Colectomy Rates Research Articles

P459 Hospitalization, use of biologics and surgery rates in inflammatory bowel diseases: a single-center comparative analysis between public and private healthcare systems in a tertiary unit from Latin America

Abstract Background Inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), characterized by chronic inflammation of the intestine, have a rising incidence and prevalence globally. The potential impact of socioeconomic inequality on health and mortality is well documented. In chronic diseases, the effect of inequality in assessment to healthcare can be associated with a higher frequency of complications and worse organ functionality in patients with social deprivation. In IBD, there are scarce studies comparing the differences between patients according to their socioeconomic status. Our aim was to comparatively evaluate hospitalizations, use of biologics and rates of surgery in patients with IBD between public and private healthcare systems. Methods single-center retrospective cohort study in patients with IBD from a tertiary referral unit from Latin America, between 2015 and 2021. CD and UC patients were classified into two subgroups: public and private healthcare systems. Main analyzed variables were age at diagnosis, gender, Montreal classification, new diagnoses or referred patients, smoking status, previous medications, need for IBD-related hospitalizations and abdominal surgery. Demographic characteristics, hospitalizations, need for surgery and biologics were compared between two subgroups: private and public healthcare systems. Results 500 patients were included, 322 with CD and 178 with UC. CD-related hospitalizations were frequently observed in both healthcare systems (76.28% in private and 67.46% in public). More than half of the patients had been submitted to one or more CD-related abdominal surgical procedure, with no significant difference between the subgroups. Although there was no difference in the rates of use of biological therapy in CD subgroups, infliximab was more used in the public setting (57.69% vs. 43.97%, p=0.014). There was no difference in UC-related hospitalizations between the subgroups (public 30.69% and private 37.66%, p=0.33) as well as the rates of colectomy (public: 16.83%, private: 19.48%, p=0.65). Biologics were used almost twice as often in private as compared to the public system (45.45% vs. 22.77%, p=0.001). Conclusion Patient demographics were overall similar between healthcare systems in IBD patients. There were no differences in the rates of hospitalization and abdominal surgery between the two subgroups in both diseases. In patients with UC, there was greater use of biological therapy in the private healthcare setting. Global data regarding the possible impact of social deprivation in IBD-related outcomes are warranted.

P282 Isolated colonic Crohn’s disease and extensive ulcerative colitis: is there a reel difference?

Abstract Background The management of isolated colonic Crohn's disease (CDc) is often modeled on that of Ulcerative Colitis (UCc). The aim of our study was to compare epidemiological and evolutive profiles of CDc and UCc. Methods We conducted a retrospective, descriptive and comparative study, including patients diagnosed with CDc as well as UCc, who were hospitalized in our department over a 9-year period [January 2011 - January 2020]. The group 1 included patients with CDc and group 2 included patients with UCc. Patients with less than 2 years of follow-up were excluded. Data were recorded and analyzed by SPSS software version 26. Results We included 130 patients with a sex ratio M/F= 0.68. The mean age at diagnosis was 34.85 years [6-68 years]. Sixty-three patients had CDc, while 67 patients had UCc. The two groups were comparable for age (p=0.56) and sex (p=0.54). The percentage of patients with smoking and alcoholism was also comparable between the two groups (p=0.4 and p=0.8 respectively). The presence of at least one autoimmune disease and a family history of Inflammatory Bowel Disease were more noted in patients in group 1 than in group 2 (p= 0.011 and p=0.046 respectively). The mean BMI at diagnosis was 22.28 kg/m² and was comparable between the 2 groups. The main phenotype was inflammatory (93.6%) in group 1. Twenty-five patients in group 1 (39.6%) and 22 patients (32.8%) in group 2 had associated extra-intestinal involvement (p=0.41), represented mainly by rheumatological involvement (n=39, 30%). The mean albumin level at diagnosis was 29.21 g/L and 30.96 g/L in groups 1 and 2 respectively. The occurrence of Severe Acute Colitis during follow-up was more frequent in group 2 than in group 1 (58.2% vs. 46%), although the difference was not significant (p=0.13). However, the rate of colectomy was significantly higher in group 2 (p=0.029). The use of anti-TNF therapy was significantly higher in group 1 (p=0.046). The maximum duration of hospitalization and the number of relapses were not statistically different between the 2 groups (p=0.81 and p=0.8 respectively). Finally, there was no significant difference between the 2 groups considering the use of corticosteroid or immunosuppressive therapy (p=0.88 and p=0.96 respectively). The main limit of our study is that it was conducted only in hospitalized patients who had relatively severe disease. Conclusion CDc is more prone to intensive medical treatment, whereas colectomy is more noted in UCc.

