Need For Colectomy Research Articles

P0481 Real-World Analysis of Disease Progression in Ulcerative Colitis: A Comparative Study Across Diagnostic Eras at a Tertiary IBD Center

Abstract Background Ulcerative colitis (UC) is a chronic condition characterized by a relapsing-remitting course, leading to cumulative systemic damage and disease progression. This progression may include extension of colitis, new extraintestinal manifestations (EIMs), dysplasia/colorectal cancer (CRC), and the need for colectomy. This study aimed to compare disease progression based on the time of diagnosis, to assess the impact of new therapeutic options. Methods Retrospective study at Reina Sofía University Hospital, analyzing all UC patients diagnosed within the past 10 years (2014-2023, cohort B) and a matched cohort diagnosed prior to 2014 (cohort A). Disease progression was defined as the first occurrence of new EIMs, new dysplasia/CRC, need for colectomy, or progression of UC extension. Kaplan-Meier analysis was used to calculate time to progression events. Results Of 643 patients identified, 72 were excluded, leaving 571 for analysis. Among them, 194 (34%) were diagnosed before 2014 and 377(66%) within the last decade (2014-2023). Median age at diagnosis was 39.5 years (IQR 27.3–54.2), and 304 (53.2%) were male. Initial disease extent was: proctitis 147(25.7%), left-sided colitis 203 (35.6%) and pancolitis 191 (33.5%). At diagnosis, 40 (7%) had EIMs. During a median follow-up of 7.1 years (3.7–13.3), 223(39.1%) patients experienced disease progression, including extension of colitis in 57(10%) cases, new EIMs in 114 (20%), colectomy in 46 (8.1%), and dysplasia/CRC in 56(9.8%). Patients diagnosed within the last decade showed a shorter time to progression compared to those diagnosed prior to 2014 (log-rank test, p<0.0001). This trend was also observed for new EIMs (p=0.01), dysplasia/CRC (p<0.0001), and disease extension (p=0.014) (Figure 1B-E). However, no significant difference was found in time to colectomy between groups (p=0.31) (Figure 1F). First maintenance therapy was mesalazine in 366(97.9%) of patients diagnosed within the last decade compared to those diagnosed previously 178(96.7%). Corticosteroids were used at some point in 379(69.4%), median number of corticosteroid courses of 2(1-4). Advanced therapy during follow-up was prescribed in 94(24.9%) of patients diagnosed in the last decade compared to 66(34%) of those diagnosed previously, p=0.022. However, time to advanced therapy prescription was significantly shorter in patients with recent diagnosis (log-rank test p=0.014) (Figure 1A) Conclusion A substantial proportion of patients with UC experienced disease progression within a follow-up period of less than 10 years. Despite the availability and earlier use of advanced therapeutic options, disease progression was observed to occur sooner in patients diagnosed within the last decade, compared to those diagnosed before 2014.

P1029 Janus Kinase Inhibitors for the Management of Acute Severe Ulcerative Colitis: A Multicentre Study

Abstract Background Acute Severe Ulcerative Colitis (ASUC) is a medical emergency, with limited therapeutic options available for medical management. Tofacitinib and Upadacitinib are novel Janus Kinase inhibitors (JAKi), with proven efficacy for ulcerative colitis (UC). This study aimed to examine the outcomes of patients treated with JAKi for ASUC in a real-world population. Methods A retrospective multi-centre study was conducted including patients (≥18 years) with ASUC commenced on Tofacitinib or Upadacitinib from April 2021 to April 2024. ASUC was defined according to Truelove and Witt’s criteria. Demographic and clinical data were recorded at admission, JAK induction, discharge, week 8, week 16 and 1 year post-induction. The primary outcome was need for colectomy. We further evaluated adverse events and drug-specific response. Results A total of 124 patients were included from 11 Australian Inflammatory Bowel Disease (IBD) centers. Tofacitinib was used in 49%, while Upadacitnib was used in the remainder. 58% of patients received JAKi as first line salvage therapy, while the remainder received JAKi sequentially after failure of first line infliximab therapy. The rate of colectomy during admission was 17% and 40% by 1 year. There was no significant difference between rate of colectomy during index admission (p=0.38), or 1 year post induction (p=0.24) between Tofacitinib and Upadacitinib. There was a significantly increased risk of inpatient colectomy for those receiving sequential salvage compared to initial JAKi salvage (p=<0.01). However, there was no significant difference in the rate of colectomy in either cohort up to 1 year post induction (p=0.19). Clinical response was observed in 45% of patients by day 3 of induction and 65% by day 7. Clinical remission rates were 40% by week 8 and 65% by week 16. Biochemical remission was achieved in 51% by week 16. Mucosal healing was achieved in 47% of patients who underwent repeat endoscopy within 16 weeks of induction. Adverse events occurred in 16% of patients, all of which were minor and did not require hospitalisation. The most common events noted were acne (7%) and nasopharyngitis (6%). Conclusion Jaki demonstrate effectiveness and safety for the management of ASUC. There was no significant difference in the inpatient colectomy rate between Tofacitinib and Upadacitinib. There was a significantly higher rate of inpatient colectomy for patients requiring sequential salvage therapy, but no significance when patients were followed up to 1 year. There is variability in prescribing practice between dosage of Tofacitinib and Upadacitinib, duration and dosage of corticosteroid wean, and the use of prophylactic PJP and VTE prophylaxis.

