarrhea (n=4, 20%) as their most bothersome symptoms; these were also the symptoms most commonly reported as the most important to improve (abdominal pain: n=7, 35%; bowel urgency: n=5, 25%; diarrhea: n=4, 20%) (Figure 1). All participants reported that CD hinders their daily activities, and nearly all reported that CD affects their mood or emotions (n=19, 95%), social activities or relationships (n=19, 95%), work or school (e.g., loss of productivity) (n=18, 90%), and sleep (n=15, 75%) (Table 1). Participants described "feel[ing] left out", "want[ing] to stay home", and having to cancel or leave activities because of their CD. Several participants indicated that they "plan their day around [their CD]". Conclusion Patients with moderately to severely active CD were burdened by a variety of symptoms. Patients commonly considered abdominal pain, bowel urgency, and diarrhea symptoms to be the most bothersome and the most important to improve.

P231 Impact of the depth of mucosal healing on the burden of ulcerative colitis : a cross-sectional study

Abstract Background Ulcerative colitis (UC) is a major cause of disability, affecting physical, emotional and social well-being. The recent STRIDE II international guidelines consider disability-free and normal quality of life as therapeutic targets. Today, the degree of mucosal healing required to reduce disability, incontinence and bowel urgencies is poorly known. Methods We conducted a single-center cross-sectional study between January 2021 and June 2023. All consecutive patients with UC and endoscopic healing (Mayo ≤ 1) underwent IBD-disk disability assessment the day of the colonoscopy. Histological healing was defined as Nancy score 0 or 1 (2 biopsies per segment from rectum to right colon). Moderate to severe disability was defined as an overall score ≥ 40. Incontinence was defined by a Wexner score >5 and bowel urgency by an NRS urgency score > 1). Results A total of 57 patients were included, with 34 (59.6%) women. Median age and disease duration were 47.4 (interquartile range [IQR] [43.5; 51.2]) and 13.0 years (IQR, 13.1-18.4), respectively. 37/57 (65%) patients had complete endoscopic healing Mayo 0 and 43/54 (80%) histological healing. The median overall IBD-Disk score was 29 [25.5; 37.5] and 27 (47%) had moderate to severe disability. There were no differences in terms of age, gender, body mass index, smoking status, disease extension and treatment for the 3 groups Mayo 1, Mayo 0 and histological healing. The rate of moderate to severe disability was not different among patients with Mayo 0 (7/20, 35%) vs. Mayo 1 (20/37, 54%) patients (p=0.26), or in patients with (22/43, 51%) or without histological healing (4/11,36%) (p =0.51). Of the 35 patients assessed, bowel urgency were reported in 11 (31.4%), with no difference between the two definitions of endoscopic healing (p=0.72) or histological healing (p=0.37). Among the 35 patients with a Wexner score evaluation, incontinence was observed in 19% (4/21) and 14% (2/14) of Mayo 0 and Mayo 1 patients respectively (p=0.99), and 24% (6/25) vs. 0% (0/7) of patients with or without histological healing (p=0.3). Conclusion Half of patients with UC who achieved endoscopic healing reported a moderate to severe disability. Mayo 0 (vs. 1) endoscopic healing and histological healing do not appear to provide any short-term benefit in terms of disability, fecal incontinence or bowel urgency.

P720 Exit interviews exploring Crohn’s disease patients’ experience of changes in their bowel urgency during the mirikizumab Phase 3 clinical trial in adult patients with moderate to severe Crohn disease

