UC-related Hospitalization Research Articles

Comparison between tofacitinib and ustekinumab as a third-line therapy in refractory ulcerative colitis: A multicenter international study.

Ustekinumab and tofacitinib have recently been approved for the management of moderate to severe ulcerative colitis (UC). However, there is no evidence on how they should be positioned in the therapeutic algorithm. The aim of this study was to compare tofacitinib and ustekinumab as third-line therapies in UC patients in whom anti-TNF and vedolizumab had failed. This was a multicenter retrospective observational study. The primary outcome was disease progression, defined as the need for steroids, therapy escalation, UC-related hospitalization and/or surgery. Secondary outcomes were clinical remission, normalization of C-reactive protein, endoscopic remission, treatment withdrawal, and adverse events. One-hundred seventeen UC patients were included in the study and followed for a median time of 11.6months (q1-q3, 5.5-18.7). Overall, 65% of patients were treated with tofacitinib and 35% with ustekinumab. In the entire study cohort, 63 patients (54%) had disease progression during the follow-up period. Treatment with ustekinumab predicted increased risk of disease progression compared to treatment with tofacitinib in Cox regression analysis (HR: 1.93 [95% CI: 1.06-3.50] p=0.030). Twenty-eight (68%) patients in the ustekinumab group and 35 (46%) in the tofacitinib group had disease progression over the follow-up period (log-rank test, p<0.054). No significant differences were observed for the secondary outcomes. Six and 22 adverse events occurred in the ustekinumab and tofacitinib groups, respectively (15% vs. 31%, p=0.11). Tofacitinib was more efficacious in reducing disease progression than ustekinumab in this cohort of refractory UC patients. However, prospective head-to-head clinical trials are needed as to confirm these data.

P912 A Real-World Evidence Study of Dose Escalation and associated costs of advanced therapies for Ulcerative Colitis in France and United Kingdom

Abstract Background Dose escalation to optimize advanced therapies is common practice in ulcerative colitis (UC) to avoid intra-class or inter-class drug switching and maintain clinical response. Dose escalation also has impact on healthcare resource utilization (HRU) and costs. However, there are limited data available on real-life dose-escalation. Study aim was to understand real-world dose escalation/de-escalation UC advanced therapy drugs patterns in two European countries (France, United Kingdom [UK]). Methods This retrospective study analysed data from the THIN®/CEGEDIM database to identify adult patients with moderate-to-severe UC who were naïve to advanced UC therapies or had not received any of the UC advanced therapy drugs of interest (adalimumab [ADA], golimumab [GOL], infliximab [INF], tofacitinib [TOF], ustekinumab [UST], or vedolizumab [VED]) for at least 12 months prior first prescription (and/or dispensation for France) between January 2017 and February 2022. A dose increase of ≥20% during the maintenance period compared to lowest Summary of Product Characteristics recommended dose was considered dose escalation. Proportions of patients with dose escalation after maintenance date were estimated using Kaplan-Meier (KM) survival analyses. Clinical response (defined as absence of: UC-related hospitalization or colectomy, treatment switch or addition of another UC advanced drug, systemic/rectal corticosteroids exposure), and direct (consultations, hospitalisations, diagnostic tests, UC drugs, complementary therapy) and indirect costs related to UC by treatment cohort were also analysed. Results 1663 patients fulfilled the selection criteria, of whom 619 had information on dose patterns. Overall, 89% of patients (range 33% [INF] to 100% [GOL, TOF, and UST]) had dose escalation within the first 24 months after start of maintenance, with a median % dose increase ranging from +15% [VED] to +198% [GOL] (Table). Median (95% CI) time to first dose escalation was 2.1 (1.8-2.4) months (range 0.7 [UST] to 4.6 [VED]). Clinical response ranged from 56.3% (ADA) to 77.0% (INF). Direct annual HRU costs related to UC ranged from 3,085 (INF) to 16,527 (UST) EUR in France and from 1,857 (INF) to 4,104 (VED) GBP in the UK. Mean direct HRU costs in France were 25% higher in escalated patients compared to de-escalated patients (range: +4.2% GOL to +61.9% UST). Conclusion Dose escalation of advanced therapies for UC is a common strategy to avoid treatment-switching. Despite dose escalations and their cost to the system, a proportion of patients fail to achieve clinical response, highlighting the need for more efficacious and durable treatments for patients with moderate-to-severe UC.

