Endoscopic Remission Rates Research Articles

P1005 Dose escalated Infliximab in Inflammatory Bowel Disease - Crohn's Colitis Cure (CCC) Data Insights Program

Abstract Background Infliximab (IFX) is a monoclonal antibody targeting TNF-α and remains a cornerstone of management of Inflammatory Bowel Disease (IBD). A significant number of people with IBD on standard IFX therapy have persistent disease activity and require dose escalation (DE). In Australia and many other healthcare systems, funding through pharmaceutical benefits schemes is only available for standard dosing. We aim to evaluate the role of DE IFX and patient outcomes in a real-world cohort. Methods We performed a cross-sectional observational study using data from Crohn’s Colitis Care, a cloud-based IBD specific electronic medical record used in routine care in Australasia. Data were extracted in November 2023 from 14 private and public care centres. DE was defined as dosing interval <8 weeks and/or dosing >5mg/kg. We examined IBD outcomes prior to and 12 months post DE. Results A total of 1725 people received IFX, with DE in 762 (44.2%); 65% had Crohn’s Disease (CD), 33% had ulcerative colitis (UC) and 2% IBD-Unclassified (IBD-U), with a relatively even gender distribution (52.5% male). In the DE cohort, median age was 37 years (IQR 27-49); median age at diagnosis was 23 years (IQR 16-32) and median disease duration 11.6 years (IQR 5.8-17.3). DE and standard dose cohorts did not differ by IBD classification, gender, disease duration, age or age at diagnosis. Median drug level was higher 12-months post DE (8.16μg/ml vs 3.65 μg/ml). Faecal calprotectin (FCP) remission rate (FCP <250μg/g) was higher 12 months post DE, as was endoscopic remission rate and patient reported outcome remission (Table 1). The rate of systemic corticosteroids was lower 12 months post-DE than pre-DE. In the DE-IFX cohort, measures of healthcare utilisation were lower 12-months post-DE; hospitalisation (56 vs 146; p<0.001), surgical interventions (41 vs 61; p=0.040), endoscopic procedures (210 vs 397, p<0.001) and radiological investigations (243 vs 343; p<0.001). Conclusion Within a large Australasian IBD cohort, many individuals on IFX required DE. DE IFX was associated with improved measures of remission as well as a reduction in several measures of healthcare utilisation. These data will be used to undertake formal health economic analysis to determine the price points at which DE is cost-effective; additional data on quality of life and indirect healthcare costs will be important to include for a robust holistic assessment of value in care.

P847 Effectiveness of tofacitinib in ulcerative proctitis compared to left sided colitis and pancolitis

Abstract Background Ulcerative proctitis (UP), though associated with high symptom burden and poor quality of life, is excluded from most of the randomized controlled trials in UC. We aimed to analyse the effectiveness of tofacitinib in UP, and compare it to that in left sided colitis (LSC) and pancolitis (PC). Methods This was a prospective observational cohort study. Patients with either steroid-dependent or refractory ulcerative colitis, who received tofacitinib, were divided into three groups based on the disease extent [UP, LSC and PC]. The primary outcome was comparison of proportion of patients in clinical remission in the three groups, at weeks 8, 16 and 48. Safety outcomes were reported using incidence rate per patient year of exposure. Results Clinical remission was achieved in 47%(15/32), 24%(23/94), and 43%(23/54) of patients at week 8, 56%(18/32), 37%(35/94), and 55%(30/54) of patients at week 16, and 59%(19/32), 38%(36/94), and 24%(13/54) of patients at week 48 in groups UP, LSC and PC, respectively. (Figure 1) Corticosteroid-free clinical remission rates were significantly higher in patients in groups UP at week 48. Five (15%) patients with UP were primary non-responders to tofacitinib at week 16, while three (9%) patients had secondary non-response at week 48. The median fecal calprotectin values at week 8 were 119.5 (53.75-611.25), 134 (63-456) and 208 (48.25-876) in patients with UP, LSC and PC, respectively. Similarly at week 48, the median fecal calprotectin values were the lowest in patients with UP (57[36-99]) as compared to patients with LSC (113[41-572]) and PC (150[89-1562]). The endoscopic remission rates at week 48 were similar in all the three groups (31%, 21% and 18% in groups UP, LSC and PC, respectively (UP vs LSC, p=0.25; UP vs PC, p=0.18; LSC vs PC, p=0.68). The probability of sustained clinical response was highest in patients with UP (cumulative probability of maintaining response 0.88) followed by groups LSC (cumulative probability of maintaining response 0.74) and PC (cumulative probability of maintaining response 0.60). The between group difference, was significant (Log Rank, p=0.03). (Figure 2) Patients with UP had the lowest incidence of adverse effects. Conclusion The effectiveness of tofacitinib in inducing and maintaining remission is greater in patients with UP compared to LSC and PC.

P366 Risk factors and outcomes of chronic antibiotic-refractory pouchitis in Korean ulcerative colitis patients: a single center retrospective study