P547 Rate of Colectomy Increases within Twelve Months of Sequential Therapy for Ulcerative Colitis

Abstract Background Even the best medical treatments for ulcerative colitis (UC) are often ineffective, with up to 15% of patients requiring a colectomy within the first 10 years of diagnosis. In the current era, patients have access to an increasing number of medical therapies that may prevent and/or delay surgery. To evaluate the relative effectiveness of sequential therapies for UC, we evaluated the 12-month colectomy rate among patients switching to a second, third, or fourth-line biologic or small molecule therapy for UC. Methods We conducted a retrospective cohort study, using a new-user design, evaluating patients with commercial insurance in the MarketScan database between 2000 and 2019. The index date for the study was defined as the date of the first claim for a second, third, or fourth biologic or small molecule therapy. The primary outcome was defined as colectomy-free survival at 12 months after the index date. Significance of 12-month colectomy rates over time was evaluated using the Cochran-Armitage test of trend and a Generalized Estimating Equation (GEE) model adjusting for age (18-35, 36-55, >55), sex and index year (year 2007-2014 and 2015-2019). Results We identified 3,325 patients with UC that made at least 1 switch in biologic or small molecule therapy during the study period. Among these, 50% were female and the median age was 41 years (interquartile range 31-52 years, Table 1). The most frequent initial biologic switches were from an anti-tumor necrosis factor alpha (TNF) to an anti-TNF (1895 patients [57%]) and anti-TNF to vedolizumab (980 patients [30%]) were the most common sequences of therapies (Table 2). Overall, 392 (12%) patients underwent colectomy within 12 months of the first switch while 116 of 695 (17%) patients underwent colectomy within 12 months of the second switch. Among 161 patients that underwent 3 switches, 30 (19%) underwent colectomy within 12 months of the third switch (p<0.001, Table 3). The rate of UC-related hospitalizations in the 12 months after switch also increased significantly with each subsequent switch (11% vs. 15% vs. 19% for first, second and third switches respectively, p<0.001). The colectomy rate per switch in therapy appeared stable when stratifying by index date and age at index date (Figure 1). Conclusion Despite increases in the number of available mechanisms for the treatment of UC, a substantial proportion of patients will still require colectomy for UC. The absolute risk of colectomy within 12 months and other negative outcomes increase with each subsequent treatment. These data can help inform complex decisions regarding the timing of surgery relative to initiation of subsequent therapy in patients with medically-refractory disease.

P628 Tofacitinib in pediatric ulcerative colitis: a retrospective multi-center experience from the Paediatric IBD Porto group of ESPGHAN

Abstract Background Tofacitinib, a Janus kinase (JAK) inhibitor, has recently been approved for treatment of moderate to severe active ulcerative colitis (UC) in adults. Data on efficacy and safety in pediatrics are limited. In this multicenter study from the Paediatric IBD Porto group of ESPGHAN, we describe the short-term effectiveness and safety of tofacitinib in an international pediatric IBD cohort. Methods Retrospective review of children (2-18 years) diagnosed with UC treated with tofacitinib from 15 pediatric centers internationally. Primary outcome was corticosteroid-free clinical remission (PUCAI<10) at week 8, with secondary outcomes including clinical response (≥20 point decrease in PUCAI), colectomy rate and safety. Primary outcome was calculated utilizing non-response imputation (NRI), whereby drug cessation for any reason was considered treatment failure. Results 78 patients (43 (55%) female, mean age at diagnosis 12.5 (±2.7) years, median disease duration 20 months (IQR 10.3-38.8)), all with previous biologic failure, including 20/78 (26%) with previous failure of three biologic classes. 15/78 (19%) patients achieved corticosteroid-free clinical remission at week 8 with a further 18/78 (23%) demonstrating clinical response. 9/78 (12%) underwent colectomy by week 8, and 21/78 (27%) by week 24. Twelve adverse events were reported including five infective (three of which deemed possibly related to treatment – zoster, HSV-2 cheilitis and septic arthritis), one case of pancreatitis, and abnormal blood test results in 5 children (anemia, lymphopenia, elevated hepatic transaminases and hypercholesterolemia). Conclusion In this largest real-life cohort of tofacitinib in pediatric UC to date, tofacitinib seemed effective in at least 19% of highly refractory patients by week 8. Adverse reactions and safety were largely consistent with adult data.

P309 Accuracy of PanMayo endoscopic score in predicting long-term disease outcomes in ulcerative colitis– a promising scoring system