P0411 Utility of Intestinal Ultrasound as a predictor of Severe Ulcerative Colitis response to treatment

Abstract Background Severe Acute Ulcerative Colitis (ASUC) is a serious complication of UC that requires an early response to treatment assessment and which clinical and analytical evaluations are often inadequate. In this setting, intestinal ultrasound (IUS) could be helpful, given its accuracy in evaluating inflammatory activity and non-invasiveness. The aim of this study was to determine whether basal IUS findings and index could predict ASUC patients’ response to corticosteroid treatment. Methods A retrospective descriptive study was done including ASUC patients admitted to our hospital between January 2019 and January 2024 whose IUS had been performed before corticosteroid treatment. Variables related to clinical and analytical activity at admission and after treatment, corticosteroids response and second-line therapy requirement were also collected. In addition, the need for colectomy during the episode and at 52 weeks of follow-up was analysed. Results 43 patients were included. Their and IBD baseline characteristics are summarized in Table 1. The 58% (25) of patients responded to corticosteroids. Regarding clinical response, the responders presented lower mean SAI index of 6.6, than non-responders (7.82), finding statistically significant differences (p=0.02). Truelove-Witts severity index was also lower among responders (16.75) than between corticosteroid-refractory patients (18.1), although no statistical significance was observed (p=0.11). Responders showed lower levels of CRP (18.5 mg/L) and FC (2007.5 µg/g) than refractory patients (CRP= 26.2 mg/L, FC=3185.1 µg/g) although the differences found were not significant (CRP, p=0.24; FC, p=0.23). Regarding baseline IUS, the responders had less parietal thickness (5.9 mm) compared to non-responders (5.8 mm), p=0.78. In addition, non-responders obtained major Simple US Score (11.1) than the other group (8.93), finding statistically significance (p=0.04). However, no significant differences (p=0.089) were observed in UCIUS score (responders 8.88, non-responders 8.97) or baseline MUC (p=0.78) between both groups (10.35 responders, 10.2 non-responders). Conclusion ASUC-IUS activity is related with corticosteroid clinical and analytical response, which demonstrates the role of IUS in early response to treatment assessment. Having found statistically significance or very close to significance differences with a limited sample size, statistical power and therefore, a greater risk of committing type 2 error make results even more paramount. Therefore, our study shows that IUS is a useful predictor of ASUC response to treatment. We hope that with this evidence the use of IUS monitoring becomes a closer reality to ASUC patients.

P0617 Feasibility and safety of endoscopic submucosal dissection in inflammatory bowel disease (ESDEUR-IBD): an interim analysis of European retrospective study

Abstract Background Colectomy is the primary treatment for dysplastic lesions in inflammatory bowel disease (IBD). Since the development of advanced endoscopic techniques, the management of dysplasia is evolving. Endoscopic submucosal resection (ESD) could be used in selected cases at referral centres as an alternative to colectomy. However, the feasibility and safety in IBD remains limited. Main aim: To evaluate en-bloc resection rate and the need of colectomy due to ESD failure in IBD. Secondary aims: to assess the complications of ESD, the local recurrence of dysplastic lesions, the presence of synchronous and metachronous lesions and the risk of IBD relapse following the procedure. Methods Multicentre, retrospective study of IBD patients who underwent ESD for suspected colonic dysplastic lesions at least one month before the inclusion date. Patients with total colectomy before ESD, invisible dysplasia at the time of ESD, or pregnancy were excluded. En-bloc resection rate and colectomy due to ESD failure at the short term were evaluated by logistic regression analysis. The risk of IBD relapse was evaluated by Cox regression analysis. Results Forty-eight patients from 16 centres were included: 36 with ulcerative colitis, 9 with Crohn’s disease and 2 with IBD-unclassified. The mean age at ESD was 63 years (SD 13). The majority of the lesions (n=28, 60%) were located in rectum. Forty lesions (87%) were located in areas previously inflamed. En-bloc and R0 were achieved in 45 (94%) and 37 patients (77%), respectively. Colectomy due to ESD failure was required in 4 patients (8.3%) (Figure 1A). No risk factors were associated with colectomy in multivariable analysis, including inflammatory activity, IBD treatments or characteristics of the lesions. Complications occurred in 16 patients (33%): 6 required pharmacologic therapy, 5 needed endoscopic or radiologic intervention, and 2 underwent surgery (Table 1). No deaths were reported. At least one surveillance colonoscopy after ESD was performed in 35 patients (73%). Local recurrence was observed in 2 patients while other dysplastic lesions were detected in 9 (29%) during the follow-up (median 2.5 years, IQR 0.5-4). All of these lesions were removed endoscopically. Synchronous and metachronous lesions were identified in 4 (25%) and 7 patients (26%), respectively. IBD relapse occurred in 8 patients during the follow-up, with an incidence rate of 7% person-year (CI 95%:3-15) (Figure 1B). Conclusion ESD avoids colectomy in 80% of IBD patients with dysplastic lesions. One-third of the patients experienced complications, all of them resolved with no sequelae. Given the risk of new dysplastic lesions, ongoing monitoring with surveillance colonoscopies is recommended.

