Colectomy Rates Research Articles

Effectiveness of Upadacitinib for Patients With Acute Severe Ulcerative Colitis: A Multicenter Experience.

A significant proportion of patients with acute severe ulcerative colitis (ASUC) require colectomy. Patients with ASUC treated with upadacitinib and intravenous corticosteroids at 5 hospitals are presented. The primary outcome was 90-day colectomy rate. Secondary outcomes included frequency of steroid-free clinical remission, adverse events, and all-cause readmissions. Of the 25 patients with ASUC treated with upadacitinib, 6 (24%) patients underwent colectomy, 15 (83%) of the 18 patients with available data and who did not undergo colectomy experienced steroid-free clinical remission (1 patient did not have complete data), 1 (4%) patient experienced a venous thromboembolic event, while 5 (20%) patients were readmitted. Upadacitinib along with intravenous corticosteroids may be an effective treatment for ASUC.

BREASTFEEDING STATUS AND DISEASE SEVERITY IN PEDIATRIC PATIENTS WITH ULCERATIVE COLITIS: AN EXPLORATORY RETROSPECTIVE COHORT STUDY

Abstract OBJECTIVE While the protective effect of being breastfed on the development of ulcerative colitis has been well established, it is not known if being breastfed decreases colectomy rate and disease severity for pediatric patients. This work is designed to better understand the connection between breastfeeding status and disease severity of ulcerative colitis among pediatric patients. METHODS This exploratory retrospective cohort study analyzed the clinical and laboratory data of patients at Boston Children’s Hospital enrolled in a data registry and biorepository since 2012. Data was collected from charts and analyzed to determine if there is a significant difference in colectomy rate, pediatric ulcerative colitis activity index (PUCAI) score, ESR, or CRP, between not breastfed (n=56), breastfed (n=39), and mixed breastfed patients (n=31). Breastfed patients are defined as patients who were exclusively breastfed for greater than or equal to three months. Patients who were never breastfed were considered not breastfed. Patients who were exclusively breastfed for less than three months or received a mix of formula and breastfeeding were considered mixed breastfed. Statistical analysis of the groups was performed using a one-way ANOVA. RESULTS At disease diagnosis, the average PUCAI score of the not breastfed group (32.4) was significantly higher than the exclusively breastfed group (18.4) (p value = 0.0189). No significant difference was detected in the average PUCAI score of the mixed breastfed group (34.1) compared to the not breastfed group (32.4). Significant differences in the colectomy rate between all three groups were not detected, and likewise we did not find significant differences in markers of disease severity including ESR, CRP, and hemoglobin at diagnostic visit between groups. CONCLUSION These results suggest that children with ulcerative colitis who were exclusively breastfed have a lower average PUCAI score at the time of diagnosis than those who were not breastfed. Further investigation with larger data sets may be necessary to determine other benefits of exclusive breastfeeding in pediatric ulcerative colitis patients.

LOWER MORTALITY RISK WITH COMBINATION THERAPY WITH ANTI-TNF THERAPY AND THRIOPURINE COMPARED TO THIOPURINE ALONE IN ELDERLY PATIENTS WITH UC

Abstract INTRODUCTION Despite increasing incidence rates of ulcerative colitis (UC) in the elderly, efficacy and safety data for medical management in this cohort is lacking due to underrepresentation in clinical trials and registries. Selection of medical therapy is often complex, taking into consideration a multitude of factors, including real and perceived risks of infection and malignancy. In the past, immunomodulators, such as thiopurines, were commonly used as monotherapy for maintenance, offering the added advantages of affordability and oral administration. Indeed, there are elderly patients who have been maintained for decades on thiopurine monotherapy. Further, thiopurines can be used in combination with anti-TNF therapy for improved efficacy and reduced immunogenicity compared to monotherapy with either agent in ulcerative colitis (UC). Whether the use of combination therapy imposes an additive risk compared to thiopurine monotherapy is still unclear. This study aimed to investigate outcomes of thiopurine monotherapy versus combination therapy with anti-TNF agents in elderly patients (age ≥65 years) with UC. METHODS The TriNetX Research Network was accessed on October 15th, 2023, to compare outcomes in elderly patients 65 years or older with UC who are receiving thiopurine monotherapy and patients who are receiving combination therapy with an anti-TNF (adalimumab, certolizumab pegol, golimumab, or infliximab). The outcomes examined were 1-year rate of corticosteroid and colectomy as well as 10-year rate of mortality, colon cancer, skin cancer, and respiratory and urinary tract infections. Statistical risk analysis was performed using the TriNetX analytical platform. RESULTS A total of 2,597 patients (2,245 thiopurines monotherapy and 352 AZA plus anti-TNF combination therapy) were included in the study (Table 1). Among the monotherapy and combination therapy cohorts, mean age was 71 years old and approximately 56% male. Ten-year mortality was higher in the thiopurine monotherapy group (OR 1.67, p=0.002). The combination therapy cohort had higher rates of steroid use (32.4% vs. 24.3%, p=0.001) and colectomy at 1 year compared to the monotherapy cohort (4.5% vs. 1.2%, p<0.001). There was no significant difference in 10-year risk of colon cancer (OR 1.05, p=0.88), skin cancer (OR 1.51, p=0.06), incidence of respiratory (OR 1.48, p=0.07) and urinary tract infections (OR 1.18, p=0.23). CONCLUSION The study findings highlight the risks of thiopurine use in patients over the age of 65 given the significantly higher 10-year mortality risk in thiopurine monotherapy-treated patients. The results also suggest that combination therapy with thiopurine and anti-TNF therapies - despite utilization in patients with more active disease indicators - is not associated with an additive risk in terms of infection and mortality in elderly patients. Table 1 Characteristics and Outcomes of Elderly Patients with UC either on Thiopurine Monotherapy or Combination Therapy with anti-TNF agents