Abstract Background The objective of this study was to explore the clinical trial experience of patients with Crohn’s disease (CD), including perceptions of the Urgency Numeric Rating Scale (Urgency NRS) and meaningful within-patient change (MWPC). Methods Qualitative, 90-minute exit interviews were conducted with patients who had moderate to severe CD and completed the VIVID-1 phase 3, multicentre, randomized, double-blind, placebo and active-controlled, mirikizumab clinical trial in the past 3 weeks. The semi-structured interview guide included cognitive debriefing to explore the content validity of the 11-point Urgency NRS (0=No urgency to 10=Worst possible urgency in the past 24 hours). Interview transcripts were analysed using qualitative directed content analysis and framework analysis. Results Interviewed participants (N=62) were from the US (n=29), Czech Republic (n=10), Poland (n=8), Germany (n=7), Canada (n=4), Australia (n=3) and the UK (n=1). Participants (age 22–75 years, 55% female, 53% high school education or lower) were diagnosed with CD for 1–54 years. Most participants understood the Urgency NRS as assessing the severity of feeling an immediate need to go to the bathroom and used it accurately and without difficulty. Participants interpreted the Urgency NRS as ranging from “no urgency” [0] to an “immediate, sudden need or loss of bowel control” [10]. Participants reported that a ‘good day’ or ‘remission’ would feature reduced or no or minimal bowel urgency and permit adequate time to find a bathroom, feature no accidents and allow participation in daily/leisure/social activities and work away from home. Participants considered Urgency NRS scores ≤3 as a ‘good day’ (n=45/59) and ≤2 as ‘remission’ (n=41/57). Most reported that the bowel urgency improvement they experienced was meaningful (n=51/55; Table 1) because it improved their quality of life. A 3-point Urgency NRS improvement was identified as the smallest meaningful change (n=40/54; Table 1). Most participants associated bowel urgency with CD severity when responding to a Patient Global Rating of Severity (PGRS; n=42) and a Patient Global Impression of Change (PGIC; n=32). Most participants related Urgency NRS scores of 0 to None, 2 to Very Mild, 4 to Mild, 6 to Moderate, 8 to Severe and 10 to Very Severe on the PGRS (Figure 1). Urgency NRS improvements of 3-10 points were considered Much better or Very much better on the PGIC (Figure 1). Conclusion The Urgency NRS was well understood and a ≥3-point improvement in Urgency NRS score was considered a MWPC. Participants with CD who had completed the mirikizumab clinical trial perceived a meaningful change in bowel urgency to feature reduced or minimal bowel urgency enabling improved daily functioning.

OP12 Mirikizumab improves fatigue, bowel urgency, and quality of life in patients with moderately to severely active Crohn’s Disease: Results from a phase 3 clinical trial

Abstract Background Mirikizumab (miri), an anti-IL-23p19 antibody, is approved for the treatment of ulcerative colitis and under development for Crohn’s disease (CD). We investigated how miri impacted fatigue, bowel urgency, and health-related quality of life (HRQoL) through 52 weeks in patients with moderately to severely active CD in the Phase 3 VIVID-1 study. Methods In the treat-through VIVID-1 (NCT03926130) study, patients (N=1065) with moderately to severely active CD and a Simple Endoscopic Score for CD (SES-CD) score ≥7 (or ≥4 for patients with isolated ileal disease) and failure to biologic and/or conventional therapy were randomized in a 6:3:2 ratio to receive miri (N=579) (a single 900mg intravenous (IV) dose at W0, W4, and W8 followed by a subcutaneous (SC) dose of 300 mg at W12 and then every 4 weeks), ustekinumab (N=287) (6mg/kg IV at W0 and SC dose of 90mg at W8 and then every 8 weeks), or PBO (N=199). At W12 PBO responders continued PBO to W52; PBO-non-responders received the same blinded miri regimen as described above. This analysis focuses on results in patients randomized to either miri or PBO. The change from baseline for Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Urgency Numeric Rating Scale (UNRS), and Inflammatory Bowel Disease Questionnaire (IBDQ) total and domain scores (bowel symptoms, systemic symptoms, emotional function, social function) were analyzed through W52. IBDQ response (≥16-point improvement from baseline) and remission (total score ≥ 170) rates were also analyzed at W12 and W52. For binary variables, adjusted risk differences were compared between miri and PBO using the Cochran-Mantel-Haenszel (CMH) test. For continuous variables, least squares mean changes from baseline were compared between treatment groups using ANCOVA. Results Significant improvement in mean change from baseline to W12 and W52 were observed with miri for FACIT-F, UNRS, and IBDQ total and domain scores (all p<0.000001 at W52) (Figure 1&2). Miri-treated patients showed improved UNRS scores versus PBO as early as W8 with statistical significance sustained to W52 (Figure 1B). At W12 and W52, a greater percentage of miri-treated patients achieved IBDQ response (W12: p<0.000001; W52: p<0.000001) and remission (W12: p<0.000001; W52: p<0.000001) compared to PBO (Figure 2A&B). Conclusion Treatment with miri resulted in improvements in fatigue, bowel urgency, and HRQoL at W12 and W52 in patients with moderately to severely active CD.