Abstract Background Chronic inflammation of the pouch after total proctocolectomy with ileal pouch-anal anastomosis (IPAA) remains a morbid complication in ulcerative colitis (UC). The goal of this study was to investigate risk factors and clinical outcomes of chronic antibiotic-refractory pouchitis (CARP) in Korean patients with UC. Methods This was a single center retrospective study on patients with UC who underwent total proctocolectomy with IPAA at Asan Medical Center in Korea between January 1987 and December 2022. CARP was defined as failure to respond to a 4-week course of a single antibiotic, needing more than 4 weeks of therapy with 5-aminosalicylates, steroids, immunomodulators or biologics/small molecules, while chronic antibiotic-dependent pouchitis (CADP) was defined as more than 3 episodes of pouchitis per year or persistent symptoms requiring long-term antibiotics to maintain disease remission. Primary outcomes were endoscopic remission defined as complete mucosal healing of chronic pouchitis and pouch failure defined as the requirement of diverting loop ileostomy or pouch excision. Univariable and multivariable logistic regression analysis were used to identify risk factors of CARP. Results A total of 251 patients were included and 232 were analyzed (Male, 57.3%; Current smoker, 13.4%; Median age at surgery, 44 years; Disease duration at surgery, 4 years; Previous exposure to biologics/small molecules, 23.7%; Extra-intestinal manifestations, 8.2%; Preoperative cytomegalovirus infection, 19.4%). The most common cause of surgery was steroid refractoriness (50.9%), followed by dysplasia/colorectal cancer (26.7%). The median time from surgery to chronic pouchitis was 48 months (interquartile range 23.5–100.0). Among 74 patients (31.9%) with chronic pouchitis, 31 patients (13.4%) were CARP and 43 patients (18.5%) were CADP. The most frequent endoscopic phenotype according to Chicago classification was focal inflammation of the pouch in all groups (chronic pouchitis, 47.3%; CARP, 35.5%; CADP, 55.8%). Patients with CARP were less likely to have concomitant probiotics compared with CADP (29.0% vs 72.1%; p<0.01). Endoscopic remission rate in chronic pouchitis, CARP, and CADP were 14.9% (11/74), 9.7% (3/31), and 18.6% (8/43), respectively (Table 1). Pouch failure rate in chronic pouchitis, CARP, and CADP were 13.5% (10/74), 16.1% (5/31), and 11.6% (5/43), respectively (Table 1). In a multivariable analysis, current smoking status was positively associated with CARP development (OR: 3.56; 95% confidence interval 1.33–9.52; p=0.01). Conclusion Current smoker with UC who underwent IPAA had a higher risk of CARP. Concomitant use of probiotics was less likely to be associated with developing CARP.

P936 Ultrasound Transmural Remission in Crohn's disease: Different Rate between First and Second Line of Biological Therapy

Abstract Background Ultrasound transmural remission in Crohn’s disease (CD) has been associated with improved long-term clinical outcomes including reduced hospitalization, surgery, escalation of treatment, and a decrease in clinical relapse over endoscopic remission alone. Albeit transmural remission rate (TRR) in CD patients treated with anti-TNF drugs in first line has been well explored, data on TRR using vedolizumab (VDZ) or ustekinumab (UST) as second-line therapy for CD are still limited. The aim of this study was to evaluate the TRR in CD patients in maintenance treatment, comparing adalimumab (ADA) in first line with VDZ/UST in second line. Methods From 2018 to 2022 we performed a real world observational longitudinal study evaluating the TRR in all consecutive CD patients in a 2-years maintenance treatment with ADA in first line compared with those treated by VDZ or UST in second line. HBI, fecal calprotectin (FC), SES-CD, and bowel wall thickness (BWT) at ultrasound were analyzed in all patients at the baseline (T0) and after 2 years of maintenance treatment (T1). Clinical remission was defined when HBI was <4. Endoscopic remission was defined when SES-CD was <2. Transmural remission was defined when BWT was <3 mm at a "per-patient" analysis. In accordance with recent literature, laboratory remission was defined when FC was <94 ug/gr. Results One hundred and sixty-one CD patients (78 ADA, 41 VDZ, 42 UST) were included in the study. At T1, TRR was recorded in 39.7% of CD patients treated in first line with ADA, and in 17.1% and 21.4% for VDZ and UST, respectively, in second line (ADA vs VDZ/UST: p<0.05; VDZ vs UST: p 0.6). Endoscopic remission rate was 50% for patients treated in first line with ADA, and 31.7% and 35.7% for second line VDZ and UST, respectively (ADA vs VDZ/UST: p<0.05; VDZ vs UST: p 0.7). Laboratory remission rate was 53.8% for patients treated in first line with ADA, and 29.3% and 35.7% for VDZ and UST in second line, respectively (ADA vs VDZ/UST: p<0.05; VDZ vs UST: p=0.5). Clinical remission rate was 58.9% for patients treated in first line with ADA, and 43.9% and 47.6% for second line VDZ and UST, respectively (ADA vs VDZ/UST: p=0.09; VDZ vs UST: p=0.2). Conclusion Our findings showed that in CD patients in maintenance treatment with biologics, ADA in first line showed a higher TRR compared with VDZ/UST in second line. Moreover, VDZ and UST showed similar TRR and other outcomes when used in second line.

P965 Ulcerative proctitis treated with biologics: is it too hard to treat?

Abstract Background Patients with ulcerative proctitis are widely considered a challenging population because the reported reduced response rate to conventional medical treatment. On the other hand, data on the role of biological therapies in this specific cohort are currently scarce Methods We retrospectively evaluated all patients with proctitis (defined as the mucosal inflammation of only the rectum with ulcerative colitis confirmed by histology) treated with biologics (infliximab, adalimumab, vedolizumab -VDZ-, ustekinumab -UST) and tofacitinib (TOFA) at four referral centers in the last 5 years. All patients were treated with concomitant topical mesalamine. We included in this study only patients who underwent colonoscopy at baseline and after 52 weeks of treatment, in order to evaluate therapeutic response in terms of mucosal healing (defined as a Mayo Endoscopic Score -MES- <2), besides that clinical remission (defined as a Partial Mayo Score -PMS- <2 without oral or topical corticosteroid therapy). We collect clinical and demographic data, as well as fecal calprotectin (FC) and C-Reactive Protein (CRP) levels at baseline and after the induction of therapy Results Among 64 patients enrolled (age 50.8±16.5 years, 29 [45.3%] women), 33 (51.6%) were treated with anti-TNF), 15 with VDZ, 13 with UST, and 3 with TOFA. Globally, 51 (79.7%) patients achieved clinical remission and 37 (57.8%) patients achieved endoscopic remission at 52 weeks. There were no group differences in age, sex, BMI, disease duration, PMS, MES, drug, or baseline CRP levels between patients achieving or not either clinical or endoscopic remission. Baseline calprotectin levels were lower in patients who achieved endoscopic remission (median [IQ range] 297 [158, 475] versus 442 [230, 1545] µg/mL, p=0.036), but not in those who achieved clinical remission. After the induction phase, lower calprotectin levels were observed in patients achieving clinical (46 [15, 166] versus 553 [72, 1649] µg/mL, p=0.001) and endoscopic remission (38 [15, 112] versus 328 [52, 2171] µg/mL, p=0.0002), compared with non-responders. The effects of post-induction calprotectin levels on clinical remission (β= -0.001, p=0.020) and endoscopic remission (β= -0.007, p=0.006) remained significant in multivariable models adjusted for age, sex, BMI, disease duration, and biological treatment. A cut point of 200 µg/mL post-induction was identified to predict endoscopic remission (sensitivity 92%, specificity 64%, ROC AUC 0.781) Conclusion High rates of clinical and endoscopic remission with biological therapies could be achieved in patients with ulcerative proctitis. Fecal calprotectin levels after the induction of biological therapies seem to predict the therapeutic response in patients with ulcerative proctitis