P0461 Does Number of Truelove and Witts’ Systemic Criteria at Time of Presentation with Acute Severe Ulcerative Colitis have an Effect on Severity of Systemic Features and Patient Outcomes?

Abstract Background Acute Severe Ulcerative Colitis (ASUC) is a medical emergency that occurs in 15-25% of UC patients during their disease course. The Truelove and Witts’ criteria (TWC) is used to identify patients with ASUC at time of presentation. One study showed that patients with more systemic TWC on admission were more likely to undergo colectomy, but no other outcomes were reported.1 We hypothesised that an increasing number of TWC systemic features at time of presentation would correlate with systemic toxicity, which may impact on patient outcomes. Specifically, we evaluated whether patients with ASUC who had a higher number of TWC systemic features was associated with timely investigations, use of empiric antibiotics, rescue therapy and need for colectomy. Methods A retrospective review was conducted on all ASUC presentations to a quaternary Sydney hospital over a 10-year period (January 2014 to May 2024). A modified TWC was used to identify ASUC as ≥6 bloody bowel motions daily and presence of at least one systemic feature, including heart rate (HR) >90 bpm, temperature >37.8°C, haemoglobin (Hb) <105 g/L, and C-reactive protein (CRP) ≥30 mg/L.2 Patients were classified based on number of systemic TWC met at time of presentation. Data on antibiotic prescription, time taken for abdominal imaging (XR or CT), time to flexible sigmoidoscopy, time to and use of rescue therapy, time taken for surgical review and colectomy, and length of stay were compared between groups. Results During the study period, there were a total of 617 presentations to hospital with ulcerative colitis and 172 ASUC presentations, as defined by TWC. Most presentations had ≤2 systemic features present (73.8%, n= 127). Figure 1 demonstrates that systemic toxicity was increased in patients who had more than one TWC systemic feature at time of presentation. These patients had higher average HR (p <0.05), higher temperature (p <0.05), higher CRP (p <0.05), and lower Hb (p <0.05). Table 1 shows comparative results of investigation and treatment outcomes in those presenting with one, two, three or four systemic features. Conclusion ASUC patients with more TWC systemic features on presentation had significantly increased features of systemic toxicity, with higher average HR, temperature, CRP and lower Hb. Patients presenting with a higher number of TWC systemic features may allow clinicians to more easily recognise ASUC and therefore, were more likely to receive empirical antibiotics and timely flexible sigmoidoscopy. However, treatment outcomes, as defined by need for, and time to rescue therapy, colorectal surgery review, colectomy and length of stay, appeared similar regardless of number of TWC systemic features present and evidence of systemic toxicity on presentation.

P0647 Impact of Age and Comorbidities on Treatment Outcomes and Mortality in Patients Admitted for Ulcerative Colitis Flares: A 20-Year Retrospective Cohort Study

Abstract Background Approximately one-fourth of patients with inflammatory bowel disease (IBD) are aged 60 or older, increasing the challenge of managing disease-related comorbidities compounded by age-related conditions. This study aims to explore the influence of age and comorbidities on response to first-line and rescue therapies, need for surgery, and mortality in the context of UC admissions. Methods This is a retrospective cohort study including all patients hospitalized for ASUC from 2003 to 2023 at the Reina Sofía University Hospital. Participants were grouped by age (<60 years, ≥60 years). We analyzed baseline characteristics, severity at admission, steroid response, complications, treatment intensification, need for colectomy, and mortality. Results A total of 419 patients were hospitalized for UC flares, with 19.6% (n=82) being elderly (≥60 years). Comorbidity (Charlson index ≥2: 42.7% vs. 7.3%, p<0.0001) and polypharmacy (61% vs. 10.4%, p<0.0001) were more frequent among older adults, Table 1. Regarding UC, no significant age-related differences were observed in disease extent or severity at admission (clinical, biochemical, or endoscopic parameters). Complications during hospitalization and corticosteroid response on days 3 and 5 were also similar across age groups. However, older patients showed lower rates of treatment intensification (41.7% vs. 55.7%, p=0.021), reduced access to biologicals anti-TNF agents or cyclosporine (13.1% vs. 26.3%, p=0.011), higher ICU admission rates (2.4% vs. 0.3%, p=0.044), greater readmission rates (28.9% vs. 16.9%, p=0.013), higher colectomy rates (32.1% vs. 17.4%, p=0.003), and increased one-year mortality following hospitalization (11.9% vs. 0, p<0.0001). In multivariate analysis, advanced age remained a significant predictor for limited access to rescue therapies, Table 2. Conclusion In our study, older patients hospitalized for UC exhibited similar clinical characteristics regarding flare severity and corticosteroid response compared to younger patients. However, this subgroup had higher colectomy rates, ICU admissions, readmissions, and one-year mortality, along with reduced access to rescue therapies, including anti-TNF agents and cyclosporine.