P901 Extended induction response over time in patients with moderately-to-severely active Ulcerative Colitis treated with mirikizumab in the LUCENT-1 and -2 trials

Abstract Background The safety and efficacy of mirikizumab (miri), an anti-IL-23p19 antibody, for moderately-to-severely active ulcerative colitis (UC) have been shown in Phase 3 trials (LUCENT-1 and -2; NCT03518086, NCT03524092).1 Extended induction with 3 additional intravenous (IV) doses of miri induced clinical response at Week (W)24 in more than 50% of patients who did not initially achieve clinical response to induction with miri at W12.2 Among the clinical non-responders, some had achieved partial response at W12 (Table 1). We assessed response over time in clinical non-responders at the end of induction who received extended induction with miri for an additional 12W. Methods In LUCENT-1, patients (N=1281) were randomly assigned 3:1 to receive miri 300mg or placebo IV at W0, W4, and W8. Patients not achieving clinical response with miri 300mg IV at W12 of LUCENT-1 (n=272) received extended induction treatment with open-label miri 300mg IV at W12, W16, and W20 (LUCENT-2). Symptomatic remission, symptomatic response, bowel urgency (BU) remission, and BU change from baseline at W16 and W20 are reported (definitions in Table 1) in addition to the previously disclosed outcomes at W24. For categorical variables, number and percentage of patients who are responders/remitters were presented. For continuous variables, mean change from baseline with standard deviation (SD) was used. Missing data were imputed as non-response. Results Among patients who were clinical non-responders to 12W of initial induction treatment (n=272), 53 (19.5%); 73 (26.8%); 101 (37.1%) achieved symptomatic remission and 144 (52.9%); 169 (62.1%); 197 (72.4%) patients achieved symptomatic response at W16, W20, and W24, respectively. Among miri induction non-responders with Urgency Numeric Rating Scale (NRS) score ≥3 at induction baseline (n=256), 10.9% achieved BU remission at W16, 14.8% at W20, and 19.9% at W24. There was a 1.8±2.4 (mean±SD) point reduction in Urgency NRS scores at W16, 2.1±2.5 reduction at W20, and 2.5±2.7 reduction at W24 (Table 1). Conclusion Among patients who were clinical non-responders to induction at W12, more than 50% achieved clinical response after 3 additional induction doses with miri. A proportion of patients benefited earlier from extended induction at W16 and W20, respectively, regarding symptomatic response and remission, and BU outcomes. The results demonstrate continued symptomatic improvement and further support the potential benefit of extended induction treatment.

OP06 Risankizumab Maintenance Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Efficacy and Safety in the Randomised Phase 3 COMMAND Study

Abstract Background Risankizumab (RZB), a monoclonal antibody targeting interleukin-23 p19, was evaluated for maintenance therapy in patients with moderately to severely active ulcerative colitis (UC) and clinical response to RZB intravenous (IV) induction treatment in a phase 3 double-blind, placebo (PBO)-controlled withdrawal (WD) maintenance study, COMMAND (NCT03398135). Methods Patients with moderately to severely active UC who achieved a clinical response per Adapted Mayo score after 12 or 24 weeks (wks) of RZB IV treatment in the phase 2b and phase 3 INSPIRE induction studies (NCT03398148)1 were randomized 1:1:1 in COMMAND to RZB 180 mg (RZB180), 360 mg (RZB360), or PBO (RZB withdrawal) subcutaneous (SC) treatment every 8 wks for 52 wks. The efficacy analysis included responders to 12 wk of RZB IV, while the safety analysis included responders to 12 or 24 wk of RZB IV. The primary endpoint was clinical remission per Adapted Mayo score at wk 52. Key secondary endpoints included endoscopic improvement, HEMI, endoscopic remission, steroid-free clinical remission, maintenance of clinical remission, no bowel urgency, and no abdominal pain at wk 52. Results At baseline of induction, demographics and disease characteristics were similar between treatment groups; 75% of 548 patients had history of inadequate response or intolerance to ≥ 1 advanced therapy (AT). Patients receiving RZB180 (40.2%) and RZB360 (37.6%) achieved significantly higher rates of clinical remission vs WD (25.1%) (adjusted treatment difference vs WD: 16.3% and 14.2%, respectively; P ≤ .01) (Fig. 1A). Greater proportions of patients achieved endoscopic improvement, HEMI, endoscopic remission, steroid-free clinical remission, maintenance of clinical remission, no bowel urgency, and no abdominal pain with RZB180 and RZB360 vs WD (Fig. 1B). The overall rates of adverse events (AEs), and serious infections were similar among treatment groups (Table 1). Serious (presented as events/100 patient-years [E/100 PY]) (RZB180: 5.9; RZB360: 6.3; WD: 11.4) and severe AEs (RZB180: 1.6; RZB360: 4.0; WD: 8.0) were lower in the RZB arms vs WD. No active tuberculosis, adjudicated anaphylaxis, serious hypersensitivity, or adjudicated major adverse cardiovascular events were reported in any treatment group. Conclusion In patients with moderately to severely active UC responding to 12-week RZB induction therapy, RZB maintenance dosing with 180 mg and 360 mg SC was superior to placebo in achieving clinical remission as well as other key clinical, endoscopic, and histological-endoscopic endpoints. RZB was well-tolerated, with no new safety concerns observed.