P962 Clinical and endoscopic remission at 3 months after Acute Severe Ulcerative Colitis is predictive of maintenance therapy outcomes at 12 months - Results from PREDICT UC

Abstract Background The optimal maintenance regimen after rescue therapy for Acute Severe Ulcerative Colitis (ASUC) is unknown. We aimed to evaluate prospectively the impact of different maintenance regimens after successful infliximab (IFX) rescue, along with factors associated with Month 12 remission. Methods Clinical responders at 3 months from PREDICT UC, a randomised trial (NCT02770040) comparing standard and intensified IFX rescue strategies, were evaluated in this prospective cohort study up to Month 12. Maintenance therapies were as follows: (1) Thiopurine monotherapy (azathioprine or mercaptopurine) for thiopurine naïve patients or prior suboptimal thiopurine therapy (TP); (2) Combination thiopurine and IFX therapy 5mg/kg 8-weekly for thiopurine-experienced patients (IFX+TP combo); (3) IFX monotherapy 5mg/kg 8-weekly for thiopurine-intolerant patients (IFX mono). All patients received oral 5-aminosalicylates. Clinical and endoscopic assessments were performed at baseline (Month 3) and Month 12. Clinical remission was defined as a partial Mayo score of 0-1 and endoscopic remission as Mayo Endoscopic Score (MES) of 0-1. Results Of 138 patients randomised, 79 entered the maintenance phase. Of these, 56 (71%) received TP, 16 (20%) received IFX+TP combo and 7 (9%) received IFX mono. Baseline characteristics were similar across the 3 maintenance groups. At 12 months, 42 patients (53%) were in clinical remission, 44 patients (56%) were in endoscopic remission, and one patient underwent colectomy. The 3 maintenance groups had similar rates of clinical remission (TP 55%, IFX+TP combo 56%, IFX mono 29%; P=0.39) and endoscopic remission (TP 55%, IFX+TP combo 56%, IFX mono 57%; P=0.99) at 12 months. Clinical Remission On univariable and multivariable analysis, no factors were associated with clinical remission at 12 months, including baseline CRP, albumin, partial Mayo score, MES, UCEIS or maintenance strategy. Endoscopic Remission Factors associated with endoscopic remission at 12 months included baseline partial Mayo score of 0 (OR 3.36, 95% CI 1.24-9.10, P=0.017), MES of 0-1 (OR 3.48, 95% CI 1.08-11.27, P=0.037) and UCEIS of 0-1 (OR 3.30, 95% CI 1.24-8.76, P=0.016). However, a partial Mayo score cut-off of 0-1 did not reach significance (OR 3.46, P=0.09). No factors associated with endoscopic remission were identified on multivariable analysis. Conclusion In steroid-refractory ASUC patients who received IFX rescue, clinical and endoscopic remission at Month 3 were associated with endoscopic remission at Month 12, particularly among patients with greater depth of remission. Month 3 assessment helps identify patients at higher risk of disease progression for whom more intensive treatment may be required.

P601 Intestinal ultrasound correlates with clinical, biochemical, endoscopic and histologic biomarkers in patients with Ulcerative Colitis: a cross-sectional study

Abstract Background Intestinal ultrasound (IUS) is emerging as a non-invasive monitoring tool in patients with ulcerative colitis (UC). Our goal was to correlate IUS with clinical, biochemical, endoscopic and histological activity. Methods Cross-sectional multicentric study of patients with left (E2) or extensive (E3) UC. Consecutive patients were included and clinical (Patient-Reported Outcome (PRO2) and Simple Clinical Colitis Activity Index (SCCAI)), biochemical (fecal calprotectin (FCal) and C-reactive protein (CRP)), endoscopic (Mayo endoscopic sub-score (sMayo)) and histological (Nancy score) activity were evaluated. IUS activity was characterized by Milan Ultrasound Criteria (MUC). Clinical, biochemical, ultrasonographic, endoscopic and histologic remission were defined as SCCAI≤2, FCal<250 ug/g, MUC<6.2, sMayo=0 and Nancy=0, respectively. All evaluations were performed within 1 month. Pathologist was blinded to endoscopic and IUS results. In patients in IUS remission, the sigmoid colon was considered for analysis. Results 58 patients with UC were included (55% men, with a mean-age of 38 (+/-17) years, 65% with E2 UC). Clinical, biochemical, ultrasonographic, endoscopic and histologic remission occurred in 53%, 53%, 53%, 31% and 12% of the patients, respectively. The most affected segment by both IUS and endoscopy was the sigmoid colon (34.5% and 41.4%, respectively). In our cohort, IUS activity had a strong correlation with PRO2 (r=0.778, p<0.001), SCCAI (r=0.810, p<0.001) and endoscopic activity (r=0.758, p<0.001), and a moderate correlation with FCal (r=0.517, p<0.001), CRP (r=0.402, p<0.001) and histological activity (r=0.475, p<0.001). We observed a consistent increase in the bowel wall thickness (BWT) and MUC score as the sMayo raised. Accordingly, patients with endoscopic activity presented higher BWT and MUC score, when compared to patients in endoscopic remission (Table 1). On the other hand, patients in IUS remission showed higher rates of clinical (90% vs 10%, p<0.001) biochemical (74% vs 26%, p<0.001) and endoscopic remission (94% vs 6%, p<0.001), with a trend towards higher rates of histologic remission (86% vs 14%, p=0.054). Conclusion In our cohort, IUS activity had a moderate to strong correlation with clinical, biochemical, endoscopic and even histologic activity. Additionally, patients with endoscopic activity presented worse IUS activity, suggesting this method as a reliable non-invasive monitoring tool in UC patients.