UPADACITINIB AS SECOND- AND THIRD-LINE SALVAGE THERAPY FOR REFRACTORY ACUTE SEVERE ULCERATIVE COLITIS

Abstract INTRODUCTION Intravenous (IV) corticosteroids (CS) remain first line therapy for acute severe ulcerative colitis (ASUC). Up to 40% are CS refractory. Prior biologic exposure, colonic drug loss and systemic toxicities limit their utility. Colectomy rates remain up to 30% in CS refractory cases emphasizing the need for expanding alternative strategies. We report our experience of upadacitinib (UPA) as 2nd and 3rd line salvage in refractory ASUC. METHODS ASUC was defined by Truelove and Witts’ criteria. Travis index was used to assess 3-day response to inpatient (IP) therapies. IP therapeutic non-response was defined as ≥ 8 bowel movements (BM)/day or > 2 BM and CRP > 45 mg/L. IP response was defined as ≤ 4 BM and CRP < 45 mg/L. Primary outcome include response to IP UPA salvage at day 3 and colectomy by week (WK) 16. Patients (pts) undergoing colectomy were followed until time to event. Secondary outcomes include post-discharge clinical and biochemical remission, clinical response and rate of adverse events at WK 8/16. Clinical remission/response was defined by STRIDE-2 guidelines using partial mayo (PM). Biochemical remission was defined as fecal calprotectin (FC) <250 ug/g or CRP <5 mg/L. No cardiovascular, thromboembolic or non-HSV infections were seen. RESULTS Four ASUC pts failing IV CS required inpatient UPA salvage (Table 1). At baseline, all pts had severe pancolonic endoscopic disease (median total mayo 11, median PM 9). Median exposure to prior advanced therapies was 4. Baseline median FC was 3000 ug/g and CRP 167 mg/dL. Pt #1, #2 received UPA as 2nd line salvage due to prior IFX failure (Table 2). Pts #3, #4 received UPA as 3rd line salvage due to IFX failure at index admission (IA). One received UPA 45 mg QD (pt #1) and three received 30 mg BID (pts #2-4). All pts achieved IP response to UPA. No pts needed colectomy at IA. Overall median length of hospital stay was 14 days. Median time to UPA response was 2.5 days. Discharge time post-UPA was 3.5 days. At WK 8, pt #1 attained response with resolution of rectal bleeding (RB), BM (-85%), CRP (-91%), FC (-82%), and PM 3 (Table 3-4). At WK 16, pt #1 met criteria for clinical and biochemical remission with PM 1, normal FC (-95%) and CRP (-98%). Pt #1,#3 achieved complete steroid taper and avoided colectomy over 16 WK. Pt #2 failed CS taper and had colectomy on day 33. Pt #3 achieved clinical and biochemical remission with PM 1 and CRP 5 mg/dL (-94%) at WK 8. At WK 16, pt #3 sustained CS free clinical and biochemical remission with normalized BM (-93%), FC (-92%), CRP (-98%) and sustained resolution of RB. Assessment of pt #4 was limited to IP UPA response pending follow up. Outcomes were similar in pts receiving UPA as 2nd and 3rd line salvage. CONCLUSION We report efficacy and safety of UPA as 2nd and 3rd line salvage for ASUC thus expanding the armamentarium for medical salvage therapy. Table 1 Baseline Disease Characteristics Table 2 Patient Specific Inpatient Therapy Table 3 Comparison of Disease Activity Parameters at Baseline, Discharge, 8 Weeks and 16 Weeks Table 4 Percentage Difference of Disease Activity Parameters at Discharge, 8 Weeks and 16 Weeks in Comparison to Baseline

P782 Comparison of accelerated and standard infliximab induction regimens in Acute Severe Ulcerative Colitis using propensity score: A retrospective multicenter study in a Chinese cohort

Abstract Background The optimal regimen of infliximab salvage in acute severe ulcerative colitis (ASUC) patients remains controversial. This retrospective multicenter study aimed to compare accelerated and standard infliximab induction in a Chinese cohort of ASUC patients, and to explore risk factors associated with poor prognosis. Methods Data were collected retrospectively from steroid-refractory ASUC patients who received infliximab induction as rescue therapy at seven tertiary centers across China. Accelerated infliximab induction was defined as receiving two doses of infliximab on or before day 13 and/or receiving intensified doses of ≥ 7.5 mg/kg. Outcomes including colectomy and clinical remission (Mayo score ≤ 2 and every subscore ≤ 1 at day 14) rates were compared using propensity score adjustment for potential confounders. The variables in propensity score model was determined by logistic regression analysis for accelerated induction. Results A total of 76 patients were included: 29 received standard induction and 47 received accelerated induction. The overall disease severity was significantly higher in patients of accelerated group (Table). The 30-day colectomy rates did not differ between two groups (4.3% vs. 0%, P=0.522). However, the accelerated group had a higher 90-day colectomy rate (17.8% vs. 0%, P=0.019) and lower clinical remission rate (27.7% vs. 65.5%, P=0.001). (Figure. A) After adjusting with propensity score and institution, there was no significant difference in colectomy (P=0.20) or no clinical remission (P=0.48) hazards. Dose-effect curves plotted by restricted cubic splines (adjusted for propensity score and institution) showed decreased colectomy hazard with higher cumulative infliximab dosage within 5 days, while no improvement was observed for increasing cumulative infliximab dosage within 28 days. (Figure. B) Multivariate logistic regression analyses revealed female gender (OR=7.69, 95%CI: 1.96-33.33) and C-reactive protein (CRP) >10 mg/L at infliximab initiation (OR=5.00, 95%CI: 1.27-24.34) as independent risk factors for no clinical remission. (Figure. C) Conclusion After adjusting for confounders, there were no significant differences in colectomy or clinical remission rates between accelerated and standard infliximab induction among steroid-refractory ASUC patients. Elevated CRP at infliximab initiation indicated more intensive treatment or earlier surgery to be considered. And it would be better to give early intensified dosage within 5 days if needed.