P931 Burden of disease among Ulcerative Colitis patients with isolated proctitis in the United States and Europe

Abstract Background Isolated proctitis (IP), or ulcerative proctitis, a subtype of ulcerative colitis (UC), is associated with distressing symptoms such as abdominal pain and bowel urgency. As patients with IP not responding to conventional treatment are understudied and underrepresented in clinical trials, treatment guidance is limited. We aimed to understand disease burden among IP patients by describing patients delineated by disease extension and treatment experience. Methods Data were drawn from the Adelphi UC Disease Specific Programme™, a cross-sectional survey of gastroenterologists (GIs) and their consulting patients in France, Germany, Italy, Spain, the United Kingdom and the United States from October 2020 – March 2021. GIs reported patient demographics, disease extension, symptoms, components of the full Mayo score (allowing total scores to be calculated for patients), and treatment profile at time of consultation. Patients with a history of physician-assessed moderate-severe disease were included. Patients were categorised as IP (IP at diagnosis and consultation) or as more extensive UC (MEUC; where disease extended beyond IP at both diagnosis and consultation). According to ECCO consensus guidelines1, patients are considered refractory if they have failed oral steroids combined with oral and rectal 5-ASA therapy. In this analysis, non-refractory IP patients had only received 5-ASAs and/or steroids; refractory IP patients had received an immunomodulator (IM) and/or advanced therapy (AT; biologics, Janus kinase inhibitors). All analyses were descriptive. Results Overall, 221 IP patients (118 non-refractory, 103 refractory) and 1607 MEUC were analysed (Table 1). Among IP, non-refractory IP, refractory IP, and MEUC 49.3%, 55.1%, 42.7%, and 55.4% were male, respectively, and mean age ranged 39.0-40.2 years. Symptoms most reported by IP, non-refractory IP, refractory IP, and MEUC patients were abdominal pain (33.8%, 26.5%, 41.7%, 26.0%), fatigue/tiredness (22.7%, 20.4%, 25.2%, 23.8%) and bowel urgency (22.7%, 25.7%, 19.4%, 23.6%). According to Mayo scores at consultation, 40.3% of IP, 44.9% of non-refractory IP, 34.9% of refractory IP, and 50.4% of MEUC patients were in remission. Since diagnosis, 33.5% of IP, 71.8% of refractory IP, and 69.1% of MEUC cohorts had received AT. Conclusion Patients with IP experience a similar symptom burden to the MEUC population, despite currently available treatments for UC. The high AT use and low rate of remission indicates undertreatment of IP patients and a need for therapies with proven efficacy in this population, particularly after conventional therapy use. 1. Harbord et al. J Crohns Colitis. 2017 Jul 1;11(7):769-784.

P568 Clinical relevance of baseline and change in Urgency Numeric Rating Scale score for mirikizumab treatment for Ulcerative Colitis