Abstract Background Ulcerative colitis (UC) is a systemic immune-mediated disease that affects the colon continuously. Colonoscopy plays a crucial role in management of UC that helps to assess mucosal healing objectively along the colon. Different scoring systems are available to assess severity, however most of them does not take into consideration of disease extent. Extension modified (PanMayo) Mayo endoscopic subscore (MES) system has been shown to correlate with UCEIS and Riley scores and calprotectin. Our study aimed to assess the predictive power and accuracy of PanMayo score compared to MES, UCEIS and Dublin to predict mid- and long-term disease outcomes. Methods This is retrospective, two-center study. UC patients, who underwent colonoscopy due to any reason between 2016 and 2018, were consecutively enrolled. PanMayo, MES, UCEIS and Dublin scores and additionally the Nancy histology score (where available) were recorded with clinical and demographical data at baseline. Disease flare, need for change in therapy (incl. initiation of biologicals, need for systemic steroids), hospitalisations and colectomy were tracked amongst patients with clinical remission (pMayo<2) during an at least 3-years follow-up to assess predictive value of score systems. Log-rank, Cox regression analysis and Chi2 tests were used to analyse outcomes and Kaplan Meier curves were plotted. Results A total of 250 UC patients (male ratio: 0.45, median age 45 (IQR) 22.3 years) were enrolled with 156 (male ratio 0.49; mean age 46 IQR 20.8 years, Table 1.) of UC patients having baseline clinical remission. PanMayo, MES, and Dublin scores were positively associated with risk of disease flare (Figure 1.; p=0.002, p<0.01, p=0.003). Increasing MES score was coupled with risk of relapse (MES0=26.7%, MES1=53.1% and MES2-3=47.6%; p=0.008). PanMayo score (above 12 points), but not MES or UCEIS, was associated with the need of new biological (Figure 2.; 66.7% vs. 21.7%; p<0.001) and treatment escalation (33.3 vs. 11.5%; p=0.018), similar trend was found for the Dublin score for need for new biologicals. There was a strong trend for PanMayo to predict need for hospital admission (p=0.06). All scores were strongly associated with need for systemic corticosteroids. Colectomy rates were low. Nancy score showed only a trend to predict risk of clinical flare and need for corticosteroids. Conclusion Our study suggests that combined endoscopic assessment of the extent and severity may be more accurate in predicting disease outcomes in UC in clinical remission. PanMayo scores may be an alternative of the existing scoring system and was associated more granularly with disease outcomes. In addition, outcomes were different in patients with initial MES 0 and 1 scores.

P647 Outcomes following the use of vedolizumab first line versus second line in Ulcerative Colitis: a single centre experience

Abstract Background With the introduction of an increasing number of biological therapies for Ulcerative Colitis (UC), decisions regarding the sequencing of treatment continues to dominate current management strategies. In this single centre study, we assessed outcomes in patients with UC following first line treatment with the α4β7 integrin blocker vedolizumab (VDZ) therapy vs second line VDZ therapy following anti-Tumour Necrosis Factor (anti-TNF) exposure. Methods All patients exposed to VDZ either first line or second line were identified via our Inflammatory Bowel Disease (IBD) registry. Data was collected retrospectively between June 2015 and June 2021. Baseline demographics, disease extent and activity scores, treatment continuation, and colectomy rates were analysed over a 52-week period. Results A total of 100 patients were included in the study, age (median [IQR]) 52 [37-64] years; 52% male 48% female). VDZ as first line biologic included 38 patients, age (median [IQR]) 51 [34-65] years; 50% male and 50% female). The VDZ as second line (Ant-TNF exposed) group included 62 patients, age (median [IQR]) 52 [38-61] years; 53% male and 47% female). The Anti-TNF exposed group included infliximab 26 (43.3%), adalimumab 22 (35.5%), golimumab 12 (19.2%) and both infliximab and adalimumab 2 (3%). Disease extent (Montreal classification: E1:proctitis, E2: left-sided or E3: extensive disease) in the VDZ first line group (E1 (13.1%), E2 (61.6%) and E3 (26.3%)) versus VDZ second line (E1 (11.3%), E2 (61.3%) and E3 (27.4%)). In the VDZ first line group (38 cases), the outcomes at 52 weeks were: Treatment continuation 24 (63%), colectomy 2 (5%) and treatment switch in 12 (32%) to infliximab (4), Adalimumab (3), Ustekinumab (4) and Tofacitinib (1). In comparison, the Anti-TNF exposed group (62 cases) outcomes at 52 weeks were: Treatment continuation 46 (74%), colectomy 5 (8%) and treatment switch in 11 (18%) to Adalimumab (2), Ustekinumab (4) and Tofacitinib (5). A total of 7 of patients underwent colectomy during the 52 week follow up period. By 52 weeks, 94.8% (36/38) were colectomy free in the VDZ first line group versus 92% (57/62) in the anti-TNF exposed group, which was not statistically significant (odds ratio (OR) of having a colectomy in the VDZ1st line group vs the VDZ 2nd line group was 0.61(p=0.58)). Conclusion Our study evaluated real-world treatment continuation and colectomy-free outcomes for VDZ as first and second line biologic therapy (Anti-TNF exposed) in patients with ulcerative colitis and confirmed its effectiveness in both treatment groups.