P1012 Dose escalated Ustekinumab in Inflammatory Bowel Disease - Crohn's Colitis Cure (CCC) Data Insights Program

Abstract Background Ustekinumab is a human monoclonal antibody targeting interleukin-12 and 23 with established efficacy in inflammatory bowel disease (IBD). Many people receiving ustekinumab do not achieve adequate or sustained response to standard dosing and require dose escalation (DE). We aimed to investigate the frequency and outcomes of escalated dosing regimens in an Australasian cohort. Methods Crohn’s Colitis Care (CCCare) is a cloud-based IBD-specific electronic medical record used in routine care across Australia and New Zealand. Data feeds continuously into a de-identified clinical quality registry (CQR). Data were interrogated in November 2023 comparing outcomes and healthcare utilisation prior to and at 12 months post ustekinumab DE. DE was defined as maintenance dosing >90mg subcutaneously Q8 weekly and/or additional induction doses. Results A total of 790 people received ustekinumab, with 43.4% on DE therapy. Most of the cohort had Crohn’s disease (86.1%), followed by ulcerative colitis (11.3%) and IBD-unclassified (1.6%). The median age for the total cohort was 40 years (IQR 30-52) with an even gender distribution (50.3% female). The median age at diagnosis was 25 (IQR 18-38) with a median time to DE of 6 months (IQR 1-15). Age, age at diagnosis and disease duration did not significantly differ between DE and standard dose cohorts. Almost all people with IBD on DE ustekinumab continued on therapy beyond 12 months (84.5%). Rates of faecal calprotectin remission (<250ug/g), endoscopic remission and patient reported outcome (PRO2) remission were higher 12 months post DE (Table 1). Systemic steroid requirements fell significantly 12 months post DE. The number of endoscopies and radiological investigations fell at 12 months post DE, while the rates of hospital admissions did not significantly differ between the DE and standard cohorts. Clinical assessments (per person) reduced from 1.2 pre-DE to 0.9 post DE. Conclusion In a large real-world Australasian cohort of people receiving ustekinumab for IBD, close to half required DE. DE led to reduced systemic steroid use and improved endoscopic, PRO2 and FCP remission rates at 12 months. These data can be used to perform health economy analysis to determine the price points at which DE is cost effective, with additional data on quality of life and indirect healthcare costs being important to include for a robust holistic assessment of value in care.

P959 Dose escalated vedolizumab in Inflammatory Bowel Disease - Crohn's Colitis Cure (CCC) Data Insights Program

Abstract Background Vedolizumab is a gut specific integrin antagonist with established efficacy in inflammatory bowel disease (IBD). Many people with IBD fail to achieve adequate or sustained response to standard dosing, thus requiring dose escalation (DE). We aimed to explore the need for escalated dosing and subsequent outcomes in a large real-world cohort. Methods We utilised data from the CCC registry entered during routine clinical care at 14 centres across Australia and New Zealand. Data were extracted in October 2023 and included patients on intravenous (IV) and subcutaneous (SC) therapy. DE was defined as maintenance dosing > 108mg SC fortnightly, > 300mg IV Q8weekly and/or additional induction doses. We examined data prior to and at 12 months post DE. Results 919 people with IBD received Vedolizumab, with 28% (n=261) receiving DE therapy. Median age for the DE cohort was 40 years (IQR 29-56) with median age at diagnosis 26 (IQR 19-39). Median age, age at diagnosis, disease duration and BMI did not vary significantly between the DE and standard dosing cohorts. Most of the DE cohort had Crohn’s (60%) followed by ulcerative colitis (38%) and IBD-unclassified (2%). Half the DE cohort was female (49.8%) with median time to dose escalation being 6 months. 57% (n=111) continued on DE Vedolizumab after 12 months. Median drug level (where measured) increased from 10.3mg/L pre-DE to 19.8mg/L post. Rates of faecal calprotectin (FCP) remission, (FCP <250ug/g) increased at 12 months post DE as did rates of PRO2 and endoscopic remission (p=0.007, 0.034 & 0.016 respectively). Improved remission rates coincided with decreased systemic steroid requirements, which fell by >50% at 12 months post DE (p=0.001). Hospital admissions and radiological investigations were unchanged over the study period, however the need for endoscopic assessment decreased 12 months post DE. Patients receiving DE therapy had increased encounters healthcare providers, with more clinical assessment and Healthline calls at 12 months post DE (p=0.001 & 0.001 respectively). Conclusion In an Australasian cohort of people with IBD, over a quarter of individuals receiving Vedolizumab therapy required DE. DE Vedolizumab correlated with improved endoscopic, PRO2 and FCP remission rates at 12 months with reduced steroid use. As biosimilars reduce the cost of DE therapy, further research beyond 12 months examining remission rates, healthcare utilisation and cost analysis in more detail is needed.