P635 Intravenous albumin infusion does not augment the response rate to a combination of exclusive enteral nutrition and intravenous steroids in Acute Severe Ulcerative Colitis: a randomized controlled trial

Abstract Background 30-40% patients with acute severe ulcerative colitis (ASUC) fail intravenous (IV) steroids requiring medical rescue therapy/colectomy. Low baseline albumin predicts steroid non-response, and exclusive enteral nutrition (EEN) has been shown to improve steroid response and albumin levels. Albumin infusion due to its anti-inflammatory and anti-oxidant properties can further improve steroid response in ASUC, which was evaluated in present study. Methods In this open-label randomized controlled trial, patients with ASUC were randomized in 1:1 ratio to albumin + SOC + EEN vs. SOC + EEN (Jan2021 – Feb2023). Both arms received 5 days of EEN with 400 mg IV hydrocortisone/day. Patients in albumin arm were administered 5 days of 20% w/v intravenous albumin (100 ml). Primary outcome was steroid failure (need for rescue medical therapy or colectomy) and proportion of patients with adverse events. Results Sixty-one patients (albumin-30, SOC-31) (mean age-31.6 ± 10.4 years, male- 57.4%), were included. Baseline characteristics were comparable. There was no difference in steroid failure between albumin and SOC arm (10/30 (33.33 %) vs 13/31 (41.94 %), p=0.49). No adverse events were reported with albumin infusions. Colectomy rate (10 % vs 9.68 %, P=1), response to salvage medical therapy (88.89 % vs 76.92 %, P=0.62) and median duration of hospitalization (10.5 (7-16) vs 10 (7-20), P=0.43) were also comparable. Long-term composite outcome of colectomy and re-admission rates was numerically higher in the albumin than SOC arm (37.04 % vs 17.86 %), although it did not reach statistical significance. Conclusion There was no benefit of intravenous albumin infusion as an adjunct to IV steroids and EEN in patients with ASUC.

P822 Therapeutic Management And Risk Of Colectomy In Patients With Acute Severe Ulcerative Colitis And Previous Exposure To Anti-Tnf Drugs. A Cohort Study Of Geteccu

Abstract Background There are few data regarding the management on acute severe ulcerative colitis (ASUC) flare in patients with previous anti-TNF exposure. We evaluated the medical management, the risk of colectomy and factors associated comparing with a bionaive cohort. Methods A retrospective and multicentric study of GETECCU. Patients with ASUC episode between 2010-2020 were included in two cohorts: bio-exposed (cohort 1) and bio-naive (cohort 2). Patients with previous other biologics or JAK inhibitors exposure were excluded. Steroid response was defined as reduction of bowel movements and C Reactive Protein (CRP). Rescue therapy was used after steroid failure and maintenance therapy after steroid or rescue therapy response/remission. Clinical effectiveness of rescue and maintenance therapy was analyzed using partial mayo score (clinical response with decreased of 2-3 points, clinical remission ≤2). Colectomy rate was evaluated at short and long-term using survival analysis and was compared using cox logistic regression. Results Finally, 461 patients were included from 33 centres. Basal characteristics and medical management are shown in Table 1. Bioexposed patients received steroid therapy less frequently (82 vs 97%, p 0.001). Comparing with bionaive cohort, there were differences between medical management although steroid response and the use of rescue therapy were similar. However, clinical remission at one year was lower (44 vs 59%, p 0.03). Colectomy rates at 1 and 12 months were of 15 and 17% in Cohort 1, respectively. Comparing with bionaive cohort, there were a higher risk of colectomy at short and long-term, HR 2.46 (1.57-3.87, p 0.001) (Figure 1). There were no factors associated with colectomy at one year. Response to steroids was the only protective factor of colectomy at one year (RR 0.17, 0.07-0.45, p 0.001). Conclusion Management of ASUC in bio-exposed patients is heterogeneus and differs from bionaive patients. The risk of colectomy is increased. Although the response to medical treatment is not negligible, special efforts in standardizing therapies are warranted in order to improve prognosis.

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.

P972 Short and long-term outcomes after acute severe ulcerative colitis in children: A Canadian single centre experience