Abstract Background Mirikizumab (MIRI), an anti-IL-23p19 antibody, has demonstrated efficacy/safety in moderately-to-severely active ulcerative colitis (UC) Phase 3 trials (LUCENT-1 and -2; NCT03518086, NCT03524092). This analysis evaluated induction and maintenance efficacy of MIRI among patients with different baseline (BL) bowel urgency severity. Methods In LUCENT-1, patients were randomized to receive 3 intravenous doses of 300mg MIRI or placebo (PBO); 1 every 4 weeks (Q4W). In LUCENT-2, responders to MIRI induction at W12 were rerandomized to subcutaneous 200mg MIRI or PBO Q4W through W40 (52W continuous treatment). Endpoints: clinical response, clinical remission, endoscopic remission, symptomatic remission at W12 and W52 (definitions in figure legend), Urgency Numeric Rating Scale ([UNRS]: 11-point scale from 0 [no urgency] to 10 [worst possible urgency]). Analysis: Fisher's exact test with non-responder imputation by patient induction BL UNRS score: 0-3, 4-6, and 7-10; score cut-offs based on ≥3 being a clinically meaningful improvement (JPRO 2022;6:114). Results Number of patients by BL UNRS score of 0-3, 4-6, or 7-10: W12 – 149, 437, 576 patients, respectively; W52 – 70, 215, 259 MIRI responders. At W12 and W52, a significantly greater proportion of MIRI-treated patients achieved clinical response, clinical remission, endoscopic remission, and symptomatic remission, regardless of UNRS score group at induction BL, for all comparisons except W52 clinical remission score 0-3 (Figure 1). In general, across clinical endpoints and regardless of BL UNRS score, MIRI treatment improved UNRS scores at W12 and W52 for a majority of patients, regardless of achievement of the clinical endpoint, although to a lesser extent when not achieved. MIRI treatment improved UNRS scores at W12 and W52 to a greater extent than PBO treatment regardless of achievement of clinical endpoint (Table 1; clinical remission data shown). Regardless of BL UNRS score, individual-point score shift data (not shown) illustrated that score shifts generally were distributed across lower scores at W12 and W52 than BL. This is relevant since Dubinsky and colleagues (JPRO 2022;6:31) demonstrated that a UNRS 1-2-point change in score can be important to a patient. Conclusion Regardless of BL bowel urgency severity based on UNRS score, MIRI is efficacious in achieving symptomatic, endoscopic, and clinical endpoints in UC patients. MIRI improves bowel urgency severity vs PBO even if clinical endpoints are not achieved. Observing shifts in UNRS scores along the UNRS scale, regardless of starting point, may aid in understanding a patient’s efficacy outcomes. These results support MIRI’s efficacy in bowel urgency and the clinical relevance of bowel urgency severity assessment over time.

P285 Communicating Needs and Features of IBD Experiences (CONFIDE) Survey: European and US Patient and Health Care Professional Perspectives on the Broad Impact of Bowel Urgency in Ulcerative colitis

Abstract Background Bowel urgency (BU) affects quality of life and psychosocial function of patients with moderate-to-severe ulcerative colitis (UC). This study used data from the Communicating Needs and Features of IBD Experiences (CONFIDE) survey to explore the patient and health care professional (HCP) perceptions on the broad impact of BU on patients’ emotions and daily lives. Methods Online, quantitative, cross-sectional surveys were conducted among patients with moderate-to-severe UC and HCPs in Europe (France, Germany, Italy, Spain, UK), the United States (US) and Japan. Data from Europe and US are presented here. A 7-point scale was used to rate the emotional impact of BU (Patients: 1=does not make me feel like this at all, 7=makes me feel like this a great deal; HCPs: 1=patients do not experience at all, 7=patients experience a great deal) and interference of BU with 12 different aspects of patients’ daily lives (Patients: 1=does not interfere, 7=interferes a great deal; HCPs: 1=no impact on patients and 7=impacts patients a great deal). Results Surveys were completed by 556 patients and 503 HCPs in Europe and 200 patients and 200 HCPs in the US. Among patients experiencing BU in the past month (Europe:30%, US:47%), most reported emotional impacts due to BU (mean rating [MR]≥4.1), as did the HCPs (MR≥5.2). In Europe, patients felt embarrassed when having to run to the bathroom due to BU (MR=5.0); HCPs reported that patients felt anxious/nervous due to BU as well as panic and embarrassment when having to run to bathroom due to BU (MR=5.8 each; Figure). In the US, similar to patients (MR=4.8), HCPs (MR=5.8) perceived their patients felt anxious/nervous due to BU. Impacts of BU on daily life were reported by patients (MR≥4.2) and HCPs (MR≥4.6). In Europe, patients reported a high impact on spontaneous activities (MR=5.1); HCPs reported a high impact on patients’ ability to travel (MR=5.8; Table). In the US, patients reported a high impact of BU on the choice (variety) and quantity of food/drinks (MR=5.2 each); HCPs perceived a high impact on patients’ spontaneous activities and ability to travel (MR=5.7 each). While most HCPs (Europe:58%, US:54%) ranked BU among top five most impactful symptoms, it was not among the top three most impactful symptoms on treatment decisions. Conclusion In both Europe and US, BU affected patients emotionally and limited their ability to travel and make spontaneous plans. Despite the broad impact of BU from both HCP and patient perspectives, with HCPs perceiving (numerically) a higher impact than patients, it was not among the top three most impactful symptoms on HCPs’ treatment decisions. Increased awareness of BU among HCPs is needed when making treatment decisions for patients with UC.