P872 PREDICT UC: Optimising Infliximab Induction therapy for Acute Severe Ulcerative Colitis – A Randomised Controlled Trial

Abstract Background The optimal dosing strategy of infliximab (IFX) in Acute Severe Ulcerative Colitis (ASUC) is unknown. We compared intensified and standard dose IFX strategies in ASUC. Methods In this open-label randomised trial (NCT02770040), patients from 13 Australian centres with intravenous steroid-refractory ASUC were randomised to receive a first dose of 10mg/kg or 5mg/kg IFX in a 1:2 ratio. Patients in the 10mg/kg group (intensified induction [II]) received a second dose at day 7 or earlier at time of non-response; all 5mg/kg patients were re-randomised 1:1 to standard (SI) or accelerated induction (AI), which produced three induction groups: II, SI and AI. SI patients received 5mg/kg at week 0, 2 and 6, with an extra 5mg/kg dose before day 7 if non-response. AI patients received 5mg/kg at week 0, 1 and 3, with the week 1 dose increased to 10mg/kg and given earlier if non-response. Primary outcome: clinical response by day 7 (reduction in Lichtiger score to <10, with decrease of ≥3 points and improvement in rectal bleeding and stool frequency to ≤4/day). Secondary outcomes compared induction regimens until month 3. Analysis was by intention to treat. Results Between July 2016 & September 2021, 138 patients were randomised; 46 received a first IFX dose of 10mg/kg and 92 received 5mg/kg. Primary outcome: day 7 clinical response was observed in 65% (30/46) of 10mg/kg vs 61% (56/92) of 5mg/kg patients (P=0.76). In the 5mg/kg group, the rate of day 7 response was numerically lower in those with albumin <25g/L vs ≥25g/L [47% (15/32) vs 68% (41/60), P=0.07]. No difference in clinical response was observed in the 10mg/kg group when stratified by albumin [64% (9/14) vs 66% (21/32) P>0.99]. There was no difference in time to clinical response, change in Lichtiger score or CRP from baseline to day 7. Two patients who received 10mg/kg IFX underwent colectomy in the first 7 days vs 0 in the 5mg/kg group (P=0.21). Comparison of induction regimens (II, SI & AI): no difference in clinical remission rates between weeks 2 and 6 were observed. AI and II groups had higher rates of combined clinical and biochemical remission compared to SI between weeks 2 and 6 (P=0.042). At 3 months, there was no difference in rates of endoscopic and steroid-free remission, as well as rates of colectomy (II 7%; SI 12%; AI 19%, P=0.20). Conclusion In steroid-refractory ASUC, a first dose of 10mg/kg or 5mg/kg IFX achieved similar clinical response rates by day 7. Patients receiving intensified or accelerated induction achieved clinical and biochemical remission earlier compared to standard induction; however, outcomes at three months were similar. Patients with a lower albumin may benefit from proactive intensified dosing strategies.

P542 Clinical decision support tool guided selective intensive induction strategy of ustekinumab in patients with Crohn’s disease: real-world evidence

Abstract Background Clinical decision support tool (CDST) of ustekinumab (UST) can predict the possibility of drug response1. However, the potential benefits of initial intensification induction therapy (IIT) to improve clinical outcomes for different responders has not been explored2. We aimed to evaluate the effectiveness and safety of the strategy of initial IIT for Crohn’s disease patients who exhibit varying responses based on UST-CDST. Methods This is a multicenter retrospective study included active Crohn’s disease patients who were low, intermediate and high probability responders according to UST-CDST (Figure 1). IIT was defined as intensive induction by 2 or 3 initial doses of a weight-based intravenous UST. The patients treated with standard therapy (ST) were identified as controls. The primary endpoint was corticosteroid-free clinical remission (CFCR) at week 24. The secondary endpoint was clinical remission, clinical response, endoscopic remission, endoscopic response, and CRP normalization at week 24. Propensity-matched analyses were applied to ensure comparability. Results A total of 296 patients were included, with 69 patients receiving IIT and 227 patients receiving ST. At week 24, in low-intermediate probability responders, IIT group was associated with higher rates of CFCR (72.3% vs 43.0%, OR 3.47 [95%CI 2.15-5.68], clinical remission (77.3% vs 47.1%, OR 3.82 [95%CI 2.33-6.37]), clinical response (78.1% vs 60.1%, OR 2.37 [95%CI 1.43-3.97]), endoscopic remission (50.6% vs 22.4%, OR 3.55 [95%CI 1.65-7.92]) and endoscopic response (83.1% vs 44.1%, OR 6.23 [95%CI 2.75-15.26]). CRP normalization were comparable. In high probability responders, all end points did not demonstrate statistically significant differences (Table 1). The cut-off UST trough concentration for predicting corticosteroid-free clinical remission was determined to be 1.43µg/mL, with an area under the curve (AUC) of 0.612, a sensitivity of 55.0%, and a specificity of 70.0%. No serious adverse events occurred. Conclusion Initial dose intensification induction in low-intermediate responders based on UST-CDST was superior to the ST in both clinical and endoscopic remission at week 24, which provide a novel strategy for stratifying patients at baseline. 1. Park J, Chun J, Yoon H, Cheon JH. Feasibility of a Clinical Decision Support Tool for Ustekinumab to Predict Clinical Remission and Relapse in Patients With Crohn's Disease: A Multicenter Observational Study. Inflamm Bowel Dis. 2023;29(4):548-554. 2. Ren H, Kang J, Wang J, et al. Efficacy of Ustekinumab Optimization by 2 Initial Intravenous Doses in Adult Patients With Severe Crohn's Disease [published online ahead of print, 2023 Aug 24]. Inflamm Bowel Dis. 2023; izad184.