Abstract Background The short and long-term course of ulcerative colitis (UC) following an episode of acute severe UC (ASUC) in children is insufficiently characterized. We aimed to assess contemporary outcomes in children hospitalized with ASUC. Methods This was a retrospective cohort study of children aged 2-17 years hospitalized with ASUC between 2010 and 2022 at a tertiary center in London, Ontario, Canada. All data were recorded using standardised Case Report Forms, de-identified, and entered into a central database registry using Research Electronic Data Capture (REDCap) Steroid non-response was defined as requirement of medical rescue therapy or colectomy. Results A total of 58 children hospitalized with ASUC were included (male: 55.2% [n =32], mean age at admission: 12.2 ± 3.5 years). The majority had extensive colitis (82.4% [n = 42]) at the time of diagnosis. 74% (n = 43) presented within one year of symptom onset and 31% (n = 18) had ASUC as their index presentation with UC. 15.5% (n = 9) of patients had prior purine analogues and 20.7% (n = 12) had received biologics prior to ASUC presentation. Median Pediatric Ulcerative Colitis Activity Index (PUCAI) score on admission was 65.0 (IQR: 60.0 – 75.0). After intravenous corticosteroid therapy 68.9% (n = 40) responded to steroids. Of the patients with steroid non-response (31% [n = 18]), 3.4% (2/58) underwent colectomy and 27.6% (16/58) patients received infliximab rescue therapy. Median PUCAI score was significantly lower on day 3 between steroid responders and steroid non-responders (37.5 vs 60, p <0.01). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 7.4% (4/54) and 8% (4/50) respectively. Short term and long-term hospitalization rates for UC exacerbation following discharge was 25.9% (14/54) and 16% (8/50) respectively. Similar rates of long-term colectomy and hospitalizations were observed between steroid responders and non-responders. On univariate analysis, no statistically significant factors associated with steroid non-response were identified. Conclusion 17% of patients hospitalized for ASUC required colectomy within 12 months of presentation. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates are still high. Future research should focus on earlier identification and treatment of children at high risk of exacerbation to prevent complications.

P941 Observational study of tofacitinib in ulcerative colitis in Sweden (ODEN) – Interim analysis of clinical and biomarker data

Abstract Background Tofacitinib is a Janus kinase (JAK) inhibitor for the treatment of moderate to severe ulcerative colitis (UC). ODEN is an ongoing Swedish multicentre prospective observational study regarding effectiveness of tofacitinib in UC. In this interim analysis, we aimed to assess the clinical outcomes during the first 16 weeks. Methods Patients with active UC were enrolled 2020-2023 when starting tofacitinib as per clinical indication. Inclusion criteria were fecal (F) calprotectin >250 mg/kg or Mayo endoscopic score ≥2. Data were collected using an electronic case report form linked to the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG). Data concerning inflammatory markers, endoscopic activity, partial (p) Mayo, extra intestinal manifestations, health-related quality of life measures, corticosteroid use, and colectomy rates were collected regardless of tofacitinib discontinuation. Information collected at week 8 and 16 is presented here. Intention-to-treat (ITT) analysis was applied and tofacitinib discontinuation was considered as treatment failure (i.e., no tofacitinib-induced clinical or laboratory response or remission). McNemar’s test was used for proportion differences. Results The proportion of patients who previously had failed at least one biologic was 95% and at least two biologics, 62%. At inclusion, median p-Mayo was 5 and 39% of patients were on corticosteroids (Table 1a). Patients’ survival on drug is shown in Figure 1a. At week 8 and 16, 42% and 43%, respectively, achieved corticosteroid free clinical remission, Figure 1b. A 50% reduction in F-calprotectin was seen in 54% and 49% at week 8 and 16, respectively. The endpoint of Mayo endoscopic score 0 and/or F-calprotectin <100 mg/kg was achieved by 30% and 38% at week 8 and 16, respectively. Arthralgia frequency decreased significantly from baseline from 29% at inclusion to 13% and 11% at week 8 and 16 respectively. Three patients underwent colectomy the first 16 weeks (Table 1b). Conclusion After 16 weeks of treatment with tofacitinib, a substantial proportion of previously treatment refractory UC patients were in clinical and endoscopic corticosteroid-free remission, and a distinct improvement in F-calprotectin levels was observed. In addition, a significant reduction in arthralgia was noted.

P891 Comparative Effectiveness and Safety of Infliximab and Tacrolimus in the Treatment of Acute Severe Ulcerative Colitis

Abstract Background Acute severe ulcerative colitis (ASUC) affects approximately 20% of patients with ulcerative colitis (UC). Patients failing initial corticosteroid therapy receive salvage therapy with either infliximab (IFX) or calcineurin inhibitors, cyclosporine (CYS) or tacrolimus (TAC). We aimed to compare the effectiveness and safety of IFX and the oral calcineurin inhibitor, TAC, in this setting. Methods This retrospective cohort study included consecutive patients with ASUC, based on the Truelove and Witts criteria, admitted to Tel Aviv Medical Center between 2017 and 2022 and treated with salvage therapy. Demographic, clinical, and laboratory data were retrieved. The primary endpoint was successful salvage therapy defined as clinical response resulting in discharge without colectomy. Secondary endpoints included the colectomy rates at 90 days and the safety profile of the treatments. Results During the study period 96 patients with ASUC were admitted to our center. Of these, 40 patients received salvage therapy – 21 patients received IFX and 16 received TAC and were included in the analysis; 3 patients received CYS and were excluded from the study. Demographic data are detailed in Table 1. Disease duration was significantly longer in patients receiving TAC (mean (±SD) 9.7 years (±7.1) vs 4.5 (±5.9), p=0.04). In addition, patients receiving TAC had significantly greater prior exposure to advanced therapies (14 (87.5%) vs 6 (28.6%), p<0.001) and 12 (75%) patients had previous exposure to IFX. Baseline markers of disease severity including disease extent, hemoglobin, C-reactive protein (CRP), albumin and body mass index (BMI) were similar between the treatment groups (Table 1). Therapeutic success was similar between treatment groups (IFX: 18 (86%) vs TAC: 15 (94%), p=0.62). The 90-day colectomy rate (IFX: 4 (19%) vs TAC: 2 (12.5%), p=0.68), CRP upon discharge (median (IQR) IFX: 15 mg/L (3.3-27) vs TAC: 11 mg/L (5.4-25, p=0.64) and length of hospitalization (mean (±SD) IFX: 23.5 days (±19.46) vs TAC: 17.56 days (±5), p=0.19) were similar between the groups. Safety profiles were similar between the treatment groups with mild electrolyte disturbances treated conservatively in both groups and no observed infections, deaths or other adverse events. Conclusion This real world, retrospective study shows that IFX and TAC have similar effectiveness and safety in the setting of ASUC. In this study, patients receiving TAC had significantly longer disease duration and advanced therapy exposure than those receiving IFX and still maintained excellent effectiveness highlighting TAC’s value in this setting.