OP12 Does early initiation of biologics change the natural history of IBD? a nationwide study from the epi-IIRN

Abstract Background Studies have reported conflicting findings regarding the effect of timing of biologics initiation on disease course, often affected by selection and referral biases. In this nationwide cohort study we aimed to explore whether early initiation of biologics is associated with better disease outcomes in CD and UC. Methods Data of patients diagnosed with IBD in the epi-IIRN cohort from 2005 to 2020 were retrieved from 4 Israeli Health-Maintenance-Organizations covering 98% of the population.The primary analysis was time to steroid-dependency and IBD-related surgery. To control for confounding by indication in which the severity of disease could account both for the timing of biologics and risk of disease outcomes,we compared treatment strategies using the cloning,censoring and weighting method to emulate a target trial. Inverse probability of treatment weights were fitted per patient to adjust by weighting for time varying confounding and selection bias.Survival probabilities(POS) were estimated and compared at 10 years post diagnosis for each strategy through weighted non-parametric Kaplan-Meier estimators. The 95%CIs for survival probabilities were calculated using non-parametric bootstrap with 500 replicates. Results Of the 34,375 patients diagnosed with IBD, 7,452(39%) CD patients and 2,235(15%) UC patients received biologics and included in the analysis. In total,1,139 CD and 206 UC patients received biologics during the first three months after diagnosis,2,108 CD and 450 UC during the 3-12 month period,1,161 CD and 396 UC during 1-2 year period,and 719 CD and 271 UC during 2-3 years post diagnosis. Patients who initiated biologics after 3 years post diagnosis were excluded as they were not considered early biologics initiation.In CD,at 10 years post diagnosis there was a significant but modest decrease in IBD-related surgeries when initiating biologics prior to 3 months compared to the other periods (POS:0-3 months 0.75[CI 0.71- 0.79] vs 2-3 year 0.7[CI 0.66-0.73] ;p<0.05).The same observation with a larger effect, was apparent for steroid-dependency (POS:0-3 months 0.78[CI 0.75-0.82] vs 2-3 year 0.69[CI 0.66-0.71]; p<0.001)(Fig 1). In UC, no significant differences in colectomy rate at 10 years was observed between the treatment periods (POS:0-3 months 0.92[CI 0.87-0.97] vs. 2-3 years 0.94[CI 0.91-0.98];p=0.42). On the other hand, a significant decrease was apparent for steroid-dependency (POS:0-3 months 0.78[CI 0.75-0.82] vs 2-3 year 0.69[CI 0.66-0.71];p<0.001)(Fig 2). Conclusion Our study showed a slight advantage to earlier initiation of biologics,as reflected by longer time to IBD-related surgery and steroid-dependency in CD.In UC, the effect of early biologics was minor and was only apparent for steroid dependency in UC.

P778 Effectiveness and safety of a second-line rescue therapy for acute severe ulcerative colitis refractory to infliximab or ciclosporin (REASUC study)

Abstract Background The advent of new therapeutic agents and the improvement of supporting care might change the management of acute severe ulcerative colitis (ASUC) to avoid colectomy and change the natural history of the disease. The effectiveness and safety of sequential treatment should be evaluated in this scenario. Main aim To evaluate colectomy-free survival in patients with ASUC refractory to intravenous steroids who had failed infliximab (IFX) or ciclosporin (CyA) and received a second salvage therapy. Secondary aims: To evaluate the short-term and long-term effectiveness and to assess the safety of this strategy. Methods Multicentre study of patients admitted with ASUC refractory to corticosteroids who failed CyA or IFX and had received a second salvage therapy during the same hospital stay. Clinical activity was classified based on partial Mayo score and Lichtiger activity index. Patients who stopped second-line therapy due to disease activity or adverse events were considered as failures. Short-term colectomy-free survival was assessed by logistic regression analysis while long-term colectomy-free survival was evaluated by Kaplan-Meier curves and Cox regression models. Results Results: A total of 78 patients from 24 centres were included. As first-line therapy, IFX was administered to 32 patients, and CyA to 46. Baseline characteristics are detailed in table 1. The prescribed salvage therapy was IFX in 45 patients, CyA in 17, tofacitinib in 13, and ustekinumab in 3 (Figure 1). Colectomy was required in 29 patients (37%) during the follow-up (median 14 days, IQR 3-23). Colectomy-free survival curves are shown in figure 2-A and 2-B. Second-line salvage therapy with CyA was associated with a higher rate of colectomy (Figure 2-C). A total of 39 patients (55%) at week 12 and 20 patients (33%) at month 12 had clinical response; 31 patients (44%) at week 12 and 18 (30%) at month 12 were in clinical remission. At the last visit of the study, 26 patients (33%) were still under the second-line therapy. Adverse events (AE) were recorded in 26 patients (33%), being serious in 15. Resolution with no sequelae was observed in 20 patients (77%). No differences in AE between the second-line therapies prescribed were observed. There were two deaths: one due to cerebral thrombophlebitis and another due to bacteriemia after colectomy, both when CyA was the salvage therapy prescribed (Table 2). Conclusion A second-line salvage therapy avoids colectomy in a considerable percentage of patients admitted by ASUC and therefore it could be considered after IFX or CyA failure. The individual therapeutic approach must be discussed with patients due to the risk of serious adverse events.