OP10 Efficacy and safety of upadacitinib in patients with moderately to severely active Crohn’s Disease: results from the U-ENDURE long-term extension

Abstract Background Upadacitinib (UPA) is an oral Janus kinase inhibitor approved for the treatment of moderately to severely active Crohn’s disease (CD).1 The U-ENDURE (NCT03345823) maintenance study and long-term extension (LTE) evaluate the long-term efficacy and safety of UPA maintenance therapy. Here, we report the results of the U-ENDURE LTE. Methods Patients (pts) completing the U-ENDURE 52-week (wk) maintenance study were eligible to participate in the LTE and continue their previously assigned treatment (placebo [PBO], UPA 15 mg [UPA15] once daily [QD], or UPA 30 mg [UPA30] QD; blinded until the last pt completed maintenance wk52). Clinical response, clinical remission, endoscopic response, endoscopic remission, as well as high-sensitivity C-reactive protein (hs-CRP) and faecal calprotectin (FCP) were evaluated as-observed up to wk48 of the LTE among pts (PBO [N = 89], UPA15 [N = 107], UPA30 [N = 173]); excluding pts who received open-label UPA30 rescue therapy. Safety was assessed in all pts (PBO [N = 223], UPA15 [N = 221], UPA30 [N = 229]) from wk0 of the maintenance study up to LTE wk204 (cut-off date: 01 Aug 2023). Results At LTE wk0, the SF/APS clinical remission rates were 73.0%, 78.3%, and 80.3% for PBO, UPA15, and UPA30, respectively (Figure 1A). Similar rates were reported at LTE wk0 for CDAI clinical remission (PBO 75.3%, UPA15 81.3%, UPA30 80.9%; Figure 1B) and clinical response (CR-100: PBO 79.5%, UPA15 84.9%, UPA30 84.4%). Rates of clinical remission were stable through wk48 of the LTE. Endoscopic response (PBO 32.9%, UPA15 59.6%, UPA30 66.5%) and remission rates (PBO 27.8%, UPA15 42.4%, UPA30 47.3%) at LTE wk0 were sustained through wk48 with UPA while decreased with PBO (Figure 1C-D). At LTE wk0, the mean [95% CI] change from induction BL in hs-CRP was 1.8 [–0.4, 4.1], –13.2 [–17.9, –8.6], and –12.8 [–16.8, –8.9] for PBO, UPA15, and UPA30, respectively; sustained through wk48. Similar results were observed with FCP (mean [95% CI] change from induction BL: PBO 126 [–103, 356], UPA15 –2946 [–4121, –1772], UPA30 –1871 [–2577, –1165]). Severe adverse events (AEs) and serious AEs were lower with UPA treatment compared with PBO (Table 1). The rates of most AEs of special interest were similar between UPA and PBO; however, numerically higher rates of herpes zoster, adjudicated gastrointestinal perforations, neutropenia, lymphopenia, creatine phosphokinase elevation, and hepatic disorders were reported in pts treated with UPA vs PBO (Table 1). Conclusion In pts completing wk48 of the LTE, sustained efficacy was observed in clinical and endoscopic endpoints with over 2 years of UPA treatment, while maintaining an overall positive safety profile in pts with CD. Reference: 1. Loftus EV Jr, et al. N Engl J Med. 2023;388:1966–80

P845 Vedolizumab induces endoscopic healing uniformly irrespective of disease location: post-hoc analysis of the LOVE-CD trial

Abstract Background Vedolizumab (VDZ) is a gut-selective anti–α4β7-integrin monoclonal antibody approved for the treatment of Crohn's disease (CD). We performed a post-hoc analysis of the LOVE-CD trial to evaluate the effect of disease location on endoscopic healing. Methods LOVE-CD is a prospective multicentre study of VDZ therapy in adult patients with moderate-severe CD (Crohn's Disease Activity Index (CDAI) >220 and presence of ulcers at endoscopy). Patients received VDZ 300 mg infusions at weeks 0-2-6 followed by 8 weekly infusions up to week 52. An additional infusion at week 10 was given to patients without clinical response (CDAI decrease <70 points). Corticosteroids had to be withdrawn by week 26. Ileocolonoscopies were performed at weeks 0, 26, and 52, recorded, and centrally scored by 2 independent readers using the Simple Endoscopic Score for Crohn's Disease (SES-CD). The primary endpoint for this analysis was the proportion of patients, stratified by disease location (according to Montreal classification), with ulcer-free endoscopy (absence of any ulceration; SES-CD ulcer score 0) at week 52. Key secondary endpoints at week 52 were the proportion of patients, stratified by disease location, with endoscopic remission (SES-CD <4 for L2/L3 CD or <2 for L1 CD, and no subscores >1), with combined steroid-free clinical and endoscopic remission (CDAI<150 and endoscopic remission), the segmental healing rates, and ulcer healing rates stratified by disease duration. Results 186 patients were included in this intention to treat (ITT) analysis: 42 (22.6%) with L1, 52 (28.0%) with L2, and 92 (49.5%) with L3 disease. Baseline characteristics are shown in table 1. At week 52, the primary endpoint (absence of all ulcerations) was attained in 15/42 patients with L1 (35.7%), 20/52 with L2 (38.5%) and 25/92 with L3 CD (27.2%) (ITT, NRI (p=0.327)). Endoscopic remission was observed in 12/42 patients with L1 (28.6%), 20/52 with L2 (38.5%), and 29/92 with L3 disease (31.5%) (ITT, NRI (p=0.558)). The combined endpoint of clinical-endoscopic remission was reached in 9/42 L1 (21.4%), 16/52 L2 (30.8%), and 23/92 L3 patients (25.0%) (ITT, NRI (p=0.571)). Resolution of ileal ulcers was achieved in 15/40 L1 patients (37.5%) and 37/90 L3 patients (41.1%) (ITT, NRI (p=0.698)), resolution of colonic ulcers in 21/52 L2 (40.4%) and 45/90 L3 patients (50.0%) (ITT, NRI (p=0.268). Patients with early CD (disease duration <2 years) had higher ulcer healing rates than patients with late CD (47.5% versus 24.8%) (ITT, NRI (p=0.002)). Conclusion This post-hoc analysis of LOVE-CD shows that disease location does not affect endoscopic healing rates with VDZ in CD. However, early CD is associated with significantly higher endoscopic remission rates compared to late CD.

Safety and Effectiveness of Vedolizumab and Ustekinumab in Elderly Patients with Inflammatory Bowel Disease: A Real-Life Multicentric Cohort Study.