P347 A Trend Analysis of Inflammatory Bowel Disease in Non-Endemic Era (1993-2023)

Abstract Background In this study, we aimed to evaluate the demographic and epidemiological trends of Ulcerative Colitis (UC) and Crohn’s Disease (CD) in non-endemic era for inflammatory bowel disease (IBD) during the past three decades. Methods UC and CD patients who had follow-up at least 6 months between June 1993 and February 2023 were evaluated retrospectively. Electronic medical databases, personal queries and IBD registries have all been used to collection data on the clinical and demographic characteristic of all patients. Results A total of 1549 adult patients with UC and CD were admitted to study. UC was diagnosed in 873 (56.4%) patients (Male 538, 61.6%) and CD was diagnosed in 676 (43.6%) patients (Male 404, 59.8%). The median follow-up duration was 8.3 years for UC patients and 6.8 years for CD patients. In patients with UC, proctitis was 154 (17.6%), left sided colitis was 410 (47%) and extensive colitis was 309 (35.4%). In CD patients, ileal involvement was found in 297 (43.9%), colonic in 76 (11.2%), ileo-colonic in 299 (44.2%) and isolated upper GI involvement in 4 (0.6%) cases. 529 (78.3%) patients had non-stenosing non-penetrating behavior, 45 (6.7%) had stenosing behavior, 102 (15.1%) had penetrating behavior, as well as 196 (29%) patients had perianal disease. Mesalazine 658 (75.4%) and thiopurine 397 (45.5%) were the most frequently used conventional treatments for UC, while thiopurine 304 (45%) was most commonly used for CD patients. In the last two-decade, proportion of the biologic usage were 27.9% and 32.1% in UC patients 28.5% and 31.4% in CD patients respectively. Over the three decades, abdominal surgery was 49.2%, 27.8% and 36.3% in CD and colectomy rates was 2.0%, 2.7% and 3.7% in UC patients. While the rate of UC patients has slightly decreased to 98 (61.6%), 401 (58.5%) and 374 (53%) frequency of CD patients has increased to 61 (38.4%), 284 (41.5%) and 331 (47%). Over the course of three decades, there were more UC patients than CD patients, however proportion of UC/CD has been continuously decreased (1.61, 1.41 and 1.13) for three decades respectively. Conclusion Our study showed that the frequency of UC and CD has significantly increased during the previous three decades in non-endemic era for IBD. While the frequency of UC patients has slightly decreased, that of CD patients has steadily increased over the past three decades. Although the use of biologics has significantly increased, proportions of the abdominal surgeries and colectomies has not prominently changed.

P1057 Upadacitinib as Salvage Therapy for Acute Severe Ulcerative Colitis: A Single-Center Experience

Abstract Background Ulcerative colitis (UC) often leads to hospitalization and may be resistant to standard treatments, necessitating colectomy. Upadacitinib (UPA), an oral selective Janus kinase 1 inhibitor, offers a novel mechanism and the benefit of rapid and predictable pharmacokinetics which suggest it may be efficacious in acute severe UC (ASUC). However, there are a limited number of cases using different dosing regimens describing the potential of this treatment for ASUC. We describe the efficacy and safety of UPA in hospitalized patients with ASUC at our center. Methods We conducted an observational cohort study of patients hospitalized for ASUC treated with UPA 45 mg/d as a rescue therapy after failure or incomplete response to other therapies, including corticosteroids. Patient demographics, disease characteristics, and clinical data were collected. The Simple Clinical Colitis Activity Index (SCCAI) was used to monitor clinical response. Clinical outcomes, including loss of response and colectomy, were collected. Results Ten patients (ages 21-78, 40% female) hospitalized for ASUC were treated with UPA (population characteristics and clinical summarized in Table 1). The majority of patients (8/10) had prior exposure to two or more advanced therapies. The median SCCAI score at the time of UPA initiation was 8.5, with improvement in five patients on upadacitinib at week 2 (Figure 1). Six of 10 patients discontinued UPA, 3 of whom underwent colectomy during the same hospitalization due to inadequate response. Two patients underwent surgical intervention after discharge from the hospital. Patients who underwent colectomy had a significantly lower albumin level at the time of UPA initiation compared to patients who didn’t undergo colectomy (3.0 and 4.2 g/dL, respectively; p = 0.005), but not CRP (28.5 and 29.8 mg/L, respectively; p = 0.48). One patient had discontinuation of upadacitinib during the induction phase due to elevated liver enzymes. The median time to discontinuation was 7.5 days. Of the 4 patients on ongoing therapy with UPA after initiation in hospital, 2 have been on the maintenance dose for over 6 months with ongoing remission. Conclusion Our experience with UPA 45 mg/d for salvage therapy in ASUC patients demonstrated a higher colectomy rate than reported in earlier studies, which . Although some patients benefited from UPA with an improvement in SCCAI scores by week 2, the colectomy rate highlights the need for further research to identify which patients are most likely to benefit from UPA therapy. Our findings underscore the importance of personalized approaches to ASUC treatment and warrant further investigation in larger, controlled studies.