P0738 Apulian Network for Inflammatory Bowel Disease (AN-IBD) safety profile: Pilot data

Abstract Background The Apulian Network for Inflammatory Bowel Disease (AN-IBD) is a prospective observational regional database recently approved by the Ethics Committee in Apulia (Italy), enrolling all IBD patients with an established diagnosis and focusing on the safety and effectiveness of all licensed therapies. We aimed to evaluate the safety profile of IBD therapies registered in patients enrolled in the participating centres and to record the occurring adverse events. Methods The AN-IBD involves 19 centres across Apulia, selected based on their capacity to prescribe advanced IBD therapies. In the six months following the ethical approval, we recorded unselected patients in the database and stratified them by disease type, age, sex and type of treatment. The occurrence of infusion reactions (local and systemic), infections, IBD-related hospitalization, need for colectomy, malignancies, thromboembolic events, and laboratory alterations were recorded. Their severity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results A total of 420 patients were enrolled, consisting of 251 males (59,76%) and 169 females (40,24%), with a median age of 44 years. Among them, 243 (57,86%) were diagnosed with ulcerative colitis, 156 (37,14%) with Crohn’s disease and 21 (5%) with unclassified colitis. Overall, 341 patients (81,19%) were treated with advanced therapy, including biologic therapy and small molecules. A total of 33 (7,85%) adverse events were recorded comprehensively, and most of them were graded as moderate according to the CTCAE. Twenty-three patients were treated with biologic therapy (70%), seven with small molecules (21%), one with immunomodulators (3%) and two with conventional therapy (6%). The most common adverse events were infusion reactions, with fourteen cases recorded (42%), followed by eight cases of infective complications (24%), predominantly due to cytomegalovirus reactivation. Other recorded adverse events included IBD-related surgery (15%), malignancies (9%) and altered liver enzymes (9%). Conclusion These preliminary findings evaluate the real-world prevalence and nature of adverse events among the population enrolled in our newly developed multicentre regional cohort. The establishment of this new database, given the absence of a national registry, will allow for closer monitoring of IBD patients undergoing conventional and advanced therapies and will increase awareness of the safety of these treatments.

P1176 Low serum albumin levels are associated with higher colectomy rates in patients with moderate-to-severe ulcerative colitis on tofacitinib

Abstract Background This study aimed to evaluate the real-world, long-term effectiveness and safety of tofacitinib in a large cohort of patients with refractory or difficult-to-treat ulcerative colitis (UC). Methods A multicentre, retrospective, observational cohort study was conducted, including patients with moderately to severely active UC who received tofacitinib for at least 8 weeks. Outcomes assessed included clinical remission and response, endoscopic response and remission, biochemical response and remission, steroid-free clinical remission, primary and secondary loss of response, drug discontinuation, dose optimisation, the need for colectomy, and adverse events over a follow-up period of up to 30 months. Results The study included 127 patients with UC, with a mean age of 40.3 ± 14.2 years; 58.2% were male, 75.6% had pancolitis, and 79.5% had previously failed at least one biological therapy, predominantly anti-TNF agents (70.1%). Clinical remission was achieved by 31.5% of patients at weeks 12–16, 46.5% at 26 ± 4 weeks, and 37.0% at 1 year. Steroid-free clinical remission was observed in 28.6%, 44.8%, and 37.1% of patients at these respective time points. Biochemical remission occurred in 33.6% of patients at 26 ± 4 weeks and 29.3% at 1 year. Endoscopic response and remission within 1 year were reported in 46.0% and 15.3% of patients, respectively. Ten patients (7.9%) required colectomy, and 13 patients (10.2%) were hospitalised, all of whom had previous exposure to biologics. The colectomy rate was significantly higher in patients with baseline serum albumin levels ≤ 3.5 g/dL (21.4% vs. 4.1%, p = 0.013) (Table 1). Conclusion This large, long-term real-world study demonstrated that tofacitinib effectively induced clinical remission and endoscopic improvement while preventing colectomy for over 30 months in patients with predominantly biologically refractory UC. The safety profile was favourable. However, baseline hypoalbuminemia was associated with higher colectomy rates, highlighting its prognostic significance.

P0599 Efficacy and safety of intravenous methylprednisolone and hydrocortisone in Acute Severe Ulcerative Colitis (ASUC) – a posthoc analysis of the IASO trial

Abstract Background Intravenous corticosteroids remain the cornerstone of initial management of ASUC. Methylprednisolone and hydrocortisone are two commonly used intravenous (IV) steroids recommended in guidelines.1 Methylprednisolone has less frequent dosing requirements and is reported to have weaker mineralocorticoid effects compared to hydrocortisone, theoretically reducing the risk of hypokalaemia.2 Comparative data on the efficacy and safety of the two drugs in ASUC are lacking. In the IASO trial patients with ASUC were randomised to receive IV corticosteroids according to local practice, alongside either placebo or anakinra. There were no differences in the efficacy and safety outcomes for groups treated with placebo or anakinra. In this posthoc analysis we examine efficacy and safety outcomes for patients treated with IV methylprednisolone and hydrocortisone. Methods Data from anakinra and placebo treated groups were pooled and efficacy compared according to choice of IV corticosteroid, using logistic regression to control for potential confounders (sex, new diagnosis UC, previous ASUC, baseline albumin and baseline CRP). Adverse events were assigning into one of four subgroups and then Fisher’s exact test was used to assess the significance of any difference in hypokalaemia incidence. Due to posthoc nature of this analysis, p values are considered nominal. Results Unadjusted need for rescue therapy by day 10 was 17/39 (44%) for methylprednisolone and 21/67 (31%) for hydrocortisone respectively, with no significant difference between groups (p=0.205). Unadjusted need for colectomy by day 98, was 6/38 (16%) for methylprednisolone and 3/67 (4%) for hydrocortisone respectively with no significant difference between the groups (p=0.047). Logistic regression identified baseline albumin as a significant predictor in the need for rescue therapy by day 10, but not the type of corticosteroid. None of the predictors were significant for day 98 colectomy, including type of corticosteroid. Safety profiles were broadly comparable, although rate of hypokalaemia was 0/19 (0%) in the methylprednisolone group and 6/58 (10%) in the hydrocortisone group (p=0.33). Conclusion This posthoc analysis showed similar rates of rescue therapy in patients treated with IV methylprednisolone and IV hydrocortisone in the initial management of ASUC. Safety profiles were similar, although the incidence of hypokalaemia appeared higher in the hydrocortisone group. These results suggest that IV methylprednisolone is an appropriate choice for treatment of ASUC with efficacy and safety at least comparable to hydrocortisone and favourable dosing frequency.