P793 Infliximab and prevention of colectomy in acute severe ulcerative colitis: an individual patient data meta-analysis

Abstract Background Infliximab (IFX) is used to treat patients with acute severe ulcerative colitis (ASUC) who fail to respond to intravenous corticosteroid therapy. Yet, a significant proportion of patients does not respond adequately and requires colectomy. Our aim was to explore baseline predictors of colectomy-free survival during IFX rescue therapy in patients with steroid-refractory ASUC. Methods We performed an individual patient data meta-analysis (IPDMA) with data retrospectively collected from hospitalised, corticosteroid-refractory patients diagnosed with ASUC (based on Truelove and Witts’ criteria) who received IFX rescue therapy. Baseline characteristics including sex, smoking status, disease extent, disease duration, Mayo endoscopic subscore, serum albumin, C-reactive protein, haemoglobin, and white blood count were evaluated as predictors of colectomy-free survival at three and twelve months after start of IFX therapy. Data were analysed using R software (v4.2.0). Results Data were collected from six centres contributing a total of 140 patients (Table 1). Fifteen patients (10.7%) required colectomy within three months and another eight patients underwent colectomy by one year (total colectomy rate after one year 16.4%) (Figure 1). No baseline predictors of colectomy-free survival were identified (log-rank P>0.05). Patients who received intensified IFX induction therapy (n=64, >5 mg/kg), in contrast to patients on regular induction doses of 5 mg/kg at weeks 0-2-6 (n=49), did not have lower rates of colectomy. A total of 53 IFX serum trough concentrations (TC) were measured in 31 patients. The median IFX TC during weeks (w)1-2 of therapy was 13.5 mg/L (interquartile range [IQR] 9.3-16.3 mg/L), and 7.0 (IQR 1.9-12.0) mg/L during w3-6. Target attainment rates were 8.3% (1/12 patients) and 18.2% (2/11 patients), respectively, towards the previously reported IFX TC targets of 28.3 mg/L at w2 and 15.0 mg/L at w6 for achieving endoscopic remission at w12.1 IFX TCs during induction were not significantly different between patients who received standard and intensified induction therapy. Conclusion Colectomy rates remain a significant burden of ASUC even for patients receiving IFX. In our interim IPDMA, we did not identify baseline predictors of colectomy-free survival. Poor target attainments of the previously established concentration targets demand dose optimisation. Pharmacometrics modelling of the IFX dose-exposure-biomarker/measure-response relationship within the spECTRUM consortium (DEFINE study) will facilitate dose-finding simulations to demonstrate the value of model-informed therapeutic drug monitoring.

P780 Prognosis and optimal treatment for 5-aminosalicylic acid-intolerant patients with Ulcerative Colitis

Abstract Background 5-aminosalicylic acid (5-ASA) is widely used as a first-line treatment for ulcerative colitis (UC), but intolerance sometimes occurs. 5-ASA-intolerance was considered a risk factor for colectomy in UC patients, but no reports have examined which treatment is suitable to avoid colectomy in 5-ASA-intolerant UC patients. This is the first report describing a treatment strategy for 5-ASA-intolerant UC. The aims of this study were to determine the optimal therapeutic strategy in 5-ASA-intolerant UC patients. Methods This retrospective cohort study involved patients who were newly diagnosed as having UC after January 2010 and who received oral 5-ASA agents. Patients were considered 5-ASA-intolerant when they fulfilled two or more of the following conditions: (1) paradoxical aggravation of colitis on introducing oral 5-ASA agents or allergic reactions to the agents; (2) obvious improvement of abdominal symptoms after discontinuation of 5-ASA agents; (3) positive drug-induced lymphocyte stimulation test (DLST) for at least two formulations of 5-ASA; (4) adverse events following re-challenge with 5-ASA agents; and (5) severe adverse events owing to 5-ASA agents. Results Of 950 UC patients with a history of 5-ASA administration, 213 (22.4%) were considered 5-ASA-intolerant. Five-year colectomy-free survival was significantly lower in 5-ASA-intolerant patients compared with 5-ASA-tolerant patients (73% vs. 84%, respectively). From the multivariate Cox proportional hazards model analysis in the 5-ASA-intolerant patient cohort, thiopurine use was shown to contribute to avoidance of colectomy in 5-ASA-intolerant patients (hazard ratio = 0.25; 95% confidence interval, 0.13–0.47; P < 0.001); however, 5-ASA-intolerant patients were also likely to be thiopurine-intolerant compared with 5-ASA-tolerant patients (27% vs. 15%, respectively; P = 0.04). Calcineurin inhibitor use was associated with an increased risk of colectomy (hazard ratio = 4.80; 95% confidence interval, 2.24–10.3; P < 0.001), while treatment with systemic corticosteroids and biologics did not affect the colectomy rate (hazard ratio = 1.07; 95% confidence interval, 0.60–1.91; P = 0.81). Conclusion Treatment with thiopurines demonstrated the potential to improve the prognosis in 5-ASA-intolerant patients. However, it should be noted that thiopurine intolerance was more frequent in 5-ASA-intolerant patients. Compared to biologics, calcineurin inhibitors may not contribute to avoidance of colectomy, and biologics may be preferred for intractable patients with 5-ASA intolerance. This is the first report describing a treatment strategy for 5-ASA-intolerant UC, and we believe it will have many implications in clinical practice.