P1001 Predictive factors of colectomy in patients admitted with Acute Severe Ulcerative Colitis

Abstract Background Acute severe ulcerative colitis (ASUC) is a life-threatening condition which requires quick decision making and urgent treatment. To facilitate this process, it is essential to identify patients at a high risk of emergency colectomy. The aim of this study is to identify predictors for emergency colectomy in patients with ASUC. Methods A retrospective study of 121 patients admitted with ASUC to a single gastroenterology centre between 2010 and 2020 was performed. Clinical and demographic data, laboratory and endoscopic examinations results were analysed as potential predictors of colectomy. Albumin and C-reactive protein (CRP) levels were recorded at baseline and at the 3rd day after intravenous steroids (IVS) initiation. Results 119 patients initially received IVS, while 2 patients with suspected intestinal perforation underwent emergency colectomy on the first day. 64 (53%) were women, with a median age of all patients of 33 (IQR 27-49) yrs. 15 (12.4%) patients admitted with ASUC underwent colectomy, while mortality rate during hospitalization was 1.7%. During the entire follow-up period, with a median duration of 46.5 months (23-88.25), colectomy was performed in 19 (15.7%) patients. Overall, in the study group, colectomy rate at 1 month, 3 months and 2 years were 12.4%, 12.4%, and 14.0%, respectively. Assessing further outcomes after colectomy, during the follow-up period, 13 (68.4%) achieved clinical remission, 1 died during the operation, and 5 (26.3%) patients still have an active course of the disease requiring immunosuppressive treatment. When comparing patients in the colectomy group (n=13) with patients who avoided colectomy during this hospitalization (n=105), no significant differences were found in age, sex, duration of illness, body mass index, endoscopic activity, the use of prednisolone or azathioprine prior to admission or previous treatment with biologics. The presence of cytomegalovirus and Clostridium difficile infection was also not associated with a higher risk of colectomy. Significant differences between the groups were found comparing the laboratory findings: the strongest predictor of colectomy was the CRP/albumin ratio at day 3 after IVS initiation (median value was 1.26 (0,81-3,26) in colectomy group vs. 0,64 (0,25-1,36) in non-colectomy group, p<0.001). The difference was also observed when comparing albumin (median 26 (24-28) vs. 29 (27-32), p=0.012) and CRP (median 33 (25-83) vs. 16 (8-37), p=0.003) levels separately on the 3rd day, while at baseline there was no significant differences in laboratory findings. Conclusion A low serum albumin level, higher CRP and CRP/albumin ratio are predictive factors of emergency colectomy in ASUC patients.

P356 Long-term outcome of UC patients in clinical remission with different level of mucosal activity: real world, retrospective, multicontinental study

Abstract Background In contrast to the increasingly rigorous endpoints of clinical trials of ulcerative colitis (UC), Mayo endoscopic score (MES) ≤ 1 is mostly set as target during clinical follow-up, but long-term outcomes may differ according to different level of healing. Therefore, our study aimed to compare the long-term outcomes of UC patients in clinical remission with different MES and UCEIS scores in real-life condition. Methods UC patients in clinical remission (defined by pMayo<2 with no rectal bleeding) who underwent colonoscopy between 2016-2020 were consecutively enrolled in this multicenter retrospective study. Mayo and UCEIS endoscopic scores were evaluated and clinical and demographic data were collected at baseline. Clinical flare, colectomy, hospitalization and treatment modifications were recorded during at least 3 year of follow-up. Primary outcome was the clinical flare, while secondary outcomes were hospitalization, colectomy, new biological initiation and biological dose escalation during follow-up. Outcomes were compared with Log-rank test and survival characteristics were plotted. Results In total, 156 UC patients were enrolled with a median age of 46.0 (IQR 35.5-58.0), while male/female ratio was 49.4 % (Table 1.). Near to half of the patients (44.9%) had MES>0 endoscopic activity at baseline. Non zero baseline MES (Figure 1.; p = 0.002; MES 0 vs 1 p = 0.004) and UCEIS (p < 0.001; UCEIS 0 vs. 1 p = 0.016) scores were associated with higher rate of clinical flare. Higher baseline MES (p = 0.042) and UCEIS (p = 0.008) scores were coupled with increased risk of hospitalization. Colectomy rates were low. Increased baseline UCEIS (p = 0.003), but not MES score was coupled with new biological treatment initiation, while only UCEIS score was associated with biological treatment intensification (>4; p = 0.008). Conclusion Our study suggests differentiating between complete MH from MES 1 as long-term outcomes were more favorable in case of lower endoscopic scores. Consequently, targeting complete MH should be considered to achieve deep remission and disease clearance.