P0527 Bowel Ultrasound Scan (BUS) in Pediatric Acute Severe Colitis (ASC): a multicenter prospective study on behalf of the IBD Porto group

Abstract Background Acute severe colitis (ASC) is a potentially life-threatening event. Optimal timing for second-line treatment in children is mainly based on the clinical score Pediatric Ulcerative Colitis Activity Index (PUCAI) score. The aim of our study was to evaluate the potential role of bowel ultrasound scan (BUS) in predicting short-term treatment outcomes in pediatric ASC. Methods This was a prospective longitudinal study, conducted across ten European centers between March 2020 and March 2024. Biologic-naïve children with Ulcerative Colitis hospitalized for ASC, either at diagnosis or at disease relapse, were included. Each patient underwent two BUS, the first one within the first 48 hours of from IVCS intravenous corticosteroids administration and the second one within 5-7 days from treatment initiation. Key metrics assessed included colonic wall thickness (CWT), colonic wall stratification (CWS) and colonic wall blood flow via power Doppler. All the above-mentioned ultrasound parameters were recorded in 4 different segments of the bowel: ascending, transverse, descending, and sigmoid colon. Furthermore, Milan ultrasound criteria (MUC) score was also calculated for each colonic quadrant. Clinical, laboratory, and treatment data were gathered during hospitalization and at 2-, 4-, and 8-weeks follow-up. Results 59 patients (61% males, median age at ASC: 14.2 years) were included. Almost 60% of patients had pancolitis, 22 (37.3%) experienced ASC at disease onset. Table 1. summarizes patients’ characteristics at ASC. 38 (64.4%) patients failed to respond intravenous corticosteroids (IVCS) and required second-line therapy with infliximab (IFX). Patients who required step-up treatment with IFX had higher colonic wall thickness (CWT) and more frequently an increased vascularization (Limberg score > 2) (p=0.041 and p=0.005, respectively). Furthermore, patients who failed to respond to IVCS and required escalation to IFX had a higher MUC score at firs BUS (p=0.042). Ten patients (16.9%) failed to respond to medical treatment and required short-term colectomy (within 8 weeks of follow-up). Patients who required colectomy had a higher CWT both at first and at second BUS (p=0.033 and p=0.004, respectively). Moreover, patients who responded to medical therapy had higher DeltaCWT (difference between worse CWT at first and at second BUS) compared to those who required surgery (p=0.0018). Conclusion BUS may serve as an effective noninvasive tool to predict first-line therapy failure and the need for colectomy in patients with ASC. Its implementation in clinical practice may enable physician to support clinical evaluation and tailor treatment escalation upon patient’s individual characteristics.

P0545 Risk of rapidly progressive disease course in patients with pediatric-onset ulcerative colitis

Abstract Background Ulcerative colitis (UC) disease course is unpredictable at diagnosis and its management is still based on a “onesize-fits-all” approach. We aimed to investigate predictive factors of a rapidly progressive course in pediatric UC. Methods Retrospective case-control study conducted at Pediatric Gastroenterology Unit of Umberto I Hospital in Rome. We included newly diagnosed UC patients aged < 18 years, with a minimum follow-up of 24 months. Demographic and clinical data, laboratory, endoscopic and histologic findings at diagnosis were collected and compared between patients with indolent UC and those with a rapidly progressive (RP) course, defined if they experienced one of the following within the first 24 months after diagnosis: acute severe colitis under antiTNFα unresponsive to IV steroids, need for colectomy and need for second-line biologics or advanced small molecules with at least two different mechanisms of action1. Results One hundred and forty-two children were included, 61 (43 %) with a RP course and 81 (57 %) with an indolent course of disease. RP children had higher age (11.3 ± 4.2 vs 9 ± 4, p=0.0002) and a higher PUCAI (50 ± 13 vs 40.4 ± 12, p<0.0001) at diagnosis then those with indolent course. Hemoglobin was lower in RP group (11.6 ± 1.8 vs 12.4 ± 1.2 g/dL, p=0.001). RP children had higher rate of cecal patch at endoscopy (19% vs 2% p=0.001) and lower rate of sclerosing cholangitis (0 vs 8%, p=0.01). Endoscopic activity was more severe in RP compared to indolent patients as shown by the higher rate of Mayo 3 score (18% vs 2%, p=0.002) and median UCEIS (3.9 ± 1 vs 3.3 ± 0.9, p=0.001). The rate of severe histologic activity as graded by the local pathologist was higher in RP children (18% vs 1 %, p=0.004). The presence of a cecal patch at endoscopy was the only independent predictor for a rapidly progressive disease at the multivariate logistic regression analysis [OR 9.2 (95% CI 1.9-67.1), p=0.0009]. Conclusion Children with a RP course seem to present with older age and a more clinically and endoscopically severe disease. However, only the endoscopic finding of a cecal patch emerged as an independent predictor of this course. These findings warrant confirmation in larger prospective cohorts to support a future personalized approach to UC.