Fecal Microbiota Transplantation.

Fecal microbiota transplantation (FMT) is the process of transplanting stool from a healthy donor into the gut of a patient for therapeutic purposes. Current guidelines recommend FMT for the prevention of multiply recurrent Clostridioides difficile infection (CDI) after two recurrences, with cure rates approaching 90%. Emerging evidence also supports the use of FMT in the management of severe and fulminant CDI, resulting in decreased mortality and colectomy rates compared with standard of care approach. FMT shows promise as salvage therapy for critically-ill, refractory CDI patients who are poor surgical candidates. FMT should be considered early in the clinical course of severe CDI, preferably within 48 hours of failing to respond to antibiotic therapy and volume resuscitation. Besides CDI, ulcerative colitis was more recently identified as a potential treatment target for FMT. Several live biotherapeutics for microbiome restoration are on the horizon.

Colectomy rates in ulcerative colitis: A systematic review and meta-analysis.

Surgical management in Ulcerative Colitis (UC) is typically utilised in medically refractory cases and, therefore, it is a useful marker for efficacy of medical management. To understand the changing prevalence of colectomy in UC over time. A systematic review was conducted using MEDLINE (1946-2021), EMBASE and EMBASE classic (1947-2021) to identify studies with a population of n>500 that reported colectomy rates in UC patients >18 years old. The primary outcome was the prevalence of colectomy at 1-, 5- and 10-years post-diagnosis. Secondary outcomes included colectomy rates in the pre-biologics (defined as pre-2004) and post-biologics eras (defined as post-2004). Thirty-one studies with 294,359 patients with UC were included for review and meta-analysis. The prevalence of colectomy at 1-, 5- and 10-years post-diagnosis were 3% (95% CI 2%-6%), 5% (95% CI 2%-9%), 10% (95% CI 6%-16%) respectively. The pooled relative risk for colectomy in the post-biologics era was 0.68 (95% CI 0.42 to 1.09, p=0.10) at 1-year and 0.71 (95% CI 0.56 to 0.91, p<0.01) at 5-years post-diagnosis. The overall colectomy rate has decreased over the past three decades. Biologics may have played a role in reducing the risk of colectomy, however the relative risk reduction is likely to be modest.

Colectomy rates for ulcerative colitis over time: Navigating the evidence in the era of precision medicine and individualised treatment

Nick Dai and colleagues [1] conducted an up-to-date review of the literature to assess the rates of colectomy for ulcerative colitis (UC) over time, also comparing the pre-biologic vs biologic drug eras. Indeed many clinicians and their patients hoped that biologics would reduce, or even eliminate, the need for surgery,1 and whilst a reduction in colectomy rates occurred, the effect is smaller than expected.

Long-term Colectomy Rates of Ulcerative Colitis over 40 Years of Different Therapeutic Eras-Results from a Western Hungarian Population-based Inception Cohort Between 1977 and 2020.

Few populaion-based studies have investigated the long-term colectomy rates of ulcerative colitis [UC]. We aimed to assess the colectomy rates over 40 years of different therapeutic eras in a prospective population-based inception cohort from Veszprem Province, Western Hungary. Patient inclusion lasted between January1, 1977, and December31, 2018. Patient follow-up ended December 31, 2020. Colectomy rates and disease course were examined in three different eras based on the time of UC diagnosis; cohort A [1977-1995], cohort B [1996-2008], and cohort C [2009-2018]. A total of 1370 incident UC patients were included [male 51.2%, median age at diagnosis 37 years]. Median follow-up was 17 years (interquartile range [IQR] 9-24); 87 patients [6.4%] underwent colectomy. The cumulative probability of colectomy in the total population was 2.6% (95% confidence interval [CI] 2.2-3.0), 4.2% [95% CI 3.6-4.8], 7.0% [95% CI 6.2-7.8], and 10.4% [95% CI 9.1-11.7] after 5, 10, 20, and 30 years, respectively. The proportion of extensive colitis at diagnosis increased over time [24.2%/24.3%/34.9% in cohorts A/B/C, respectively, p = 0.001]. Overall exposure to immunomodulators [11.3%/20.9%/34.4% in cohorts A/B/C, respectively, p <0.001], as well as the probability for biologic therapy initiation increased over time (0%/3.3% [95% CI 2.6-4.0]/13.9% [95% CI 12.1-15.7], p <0.001). There were no statistically significant differences in the cumulative probability of colectomies between cohorts A/B/C: 1.7% [95% CI 1.0-2.4], 2.5% [95% CI 1.9-3.1], and 3.7% [95% CI 2.7-4.7] after 5 years; 3.5% [95% CI 2.5-4.5], 4.2% [95% CI 3.4-5.0], and 4.5% [95% CI 3.3-5.7] after 10 years; and 7.5% [95% CI 6.1-8.9] and 6.3% [95% CI 5.2-7.4] in cohorts A/B after 20 years [log-rank = 0.588]. Extensive colitis (hazard ratio [HR] 2.24, 95% CI 1.55-3.23) and continuous active disease activity [HR 6.36, 95% CI 3.46-11.67] were independent predictors for colectomy. No differences in colectomy rates have been observed in the incident UC patients over 40 years despite increasing use of immunomodulators and biologic therapies.