P550 Short and long-term outcomes after acute severe ulcerative colitis in adults: A 12 year Canadian experience in the post biologic era

Abstract Background Patients with acute severe ulcerative colitis (ASUC) are at increased risk of colectomy following an episode of acute severe exacerbation. Medical rescue therapy in steroid non-responders has reduced the need for emergency colectomy. However, impact of biologics on longer-term colectomy risk is unclear. Methods A retrospective cohort study of adult patients aged ≥18 years hospitalized with acute exacerbation of UC requiring hospitalization and managed with intravenous corticosteroids between 2010 and 2022 at two regional hospitals in London, Ontario, Canada. Steroid non-response was defined as requirement of medical rescue therapy or colectomy. Results A total of 264 adults hospitalized with ASUC were included in the analysis (male: 51.1% [n=136], mean age at admission: 40.8±17.8 years). The majority had extensive colitis (71.3% [n=169]) at the time of diagnosis. 46.3% (n=118/255) presented within one year of disease onset and 23% (n=61) had ASUC as their first presentation with UC. 25.7% (n=66/257) of patients had prior purine analogues and 23.3% (60/257) had previous biologics prior to ASUC presentation. After admission, 55.7% (n=147) responded to intravenous corticosteroids. Of the steroid non-responders, 37.5% (n=99) patients were managed with infliximab rescue therapy and only one patient received tofacitinib rescue therapy. Median CRP, stool frequency and Lindgren index score were statistically significant between steroid responders and non-responders (Table 1). A higher proportion of steroid non-responders had prior exposure to biologics or tofacitinib compared to steroid responders (31.9% vs 16.3%, p<0.01). On multivariate analysis for various factors predicting steroid non-response, assessment by Oxford criteria on day 3 was the only factor that was statistically significant (odds ratio 4.70 (95% CI 1.06-20.8), p = 0.04). Oxford criteria on day 3 had a sensitivity, specificity of 58.6% and70.8%, respectively for predicting steroid non-response. 8% (n=21) required colectomy during index admission. An additional 13% (n = 32) underwent colectomy within 12 months of discharge, for which there was no difference between steroid responders and non-responders (12.2% vs 14.7%). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 8% (20/245) and 5.4% (12/223) respectively. Hospitalization with UC exacerbation rate following discharge was 17% (38/223). Conclusion 8% of patients admitted for ASUC require colectomy during the same admission and additional 13% required colectomy within 12 months of discharge. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates remain high.

P1024 The current role of Tofacitinib in acute severe ulcerative colitis in adult patients: A systematic review and pooled analysis

Abstract Background Despite rescue therapy, acute severe ulcerative colitis (ASUC) is associated with high colectomy rates, while treatment options remain limited. Tofacitinib, a rapidly acting Janus Kinase (JAK) inhibitor, could be an effective treatment option for managing acute severe ulcerative colitis, contributing in parallel to avoiding colectomy. Methods A systematic in-depth literature search in the PubMed and Scopus databases until 20 October 2023 was undertaken for all available studies of adult patients with ASUC treated with tofacitinib. Finally, we included 18 articles from a total of 705 articles resulting from our initial search. The primary outcomes were the pooled colectomy rate and the 90-day and 6-month colectomy-free rate. Results Overall, one retrospective study, three observational studies, nine case series and five case reports incorporating 264 patients who received tofacitinib in ASUC (preferably defined according to the Truelove ad Witts criteria) identified with a follow-up period ranging from 30 days to 14 months. In total, the pooled colectomy rate was 20.4% (95% CI 15.7-25.1). The pooled 90-day and 6-month colectomy-free rates were 85.6% (95% CI 81.1-90.1) and 82.1% (95% CI 77.6-86.6), respectively (Figure). The most common side effect was infections, with C. difficile infection being the most frequent adverse event among them. Conclusion Tofacitinib may be an alternative promising option for the treatment of ASUC. Furthermore, it should be mentioned that tofacitinib could be considered a safe treatment option, taking into account that adverse effects occurred in a small amount of the patients studied. Nevertheless, randomized clinical trials are required to estimate the efficacy and safety of tofacitinib in cases of ASUC.

DOP25 Antibodies against Neutrophil Extracellular Traps (ANETAs) are associated with more severe disease course in Ulcerative Colitis

Abstract Background Antibodies against Neutrophil Extracellular Traps (ANETAs) have emerged as markers in multiple autoimmune disorders (i.e. rheumatoid arthritis and systemic lupus) associated with disease activity. We investigated the presence of ANETAs and their influence on disease course in Inflammatory Bowel Disease (IBD). Methods Serum samples from UC (n=33), Crohn's Disease (CD; n=28), and healthy controls (HC; n=8) underwent incubation with non-lytic Neutrophil Extracellular Traps (NETs) for immunofluorescence microscopy. For clinical relevance, these patients were followed over ten years to track treatment resistance, extraintestinal manifestations, surgeries, and disease recurrence (Table 1). For functional relevance, in vitro generated NETs were exposed to ANETAs, followed by quantifying macrophage-mediated clearance of these ANETA pre-treated NETs by real-time microscopy via pHrodo for 24 hours, as well as assessing pro-inflammatory cytokine (IL-6, TNF-α, IL-8, and IL-23) genetic expression levels in these macrophages. Results Among UC patients, ANETA positivity correlated with high rates of treatment resistance, extraintestinal manifestations, colorectal surgeries, and recurrence of disease like pouchitis (93.3% vs. 6.7%, 61.5% vs. 38.5%; 71.4% vs. 28.6%; 87.5% vs. 12.5%, for ANETA+ and ANETA- UC patients, respectively). CD patients with ANETAs exhibited high rates of resistance to treatment (75% vs 25%) and lower rates of extraintestinal manifestations, colectomy, and disease recurrence (38.1% vs 61.9%, 40% vs 60%, 33.3% vs 66.7%) (Fig 1A). Macrophages displayed robust engulfment of untreated NETs and those treated with healthy control sera, while ANETA-coated NETs exhibited reduced susceptibility to macrophage phagocytosis (Fig 1B). Gene expression analysis revealed a significant upregulation of pro-inflammatory cytokines (IL-6, TNF-α, IL-8, and IL-23) when NETs were incubated with serum from ANETA-positive individuals compared to sera from healthy controls (p<0.05). Conclusion ANETAs may serve as markers for a distinct subgroup of UC patients characterized by aggressive disease and poorer prognosis. The potential mechanism might involve impaired NETs clearance by, and inducing a proinflammatory response in macrophages. Discrepancies observed between UC and CD suggest diverse pathophysiological mechanisms in both diseases. Further research is imperative to comprehensively understand the underlying pathophysiology, function, and potential clinical applications of ANETAs in IBD.