Anti-TNF nonresponse in ulcerative colitis: correcting for mucosal drug exposure reveals distinct cytokine profiles.

It remains unclear why up to 30% of ulcerative colitis (UC) patients do not respond to tumor necrosis factor inhibitors (TNFi). Validated biomarkers for nonresponse (N)R) are lacking. Most studies investigating underlying mechanisms do not differentiate between pharmacokinetic and inflammatory mechanisms. We therefore aimed to develop a framework to correct for mucosal drug exposure (MDE) and applied this to mucosal cytokine profiles previously linked to (N)R. In a prospective international cohort, we studied patients with active moderate-severe UC starting TNFi treatment. Patients underwent endoscopy before (baseline) and after induction treatment (follow-up). NR was defined as the absence of Mayo endoscopic subscore improvement by central read or need for colectomy. The ratio of mucosal concentrations of TNFi/TNF was used to define high or low MDE. Mucosal concentrations of interleukin-6 (IL-6), Oncostatin M (OSM), interleukin-10 (IL-10), and interleukin-12/23p40 (IL-12/IL-23p40) were measured. Fifty-four UC patients were included (43 infliximab, 11 adalimumab) of whom 39 (72%) were endoscopic responders (after a median treatment of 62 days [48-96]). NR with high MDE had high IL-6 at both time points. R with low MDE exhibited low mucosal IL-10 at baseline. At follow-up, high OSM was associated with NR (irrespective of MDE) and high IL-12/IL-23p40 with R. We incorporated MDE in mucosal cytokine research to avoid bias due to the insufficient presence of anti-TNF. When applied to mucosal cytokines previously linked to (N)R, IL-6 appears to drive inflammation in TNFi-resistant UC patients, while OSM seems to parallel inflammation and does not cause refractoriness.

Acute severe ulcerative colitis: using JAK-STAT inhibitors for improved clinical outcomes

Acute Severe Ulcerative Colitis (ASUC) is a well-known and potentially fatal disease state, characterized by symptoms of systemic toxicity including fever, severe anemia, elevated inflammatory markers, and autonomic instability. The life-threatening nature of this condition requires clinicians to make prompt diagnoses and take rapid action, either directing patients towards surgical interventions or medical management. Failure to treat ASUC may lead to toxic dilation of the colon, hemorrhage, or sepsis. Current algorithms suggest the use of intravenous (IV) corticosteroids upon diagnosis, with transition to oral corticosteroids, calcineurin inhibitors or tumor necrosis factor (TNF) inhibitors upon reduction of severe symptoms for candidates deemed to be amenable to medical management. Within these classes, TNF inhibitors such as Infliximab (IFX) have proven to be the most safe, efficacious, and tolerable for patients. While IFX has much data supporting its benefits in achieving short term remission, there are still high rates of long-term need for colectomy and failure to maintain remission. This is due to interactions between the inflamed gastrointestinal tract, the increased metabolic activity seen in ASUC, and intrinsic pharmacodynamic properties of IFX. Certain novel studies suggest that Janus Kinase (JAK-STAT) inhibitors such as Tofacitinib and Upadacitinib are potent agents to salvage clinical remission achieved by IFX, upon its failure. Here we discuss methods to optimize the dosing of IFX to maximize its efficacy, while exploring recent work done on the safety and efficacy of JAK-STAT inhibitors as a salvage therapy, therefore suggesting a novel treatment algorithm to improve clinical outcomes in medically managed ASUC patients.

Superiority of Frailty Over Age in Predicting Outcomes Among Clostridium Difficile Patients: Evidence from National Data

BackgroundClostridium difficile infection (CDI) has become a significant healthcare issue with increasing morbidity and mortality in the US and Europe. Frailty, characterized by reduced physical reserves and resistance to stressors, is linked to poor outcomes but its impact on CDI patients remains underexplored. This study seeks to address this gap through a nationwide analysis. MethodsUsing the National Readmission Database from 2016 to 2020, we employed the International Classification of Diseases, 10th revision, Clinical Modifications codes to identify adult patients admitted with CDI. We further stratified CDI hospitalizations based on frailty. Utilizing a regression model, we assessed the impact of frailty on CDI outcomes. ResultsWe included 144,611 CDI patients of whom 98,167 (67.88%) were frail. Multivariate analysis showed that frail CDI patients had significantly higher mortality (adjusted odds ratio (aOR) 4.87), acute kidney injury requiring dialysis (aOR 9.50), septic shock (aOR 14.23), and intensive care unit admission (aOR 6.80). CDI-specific complications were more likely in frail patients, including toxic megacolon (aOR 10.22), intestinal perforation (aOR 2.30), need for colectomy (aOR 3.90) and CDI recurrence (aOR 3.65). Resource utilization, indicated by hospitalization charges, length of stay, and 30-day readmission rates, was greater among frail patients. ConclusionOur study underscores the significant association between frailty and various critical endpoints of CDI, including its incidence, mortality, and recurrence. Additionally, frailty independently predicts higher resource utilization and elevated 30-day readmission. Recognizing frailty as a determinant of CDI outcomes can aid clinicians in risk stratification and guide tailored interventions for this population.