CO93 Rates of Disease-Related Hospitalization and Colectomy in Real-World Patients With Ulcerative Colitis on Anti-Tnf Agents: Evidence From a Systematic Review

Anti-TNF agents (ATAs) are generally the first-line biological therapy in ulcerative colitis (UC) patients who have failed treatment with corticosteroids and/or immunomodulators. Patients with non-response/loss of response with ATAs undergo treatment switch or colectomy/surgery. We assessed the rates of UC-related hospitalization and colectomy among patients on ATAs in real-world UC patients.

Dose-Intensified Infliximab Rescue Therapy on Short-term Colectomy Rates in Patients With Severe Ulcerative Colitis.

Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang City, Liaoning Province, China

Long-term outcomes of patients with acute severe ulcerative colitis treated with cyclosporine rescue therapy

Background and aims The early outcomes of ulcerative colitis (UC) after rescue therapy with cyclosporine A (CyA) are well known. Published data on the safety of this treatment in perioperative use and data on the long-term prognosis are scarce and are investigated here. Methods All UC patients treated with CyA in Tampere University Hospital between 2009 and 2018 were reviewed from patient records. Results A total of 182 patients were included with the median follow-up of 3.8 (range 0-13) years. Of all patients, 139 (76%) responded to CyA. A quarter of the responders achieved long-term remission and used thiopurines as maintenance therapy at the end of follow-up. Altogether 83 (46%) needed further enhancement of treatment with corticosteroids (Cs) and 57 (31%) with biologicals or small molecules. Of the nonresponders 27 (55%) were treated surgically within admission to index flare. Infliximab was used as a third-line rescue therapy for 16 patients of whom four benefitted. The overall colectomy rate in this series was 45%. When compared to Cs alone CyA did not increase the risk for severe postoperative complications in patients treated for severe treatment-refractory UC. Conclusion In conclusion, despite the good initial response to CyA, a large proportion of patients relapsed during long-term follow-up and the colectomy rates remain high. Other therapy attempts after failure of CyA merely postpone surgery in many. We therefore recommend informing patients about the possibility of surgery prior to the initiation of rescue therapy.

S990 Cost Analysis of Inpatient Originator Infliximab (Remicade) vs Biosimilar Infliximab (Renflexis) for Acute Severe Ulcerative Colitis: A Cost Minimization Study

Introduction: Infliximab (IFX) is a standard, inpatient salvage therapy for treatment of refractory acute severe ulcerative colitis (ASUC). Inpatient IFX, as the originator Remicade, significantly increases colectomy-free survival in this population. The biosimilar Renflexis offers reduced cost as compared to Remicade. We performed a cost-minimization analysis to compare costs with Remicade and Renflexis for inpatient treatment of ASUC. Methods: Retrospective clinical and financial data was obtained from 34 inpatients with refractory ASUC who had received treatment with Renflexis (17) or Remicade (17) between 2019-2021. Clinical data included admission and discharge serum albumin (alb), hemoglobin (Hgb), C-reactive protein (CRP), and colectomy rate within 30 days of treatment (CR-30). Financial data included a decision support drug cost (DSDC), depicting the total cost associated with inpatient infliximab administration, and total inpatient care cost, depicting the full cost of the inpatient admission. The following equation generated a ratio (rDSDC) which represents the percentage of how much the DSDC accounts for the total inpatient care cost, after controlling for dose of infliximab and length of stay. [DSDC of IFX/Number of Units of IFX] ÷ [Total Inpatient Cost of Care/Length of Stay in Days] Mean and unpaired T-test (parametric test) were used for clinical data analysis. Median and non-parametric test called Wilcoxon ranked sum test were used for financial data analysis. (Figure) Results: No differences were found in baseline or discharge clinical parameters including baseline CRP (P=0.64), alb (P=0.1294), Hgb (P=0.5051), discharge CRP (P=0.1244), alb (P=0.8728), Hgb (P=0.4875), or CR-30 (23.53% vs. 29.41%, p=0.6975) (Table). Median rDSDC was 0.387 vs. 0.241 in the Remicade vs. Renflexis groups, respectively (Figure, p = 0.0025) representing a difference of ∼14%. Conclusion: A 14% reduction in cost attributed to DSDC was found using Renflexis, as compared to Remicade, treating inpatient ASUC. Our calculation included median decision support drug cost as a percentage of the total inpatient care cost, controlling for dose of infliximab and length of stay. Such a reduced cost structure promotes use of Renflexis for ASUC inpatients, which may result in improved utilization, improved health outcomes, and reduced costs for patients and hospitals. Further studies may confirm non-inferiority and demonstrate cost-effectiveness.Figure 1 Table 1. - Remicade (n=17) Renflexis (n=17) P- Value Admission C-reactive protein 117.73 mg/L 103.98 mg/L 0.6400 Albumin 2.74 g/dL 2.45 g/dL 0.1294 Hgb 11.34 g/dL 10.82 g/dL 0.5051 Discharge C-reactive protein 17.18 mg/L 30.99 mg/L 0.1244 Albumin 2.36 g/dL 2.4 g/dL 0.8728 Hgb 10.11 g/dL 9.71 g/dL 0.4875 Colectomy rate within 30 days of Treatment 23.53% (n=4) 29.41% (n=5) 0.6975 Median ratio of decision support drug cost to total inpatient cost of care after accounting for number of units of IFX administered and length of inpatient stay in days 0.387 0.241 0.0025