Data on ustekinumab and vedolizumab in the elderly inflammatory bowel disease (IBD) population are limited. The aim of the current study was to assess the safety and effectiveness of both in an elderly real-life population. A multicentric retrospective study was performed on IBD patients who started vedolizumab or ustekinumab between 2010 and 2020. Clinical and endoscopic remission rates and (serious) adverse events (AE) were assessed. A total of 911 IBD patients were included, with 171 (19%) aged above 60 (111 VDZ, 60 UST). Elderly patients treated with vedolizumab or ustekinumab had an increased risk for non-IBD hospitalization (10.5% vs. 5.7%, p = 0.021) and malignancy (2.3% vs. 0.5%, p = 0.045) compared to the younger population. Corticosteroid-free clinical (50% vs. 44%; p = 0.201) and endoscopic remission rates (47.9% vs. 31%, p = 0.07) at 1 year were similar. Comparing vedolizumab to ustekinumab in the elderly population, corticosteroid-free (47.9% vs. 31%, p = 0.061) and endoscopic remission rates (66.7% vs. 64.4%, p = 0.981) were similar. Vedolizumab- and ustekinumab-treated patients had comparable infection rates (13.5% vs. 10.0%, p = 0.504), IBD flare-ups (4.5% vs. 5%, p = 1.000), the occurrence of new EIMs (13.5% vs. 10%, p = 0.504), a risk of intestinal surgery (5.4% vs. 6.7%, p = 0.742), malignancy (1.8% vs. 3.3%, p = 0.613), hospitalization (9.9% vs. 11.7%, p = 0.721), and mortality (0.9% vs. 1.7%, p = 1.000). AE risk was associated only with corticosteroid use. Ustekinumab and vedolizumab show comparable effectiveness and safety in the elderly IBD population. Elderly IBD patients have an increased risk for non-IBD hospitalizations and malignancy compared to the younger IBD population, with corticosteroid use as the main risk factor.

Comprehensive systematic review and pooled analysis of real-world studies evaluating immunomodulator and biologic therapies for chronic pouchitis treatment.

Pouchitis is a common complication after restorative ileal pouch-anal anastomosis following proctocolectomy for ulcerative colitis. Antibiotic-dependent or antibiotic-refractory chronic pouchitis (CP), which is a common cause of pouch failure affecting 15-20% of patients, is challenging to treat. The efficacy of second-line immunomodulator and biologic therapy remains poorly defined. We present a pooled analysis of real-world efficacy data from peer-reviewed full-text manuscripts, focusing on immunomodulator and biologic therapies in CP. Embase and PubMed databases were searched for full-text articles describing the treatment of CP. We performed a systematic review and pooled analysis of published studies to assess the efficacy of immunomodulators, including thiopurines and methotrexate, and biologics including antitumor necrosis factor, anti-integrin, and interleukin-12/23 antagonists. Clinical and endoscopic response and remission rates were combined for pooled analyses. Rates of treatment discontinuation and safety were also assessed. Pooled analysis comprised 20 full-text articles (485 patients). Overall clinical response rate was 46% (95% CI: 35-59%) and clinical remission rate was 35% (95% CI: 21-52%). Overall endoscopic response and remission rates were 41% (95% CI: 18-68%) and 15% (95% CI: 5-39%), respectively. Individual agents' safety profile was reassuring, with vedolizumab being the most favorable. The real-world efficacy data of immunomodulators in the treatment of CP is insufficient. Vedolizumab and ustekinumab appeared effective and safe for CP, whereas anti-TNFs showed higher rates of adverse events. The high heterogeneity within the studies is attributed to the real-world study design, obfuscating drug efficacy comparisons across the studies. Further studies are required to define the comparative effectiveness of available treatments of CP.

Effectiveness and safety of upadacitinib for inflammatory bowel disease: A systematic review and meta-analysis of RCT and real-world observational studies

BackgroundUpadacitinib, a novel and selective inhibitor of Janus kinase 1, has demonstrated promising efficacy in managing inflammatory bowel disease (IBD). In this systematic review and meta-analysis, our primary aim was to comprehensively assess the therapeutic effectiveness and safety profile of upadacitinib in the treatment of patients with IBD. MethodsWe conducted an extensive literature search across prominent databases, including Medline, Embase, Web of Science, and Cochrane Central, to identify pertinent studies providing insights into the efficacy and safety of upadacitinib in IBD. The primary endpoint was the achievement of clinical remission, while secondary endpoints encompassed clinical response, endoscopic response, endoscopic remission, and the evaluation of adverse events (AEs). ResultsIn this meta-analysis of nine studies, we categorized results by study type. Clinical remission rates were: RCTs 36 % (95 % CI = 30–42 %), real-world studies 25 % (95 % CI = 1–49 %), retrospective studies 40 % (95 % CI = 24–56 %), cohort studies 55 % (95 % CI = 25–85 %). Clinical response rates were: RCTs 61 % (95 % CI = 55–67 %), real-world studies 42 % (95 % CI = 14–70 %), cohort studies 65 % (95 % CI = 57–73 %). Endoscopic remission rates were: RCTs 19 % (95 % CI = 15–24 %), cohort studies 29 % (95 % CI = 5–52 %). Endoscopic response rates were: RCTs 41 % (95 % CI = 36–47 %), cohort studies 57 % (95 % CI = 31–83 %). Incidence rate for any AEs: IBD 69 % (95 % CI = 63–76 %), UC 65 % (95 % CI = 57–74 %), CD 75 % (95 % CI = 67–82 %). ConclusionCumulative data from real-world studies and trials confirm the efficacy of upadacitinib in IBD induction and maintenance, with consistent safety. However, further long-term studies are needed to understand its sustained effectiveness and safety.

Correlation between Treatment Outcomes and Serum Vitamin D Levels As Well As Infliximab Trough Concentration among Chinese Patients with Crohn's Disease.