DOP70 Prevalence and severity of bowel urgency in Crohn’s Disease: Results from the Communicating Needs and Features of IBD Experience (CONFIDE) Survey

Abstract Background Bowel urgency (BU) affects patients with Crohn’s disease (CD); however, its prevalence and severity are unclear. Here, data from Communicating Needs and Features of IBD Experiences (CONFIDE) study were used to understand the burden and impact of BU among patients with moderate-to-severe CD. Methods CONFIDE is an online, quantitative, cross-sectional survey exploring the experiences and impact of symptoms on patients with CD or ulcerative colitis in Europe (France, Germany, Italy, Spain, and UK), United States (US) and Japan. Criteria based on previous treatment, steroid use, and/or hospitalization defined moderate-to-severe CD. Patients were asked about bowel movement deferral time with response options ranging from able to wait ≥15 minutes (mins) to sometimes unable to make it to the bathroom in time. Patients currently experiencing BU (in last month) rated BU severity in the last 3 days using the Urgency Numeric Rating Scale (NRS, 0-10), a content-validated patient-reported instrument. CD data from Europe and US are presented here using descriptive statistics. Results Surveys were completed by 547 European (male [M]=55.4%, mean age 38 years) and 215 US (M=54.9%, mean age 40.9 years) patients with CD. Current BU (over the past month) was reported by 38% of patients in Europe and 42.3% in US. More than one-third of all patients in both Europe and US reported that over the last 3 days, they needed to get to the bathroom within 5 mins, and 1.8% European and 2.8% US patients were sometimes unable to make it to the bathroom in time. Among patients who reported currently experiencing BU, 46% reported the need to get to the bathroom within 5 mins and 3% reported sometimes being unable to make it to the bathroom in time in both Europe and US. Shorter deferral times were reported by those with higher mean Urgency NRS scores (Table). Mean (SD) Urgency NRS scores in patients with a deferral time <5 mins vs those with a deferral time >5 mins were 7.0 (1.7) vs 6.5 (2.1) among European and 7.3 (1.5) vs 6.7 (1.9) among the US patients. Most European and US patients reported experiencing BU, BU-related accidents, and/or wearing diaper/pad/other protection due to fear/anticipation of BU-related accidents at least once a month in past 3 months (Figure). Conclusion Patients with moderate-to-severe CD reported similar experiences of BU in the Europe and US, with most patients reporting currently experiencing BU and wearing diaper/pad/protection due to fear of BU-related accidents at least once a month. Patients currently experiencing BU had short deferral times, often having to reach the bathroom in ≤5 mins. Given the substantial burden and impact, BU should be considered when assessing patients with CD.

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< .0001). Additionally, BU was associated with a higher median rate of hospitalizations in the previous 12 months (Δ=1; p<0.001).Patients with BU reported a higher degree of RB(33.3%) and SF(50,7%) than patients without BU (p< .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<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<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

Clinical usefulness of hypoxia imaging colonoscopy for the objective measurement of ulcerative colitis disease activity