Predictors for colectomy in patients with acute severe ulcerative colitis: a systematic review and meta-analysis

ObjectivesAcute severe ulcerative colitis (ASUC) poses challenges to patient management owing to its high surgical rate. This study aimed to identify predictors of colectomy in patients with ASUC.DesignThis is a...

Assessing Clinical Outcomes for C. diff Polymerase Chain Reaction (PCR)-positive, Enzyme Immunoassay (EIA)-negative Patients

Background: In August 2021, Saint Luke’s Health System (SLHS) transitioned Clostridioides difficile (C. diff.) testing from polymerase chain reaction (PCR)-only to two-step enzyme immunoassay (EIA) reflex following PCR+ for suspected C. diff. infection. Uncertainty in patient management may arise when PCR and EIA testing differ. Previous studies suggested that disease severity varies when a patient’s results demonstrate PCR+ and EIA- due to possible colonization. Clinicians may not treat if diarrhea self-resolves, patients remain stable, or alternate causes of diarrhea exist. We compared clinical outcomes of patients who received treatment to those who did not. Methods: This was a retrospective cross-sectional study from August 2021-August 2023 in a multi-site, integrated health system, comparing 181 inpatients with PCR+/EIA- C. diff. test results stratified by no treatment (0-48 hours of C. diff. targeted treatment), partial treatment (2-9 days), or full treatment (10+ days). The primary outcome was length of stay. Secondary outcomes were readmission rates, need for colectomy, intensive care unit (ICU) admission, and diarrhea resolution on day of discharge. Results: Of the 181 patients, 144 received full treatment, 17 had partial, and 20 had no treatment. Baseline characteristics were similar between groups. No significant difference was found for length of stay or any secondary outcomes (Table 1). Table 2 provides a subgroup of patients who received no treatment vs those receiving partial or full treatment. Conclusion: In this study, treatment exposure did not affect clinical outcomes for patients with PCR+/EIA- results, though sample sizes may limit generalizability. Further research is warranted regarding the clinical approach to PCR+/EIA-

Colombian experience with the use of tofacitinib in severe acute ulcerative colitis: A case series study

IntroductionTofacitinib is indicated in patients with moderate to severe ulcerative colitis (UC); however, given its rapid onset of action, it may constitute an alternative in patients with hospitalized severe acute UC. There are few data on this indication in the literature. The aim of this study was to describe the efficacy and safety of tofacitinib in the management of patients with hospitalized UC, as well as its clinical characteristics and other treatment patterns. Materials and methodsDescriptive observational study of adults and children with CUAG treated with tofacitinib between June 2019 and December 2022 in Colombia. Sociodemographic and clinical variables were collected, therapeutic response was evaluated in different periods of time and descriptive analysis of quantitative and qualitative variables was performed. ResultsSix patients (five adults and one pediatric), mean age 33.2 (SD: 8.5) years, with CUAG. Symptom remission was obtained in 100% of patients at day 7 after tofacitinib initiation. In three patients information was obtained beyond 6 months, with 100% clinical, biochemical, and endoscopic remission and without requiring colectomy. In the case of the pediatric patient, symptom remission was achieved one week after starting tofacitinib, remaining in clinical, biochemical and endoscopic remission beyond 6 months. No serious adverse events were reported in any of the cases. ConclusionsTofacitinib represents a rescue therapeutic alternative in CUAG, with rapid clinical response, adequate tolerance and less need for colectomy, being sustained for periods beyond 6 months.

Intestinal ultrasound scan predicts corticosteroid failure and colectomy risk in patients with ulcerative colitis.

Intestinal ultrasound (IUS) is an emerging modality for assessing disease activity, extent, and treatment response in ulcerative colitis. This study aimed to evaluate the potential of IUS in predicting severe flares, the need for rescue therapy (corticosteroid failure), and colectomy in patients with ulcerative colitis. We conducted a retrospective review of medical records, collecting clinical and IUS data. The Milan Ultrasound Criteria (MUC) score was used to assess ulcerative colitis severity. Group comparisons were performed to identify differences in MUC scores between mild-to-moderate and severe ulcerative colitis, between steroid responders and nonresponders, and between patients who underwent colectomy and those who did not. Receiver operating characteristic (ROC) analysis was used to predict outcomes in patients with ulcerative colitis. This analysis included 102 patients with ulcerative colitis categorized as mild/moderate (60) or severe (42). MUC scores were significantly higher in the severe ulcerative colitis group compared with the mild/moderate group ( P < 0.001). Analysis (using ROC) identified a cutoff MUC score of >8.54 to indicate severe ulcerative colitis with good sensitivity (64.29%) and excellent specificity (93.33%). Similarly, a cutoff of MUC > 10.54 showed promise in predicting corticosteroid failure, with acceptable sensitivity (50%) and high specificity (90.91%). Finally, a cutoff MUC score >12.5 demonstrated potential for predicting colectomy, exhibiting moderate sensitivity (55.56%) but excellent specificity (96.97%). IUS may be useful for differentiating severe ulcerative colitis from mild-to-moderate disease, identifying early stage failure of corticosteroid therapy, and predicting the potential need for colectomy.