S186 Variation in Colectomy Rates in Ulcerative Colitis

S186 Variation in Colectomy Rates in Ulcerative Colitis

S808 Level and Change of CRP Are Associated With 30-Day Risk of Colectomy in Patients Hospitalized With Acute Severe Ulcerative Colitis Receiving Infliximab

Introduction: Infliximab (IFX) has been efficacious in reducing colectomy rates among patients with moderate-to severe ulcerative colitis, but predictors of colectomy within 30 days of IFX among patients with acute severe ulcerative colitis (ASUC) are less established. Methods: We performed a single-center retrospective analysis of patients who received at least one dose of IFX while admitted between 2011-2022. We assessed demographic, clinical and laboratory predictors of colectomy within 30 days of first IFX dose. Multivariable and time-to-event analysis using Kaplan-Meier with log-rank statistics were used to assess risk factors for colectomy within 30 days. Results: A majority of the 172 patients hospitalized with ASUC who received IFX received 10 mg/kg (87.79%). Overall, 22/172 patients (12.79%) underwent colectomy within 30 days of first IFX dose. On univariable analysis, age, sex, race, ethnicity, BMI and smoking status were not associated with risk of colectomy. Higher initial CRP was significantly associated with 30-day risk of colectomy (106.17 vs. 65.10 mg/dL among patients who did not undergo colectomy; p< 0.01), as was a decrease of CRP ≤50% prior to discharge (p< 0.01). Lower initial albumin [< 3 (36.36%), 3.0-3.5 (40.91%), >3.5 g/dL (22.73%)] was associated with our primary outcome (p=0.046), as was a higher number of bowel movements in a 24-hour period prior to discharge (5.6 vs. 3.9 among patients who did not undergo colectomy; p=0.0256). On multivariable analysis, higher initial CRP (aOR 1.01, 95% CI 1.00 – 1.02), ≤50% change in CRP after first dose of IFX (aOR 9.00, 95% CI 2.43 – 33.29) and higher number of bowel movements in a 24-hour period prior to discharge (aOR 1.24, 95% CI 1.01– 1.52) remained significantly associated with risk of colectomy when adjusting for relevant covariables (Table). On Kaplan-Meier analysis, initial CRP >100 mg/dL, albumin < 3 g/dL and change in CRP ≤50% prior to discharge were significantly associated with decreased time to colectomy (Figure). Conclusion: Among patients with ASUC, higher CRP, decrease of CRP ≤50% and higher number of bowel movements prior to discharge were associated with increased risk of colectomy within 30-days of receiving IFX. Initial CRP >100 mg/dL, albumin < 3 g/dL and decrease of ≤50% in CRP prior to discharge were associated with decreased time to colectomy. These results can identify patients at highest risk and impact clinical decision-making regarding need for and timing of colectomy in patients with ASUC receiving IFX.Figure 1.: Kaplan–Meier curve showing estimates of proportion of patients requiring colectomy within 30 days of first infliximab dose (A) comparing patients with albumin on admission < 3 g/dL and albumin on admission ≥ 3 g/dL (p=0.0488) and (B) comparing patients with CRP on admission > 100 mg/dL and CRP on admission ≤ 100 mg/dL (p<0.01). Table 1. - Multivariable Analysis Examining Predictors of Colectomy within 30 Days Among Patients Hospitalized with Acute Severe Ulcerative Colitis Receiving Infliximab. *p=0.015; **p<0.01; ***p=0.036 Variable adjOdds Ratio (95% Confidence Interval) Disease Duration (years) 0.95 (0.86 – 1.04) Family history of IBD No Reference Yes 0.53 (0.10 – 2.79) Extent of disease on admission Proctitis/Left sided colitis Reference Not documented 0.13 (0.01 – 2.04) Pancolitis 1.30 (0.35 – 4.85) GI infection No Reference Yes 2.13 (0.51 – 8.91) CRP on admission (mg/dL)* 1.01 (1.00 – 1.02) Serum albumin on admission >3.5 g/dL Reference 3-3.5 g/dL 1.83 (0.47 – 7.12) < 3 g/dL 3.77 (0.79 – 18.07) Percent change in CRP after first infliximab dose** >50% decrease Reference ≤50% decrease 9.00 (2.43 – 33.29) Number of bowel movements in 24-hour period prior to discharge*** 1.24 (1.01– 1.52)