P021 Higher TNFα and IL-6 mucosal levels in ulcerative colitis patients with more severe endoscopic activity

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterised by colonic mucosa inflammation. Its clinical course is marked by alternating periods of relapse and remission that impair patients' quality of life. In the last decades, novel therapies have shown to be effective for UC resulting in lower rates of colectomy. However, there is still a significant proportion of non-responding patients that change from one treatment to another, being exposed to its potential adverse events. Thus, predictive factors of response to available drugs are needed to tailor the best treatment strategy for each patient. The aim of our study was to measure TNFα and IL-6 levels in colonic biopsies from patients with UC with moderate to severe endoscopic activity. Methods A prospective, observational single-centre study was designed and it is currently on going. Adult UC patients with moderate to severe endoscopic activity (Mayo Endoscopic Score (MES) > 1) in a routine colonoscopy were included. Biopsies from inflamed (MES>1) and non-inflamed (MES=0) colon of each patient were homogenised and processed by using RIPA buffer and ultrasounds to obtain cell lysates. Human Luminex Discovery Assay (2 plex) was used for the simultaneous detection and quantitation of IL-6 and TNFα. Data are shown as percentage, median, interquartile range (IQR) and mean ± standard deviation (SD) as appropriate. Results So far, 21 patients were consecutively included (mean age 53.8 years (SD 17.0), 52.4% female). About 43% of patients had left-sided UC, 28.5% extensive UC and 28.5% proctitis. Regarding endoscopic activity, 61.9% of patients showed MES=2 and 38.1% were MES=3. Fourteen patients (66.6%) were bio-naïve and 7 (33.3%) had been exposed to anti-TNFα. IL-6 was detected in biopsies from colon with MES ≥ 2 of 18 (85.7%) patients, of which 10 (55.6%) patients also TNFα was found. Neither IL-6 nor TNFα were detected in biopsies from non-inflamed colon (p=0.00). Median IL-6 in inflamed colonic samples from patients with MES-2 was 25.6pg/ml (IQR 0.2-74.3) and 92.2pg/ml (IQR 16.9-314.3) in those with MES-3 (p=0.09). Median TNFα in inflamed colonic biopsies from patients with MES-2 was 0.0pg/ml (IQR 0.0-20.0) and 22.2pg/ml (IQR 0.0-34.3) in patients with MES-3 (p=0.12) (Figure 1). No differences were found in TNFα levels between anti-TNFα naïve patients and those patients previously exposed to anti-TNFα (p=0.96). Conclusion IL-6 and TNFα are elevated in inflamed colonic mucosa, particularly in those patients with more severe endoscopic activity, while they are not found in non-inflamed colonic mucosa. The correlation between cytokine levels and endoscopic severity suggests their potential as biomarkers for treatment response.

P855 Have biological agents changed the need for abdominal surgery in inflammatory bowel disease over time?

Abstract Background Inflammatory bowel disease (IBD) is a chronic relapsing-remitting inflammatory intestinal disorder with two main categories: Crohn’s disease (CD) and ulcerative colitis (UC). CD patients can develop strictures and penetrating complications over time, that can lead to an increased number of bowel resections which, if extensive, can end up as short bowel syndromes. Aggresive UC is related to an increased colectomy rate. Controlling flares in CD and achieving mucosal healing in UC may decrease the need for abdominal surgery. Irruption of biological agents at the begining of the twenty-first century could be related to the fulfillment of both objectives decreasing number of surgeries. Our aim was to analyze the impact of biological treatment in abdominal surgery among patients with CD and UC. Methods We conducted a retrospective two cohort study of patients with IBD and abdominal surgery, using our prospectively collected ENEIDA data base. Patients were included in two periods of time, before and after biological irruption. The first cohort included all the patients operated between 1993 and 1998 (before biologics) and the second one between 2013 and 2018. We analyzed differences in the number of surgeries per patient and time between IBD diagnosis and first surgery, among other variables. Results We included 55 patients (89.1% CD and 10.9% UC) in the first cohort and 69 patients (82.6% CD and 17.4% UC) in the second one. 44 patients in the second cohort (63.8%) received biological agents before first surgery. There were no significant differences in the number of surgeries (two or more) per patient in both periods of time (10.9% vs 7.3%, p 0.69). The main indication of surgery was strictures (44.6% vs 46.6%) followed by penetrating complications (25.0% vs 30.1%) and medical refractoriness (21.4% vs 15.1%). No differences were observed in the reason to indicate surgery (p 0.78). The main surgical procedure was ileocecal resection (60.0% vs 54.1%), followed by small bowel resection (11.7% vs 17.6%) and proctocolectomy (10.0% vs 5.4%), without significant differences over time (p 0.67). There were 7 immediate post-surgical complications in both cohorts (11.3% vs 9.5%) without significant differences between them (p 0.94). The median time between IBD diagnosis and first surgery was greater among patients in the second cohort who had received any biological agent (19.0 vs 71.2 months, p<0.05), [image 1]. Conclusion Biological treatment considerably increases the time between IBD diagnosis and the first surgery. Future research will allow us to determine if this is associated to less surgeries in each patient and a reduction in long-term post-surgery complications (short-bowel syndrome, abdominal adhesions, eventrations, etc).