Post-hospitalization Short Versus Long Steroid Taper Strategies in Patients With Acute Severe Ulcerative Colitis: A Comparison of Clinical Outcomes.

Ulcerative colitis (UC) is a chronic inflammatory colon disease characterized by relapsing flares and remission episodes. However, the optimal steroid tapering strategy in patients hospitalized for acute severe UC (ASUC) remains relatively unknown. We aim to examine the clinical outcomes in patients hospitalized for ASUC regarding variable prednisone taper regimens upon discharge. We retrospectively reviewed all adult patients admitted to our facility with ASUC between 2000 and 2022. Patients were divided into 2 groups based on the duration of steroid taper on discharge (< 6 and > 6 weeks). Patients who had colectomy at index admission were excluded from the analysis. The primary outcome was rehospitalization for ASUC within 6 months of index admission. Secondary outcomes included the need for colectomy, worsening endoscopic disease extent and/or severity during the follow-up period (6 months), and a composite outcome as a surrogate of worsening disease (defined as a combination of all products above). Two-sample t-tests and Pearson's chi-square tests were used to compare the means of continuous and categorical variables, respectively. Multivariate logistic regression analysis was performed to identify independent predictors for rehospitalization with ASUC. A total of 215 patients (short steroid taper = 91 and long steroid taper = 124) were analyzed. A higher number of patients in the long steroid taper group had a longer disease duration since diagnosis and moderate-severe endoscopic disease activity (63.8 vs. 25.6 months, p < 0.0001, 46.8% vs. 23.1%, P = ≤ .05, respectively). Both groups had similar disease extent, prior biologic therapy, and the need for inpatient rescue therapy. At the 6-month follow-up, rates of rehospitalization with a flare of UC were comparable between the 2 groups (68.3% vs. 68.5%, P = .723). On univariate and multivariate logistic regression, escalation of steroid dose within four weeks of discharge (aOR 6.09, 95% CI: 1.82-20.3, P = .003) was noted to be the only independent predictor for rehospitalization with ASUC. This is the first study comparing clinical outcomes between post-discharge steroid tapering regimens in hospitalized patients for ASUC. Both examined steroid taper regimens upon discharge showed comparable clinical results. Hence, we suggest a short steroid taper as a standard post-hospitalization strategy in patients following ASUC encounters. It is likely to enhance patient tolerability and reduce steroid-related adverse effects without adversely affecting outcomes.

SAFETY OF ANTI-TUMOR NECROSIS FACTOR AGENTS COMPARED TO USTEKINUMAB AND VEDOLIZUMAB IN ELDERLY PATIENTS WITH ULCERATIVE COLITIS

Abstract BACKGROUND Common first-line treatments for ulcerative colitis (UC) currently include anti-tumor necrosis factor (anti-TNF) agents, ustekinumab (interleukin-12/interleukin-23 receptor antagonist), and vedolizumab (integrin antagonist). However, there are safety concerns when prescribing biologic therapies to elderly patients. While these medications have all demonstrated general efficacy and safety in UC, this study aims to examine the long-term comparative safety of anti-TNF agents with vedolizumab and ustekinumab in elderly patients with UC. METHODS The Research Network on TriNetX database was accessed on September 26, 2023, to identify patients at least 65 old who were diagnosed with UC: the first cohort included patients prescribed anti-TNF agents (included adalimumab, certolizumab pegol, golimumab, and infliximab) and the second cohort included patients prescribed either vedolizumab or ustekinumab. Primary outcomes included mortality, corticosteroid use, subsequent colectomy, colon cancer, infections, and all-cause hospitalizations within 10 years after matching for age, sex, and race. All analyses were performed in real-time using built-in statistical algorithms on TriNetX. RESULTS After matching cohorts, 1,075 elderly patients with UC patients were included in each cohort as shown in table 1. Patients who were prescribed anti-TNF therapy had a significantly increased 10-year risk of mortality (10.7%) compared to patients on either vedolizumab or ustekinumab therapy (5.77%) (OR 1.96, 95% CI [1.42, 2.7], p &amp;lt;0.0001). Corticosteroid use was higher in the anti-TNF cohort (40.6% vs 34.9%, p= 0.007). There were no significant differences between the two cohorts when comparing the need for colectomy (3.26% vs 2.23%, p = 0.15) or colorectal cancer occurrence (1.67% vs 2.05%, p=0.52) within 10 years. However, the anti-TNF cohort had a higher risk of all-cause hospitalization (32.5 % vs 22%, p=&amp;lt;0.0001), respiratory tract infections (18.4% vs 14.5%, p=0.015), and urinary tract infections (10.4% vs 7%, p=0.005). CONCLUSION In elderly patients with UC, ustekinumab or vedolizumab are safer treatment options compared to anti-TNF therapy. Table 1 Demographics and Comparative 10-year Outcomes of Elderly Patients with UC.