Background and AimsColonic mucosal hypoxia is associated with mucosal inflammation in ulcerative colitis (UC). We aimed to assess the clinical usefulness of hypoxia imaging colonoscopy for the assessment of clinical, endoscopic, and histologic disease activities of UC. MethodsThis was a retrospective cohort study comprised of 100 consecutive UC patients who underwent hypoxia imaging colonoscopy between September 2022 and September 2023 at the University of Tsukuba Hospital. We measured colonic tissue oxygen saturation (StO2) at the biopsy sites and compared StO2 values between different disease activities. We used receiver operating characteristic (ROC) analysis to calculate the area under the ROC curve (AUROC). ResultsWe identified a significant correlation between rectal StO2 and the Simple Clinical Colitis Activity Index, with moderate accuracy to predict bowel urgency at a 40.5% cutoff (AUROC 0.74, 95% CI 0.62-0.87). Our analysis of 490 images showed median StO2 values for Mayo endoscopic subscores (MES) 0, 1, 2, and 3 as 52% (IQR 48%-56%), 47% (IQR 43%-52%), 42% (IQR 38.8%-47%), and 39.5% (IQR 37.3%-41.8%), respectively. Differences for all pairs were significant. Median StO2 was 49% (IQR 44%-54%) for Geboes scores 0-2, significantly higher than histologically active disease (Geboes score ≥ 3). At a colonic StO2 cutoff of 45.5%, AUROCs for endoscopically and histologically active diseases were 0.79 (95% CI 0.74-0.84) and 0.72 (95% CI 0.66-0.77), respectively. ConclusionsStO2 obtained by hypoxia imaging colonoscopy is useful for assessing clinical, endoscopic, and histologic activities of UC, suggesting StO2 may be a novel and objective endoscopic measurement.

Association of Bowel Urgency With Quality-of-Life Measures in Patients With Moderately-to-Severely Active Ulcerative Colitis: Results From Phase 3 LUCENT-1 (Induction) and LUCENT-2 (Maintenance) Studies.

Improvement in bowel urgency (BU) was associated with better clinical outcomes in phase 3 LUCENT-1 (induction) and LUCENT-2 (maintenance) studies in moderately-to-severely active ulcerative colitis (UC). We assessed association of BU with quality-of-life (QoL) outcomes. LUCENT-1: 1162 patients randomized 3:1 to intravenous mirikizumab 300mg or placebo every 4 weeks (Q4W) for 12 weeks. LUCENT-2: 544 mirikizumab induction responders re-randomized 2:1 to subcutaneous mirikizumab 200mg or placebo Q4W through Week (W) 40 (W52 of continuous treatment). Patients reported BU severity in the past 24 hours using a validated Urgency Numeric Rating Scale (NRS). In patients with baseline Urgency NRS ≥3, the association between BU Clinically Meaningful Improvement (CMI; ≥3-point decrease) and remission (score 0 or 1) with patient-reported outcomes was assessed at W12 and W52. A significantly greater proportion of patients with versus without BU Remission achieved IBDQ remission (W12: 87.3% vs 42.7%, P < .0001; W52: 91.4% vs 45.5%, p < .0001). Similarly, BU Remission was associated with more patients achieving CMI in SF-36 Physical Component Summary (W12: 69.0% vs 44.4%, P < .0001; W52: 77.5% vs 42.1%, P < .0001) and Mental Component Summary (W12: 53.5% vs 41.0%, P = .0019; W52: 62.0% vs 38.3%, P < .0001) scores. At W12 and W52, patients with BU CMI or Remission showed significant improvements in EQ-5D-5L and Work Productivity and Activity Impairment:UC scores. Significant improvements were also seen in fatigue, abdominal pain, and nocturnal stool. In patients with moderately-to-severely active UC, improvement in BU was associated with improved QoL in phase 3 LUCENT-1 and LUCENT-2 studies. LUCENT-1: NCT03518086; LUCENT-2: NCT03524092.

A Clinical Review on Ulcerative Colitis (Colon Cancer)

Ulcerative colitis (UC) is also known as colon cancer or colorectal cancer, a chronic inflammatory condition of the large intestine (colon and rectum). It comes under blood in stool, bowel urgency, fatigue, low energy, and rarely fever. Inulcerative colitis, the part of the colon's inner lining of unknown etiology involves the gastrointestinal tract. More than 80% of ulcerative colitis patients have the lining tissue of the inner rectum inflamed or has proctosigmoiditis, and less than 20% of patients haveextensive colitis. The case of UC has risenworldwide in the recent few decades, particularly in growing countries. The high-risk factors are family history, gender, race, and environmental factors contributing are smoking, infection taking Antibiotics, and NSAIDs. In 2013, Over 350,000 new cases of ulcerative colitis and over 125,000 Patients deaths were reported in the USA. Ulcerative colitis is different from Crohn's disease. However,in more the 50% of patients with mildsymptoms of proctosigmoiditis, some patients show proximal extension, and for some patients,opposition occurs with mild symptoms. Moreover, it is essential to identify the patients with some symptoms of ulcerative colitis to clinical risk factors that will help identify which patients are in the critical or higher stage of the disease proximal extension.The ulcerative colitis usually devolves between 20 to 30 years.