The relationship between vitamin D (vit-D) levels and the effectiveness of infliximab (IFX) in patients with Crohn's disease (CD) remains controversial. To evaluate the interaction between vit-D levels and the response to IFX therapy in patients with CD. This was a retrospective cohort study. Serum vit-D and IFX trough concentrations (TC) were measured in 84 patients, and statistical analyses were performed. The total vit-D deficiency rate at enrollment, at week 14 and week 38, was 64.3%, 41.67%, and 37.5%, respectively (P < 0.001). CD activity index (CDAI) (120, range, 93-142.75) and simplified endoscopic activity score for CD (SES-CD) (2, range, 0-4) at week 14 were lower than that of enrollment (CDAI, 136.5, range, 101.25-196; SES-CD 13, range, 5-23) (P < 0.001). The biochemical remission (BR), clinical remission (CR), endoscopic remission (ER), and response (ERe) rates of week 38 were 76.1%, 88.5%, 22.4%, and 67.2%, respectively. vit-D levels at enrollment were positively correlated with CDAI at week 38 (P = 0.024). IFX serum TC was related to BR (P = 0.036), CR (P = 0.032) at week 14, and ERe (P = 0.009) at week 38. Among Chinese patients with CD, vit-D levels prior to IFX therapy are related to CDAI scores, and IFX serum TC is associated with BR, CR, and ERe.

Dietary Interventions in Ulcerative Colitis: A Systematic Review of the Evidence with Meta-Analysis.

(1) Background: Ulcerative colitis (UC) is a chronic colon inflammation caused by genetic and environmental factors, including diet. This systematic review and meta-analysis aims to assess the impact of diet on UC management in children and adults (2) Methods: A comprehensive search across databases yielded relevant studies, and risk of bias in randomized controlled trials (RCTs) was assessed using the Cochrane Risk of Bias tool. This study was conducted in conformity to the 2020 PRISMA guidelines. The certainty of evidence for outcomes was evaluated using GRADE methodology. Meta-analysis was performed using Review Manager software version 5.4. (3) Results: Fourteen RCTs were included, results indicated higher clinical response, remission, and endoscopic remission rates in diet-treated groups. Carrageenan-free, anti-inflammatory, and cow milk protein elimination diets showed no significant advantages in maintaining clinical remission. However, a study involving fermented cow milk with bifidobacterial demonstrated favorable outcomes. Overall, pooled analysis leaned in favor of dietary intervention for sustaining clinical remission; (4) Conclusions: The relationship between diet and UC is an evolving terrain that demands deeper exploration. This systematic review and meta-analysis highlight the evolving relationship between diet and UC, necessitating further exploration. While understanding grows, adopting personalized dietary approaches could alleviate symptoms, and support a more positive disease trajectory.

Vedolizumab, Adalimumab, and Methotrexate Combination Therapy in Crohn’s Disease (EXPLORER)

Although biologics have revolutionized the treatment of Crohn's disease (CD), an efficacy ceiling has been reached. Combining biologic therapies may improve remission rates. EXPLORER, a phase 4, single-arm, open-label study, evaluated triple combination therapy with vedolizumab (300 mg on day 1, weeks 2 and 6, and then every 8 weeks), adalimumab (160 mg on day 2, 80 mg at week 2, then 40 mg every 2 weeks), and methotrexate (15 mg weekly) in biologic-naïve patients with newly diagnosed, moderate- to high-risk CD. Endoscopic remission at week 26 (primary end point; Simple Endoscopic Score for CD ≤2), clinical remission at weeks 10 and 26 (secondary end point; Crohn's Disease Activity Index <150), and incidences of adverse events and serious adverse events were evaluated. Among 55 enrolled patients, the mean CD duration was 0.4 years, the mean baseline Simple Endoscopic Score for CD was 12.6, and the mean baseline Crohn's Disease Activity Index was 265.5. At week 26, 19 patients (34.5%) were in endoscopic remission. At weeks 10 and 26, 34 (61.8%) and 30 patients (54.5%), respectively, were in clinical remission. Post hoc Bayesian analysis showed that the probabilities that triple combination therapy produced a higher endoscopic remission rate (33.5%; 95% credible interval, 22.4-45.7) than placebo (14%), vedolizumab monotherapy (27%), or adalimumab monotherapy (30%) were 99.9% or higher, 86.3%, and 71.4%, respectively. Six patients had serious adverse events. Combination therapy resulted in endoscopic and clinical remission at week 26 in 34.5% and 54.5% of patients, respectively, with no safety signal related to the treatment regimen. This supports further evaluation of combination therapy in CD. gov number: NCT02764762.

Efficacy of Combined Initial Treatment of Methotrexate with Infliximab in Pediatric Crohn's Disease: A Pilot Study.

The combination of antitumor necrosis factor-alpha (TNF-α) agents with immunomodulators (IMMs) is a common treatment for pediatric Crohn's disease (CD). Although methotrexate (MTX) can be a first-line medication as an IMM, most clinicians in real-life practice, especially in South Korea, are more familiar with thiopurines. This study aimed to compare the efficacy and immunogenicity of MTX and azathioprine (AZA) as concurrent therapies for pediatric CD. In this pilot study, 29 newly diagnosed pediatric patients with moderate-to-severe CD were randomized to receive either MTX (n = 15) (15 mg/body surface area (BSA) per week) or oral AZA (n = 14) (0.5 mg/kg per day) in combination with Infliximab (IFX). The primary outcomes were the proportion of patients in endoscopic, biochemical, and transmural remission after 14 and 54 weeks of IFX therapy. The trough levels (TLs) of IFX and anti-drug antibody (ADA) levels were also compared. Among the 29 patients, there were no significant differences in the biochemical (p = 1.0 at week 14, p = 0.45 at week 54), endoscopic (p = 0.968 at week 14, p = 0.05 at week 54), or transmural (p = 0.103 at week 54) remission rates between the two medications during the concurrent therapy. Additionally, the trends in the IFX trough and ADA levels over time during the treatments were similar for both medications, with no significant differences (p = 0.686, p = 0.389, respectively). The MTX showed comparable efficacy to the AZA in pediatric CD patients with moderate-to-severe disease. This effectively maintained adequate IFX levels and reduced ADA production. Therefore, although additional large-scale clinical trials are needed, this study demonstrated that either MTX or AZA can be selected as IMMs in the concurrent treatment of pediatric CD, depending on individual medical institutions' circumstances.