P1054 Clinical outcomes for ulcerative colitis patients stopping 5-aminosalicylates starting biologics and/or immunomodulator therapy: A Systematic review and meta-analysis

Abstract Background Although 5-aminosalicylic acid (5-ASA), a crucial agent in the treatment of ulcerative colitis (UC), its role in the context of more advanced therapies, including immunomodulators and/or biologics, is not well defined. We sought to perform a systematic review and meta-analysis to assess the pooled consequences of discontinuing 5-ASA in patients with UC undergoing treatment with immunomodulators or biologics. Methods We searched MEDLINE, EMBASE, and the COCHRANE library to identify articles analyzing clinical outcomes associated with either discontinuing or maintaining 5-ASA in UC patients receiving immunomodulators or biologic treatments. A meta-analysis was performed using a random-effects model to pool estimates and report hazard ratios [HRs] or odds ratios [ORs], following the data format specified in the individual studies. Results A total of 6 studies were identified as eligible for the meta-analysis. In UC patients receiving immunomodulators and/or biologics, stopping 5-ASA was not associated with steroid use (HR 0.86, 95% confidence interval [CI] 0.65-1.14 and OR 0.84, 95% CI 0.47-1.51), UC-related hospitalization (HR 0.92, 95% CI 0.69-1.22), UC-related surgery (HR 0.88, 95% CI 0.65-1.18), one-year clinical (OR 0.93, 95% CI 0.63-1.39) and endoscopic (OR 1.24, 95% CI 0.30-5.08) remission. Conclusion The cessation of 5-ASA in UC patients treated with immunomodulators and/or biological agents is not related to worsening of clinical outcomes. This finding suggests a limited role for 5-ASA in the setting of more advanced therapies

P664 Anti-TNF exposure is associated with an increased risk of urgent and one-year colectomy in Acute Severe Ulcerative Colitis

Abstract Background Acute severe ulcerative colitis (ASUC) affects up to 25% of patients with UC and is significantly associated with an increased risk of colectomy. Despite improvements in medical management, individual patient prognostication and risk stratification in ASUC remains clinically challenging. We explored clinical, biochemical, and endoscopic factors as potential predictors for colectomy in patients hospitalized with ASUC. Methods A retrospective analysis of patients with ASUC as defined by Truelove and Witts criteria admitted to the Mount Sinai Hospital between 2011 and 2020 was conducted. Patients with well-documented data on disease history, medication use, clinical symptoms, and laboratory results during admission for ASUC were included. Colectomy risk during hospitalization and within one year was assessed. Multivariable logistic regression analyses were performed to identify clinical, biochemical, and endoscopic parameters associated with colectomy risk in patients with ASUC. Results Out of the 158 patients included, 34 (21.5%) underwent colectomy during hospital admission, and 41 (25.9%) within one year after admission. On multivariable analysis, adjusting for age, sex, body mass index (BMI), and disease duration, prior anti-TNF exposure (odds ratio [OR] 4.59, 95% confidence interval [CI] 1.57-13.4, P=0.005) and the use of biologics (any type) at admission (OR 3.31, 95%CI: 1.14-9.63, P=0.028) were associated with an increased risk of 1-year colectomy. Conversely, the use of mesalamines at admission was associated with a decreased risk of 1-year colectomy (OR 0.31, 95%CI: [0.13-0.72], P=0.006). Furthermore, recent UC-related hospitalization (within one year of admission) (OR 2.72, 95%CI: 1.15-6.43, P=0.022) and increased number of bowel movements after 3 days of treatment (OR 1.18, 95%CI: 1.04-1.34, P=0.011) were associated with higher risk of 1-year colectomy. Biomarkers measured at admission including hemoglobin and albumin were associated with a decreased risk, while CRP was associated with an increased risk of urgent and 1-year colectomy. Patients with deep ulcerations observed at endoscopy tended to have an increased risk of urgent colectomy, although this was not statistically significant (univariable OR 3.36, P=0.081). Finally, treatment of ASUC with anti-TNF was strongly associated with a decreased risk of urgent (OR 0.30, 95%CI: 0.13-0.73, P=0.007) and 1-year colectomy (OR 0.31, 95%CI: 0.14-0.73, P=0.007). Conclusion In patients with ASUC, anti-TNF treatment is associated with a reduced risk of both urgent and 1-year colectomy. Conversely a history of anti-TNF exposure is linked to a higher risk of both urgent and 1-year colectomy. This data emphasizes the need for alternative therapies.

HOSPITALIZATION, USE OF BIOLOGICS AND SURGERY RATES IN INFLAMMATORY BOWEL DISEASES: A SINGLE-CENTRE COMPARATIVE ANALYSIS BETWEEN PUBLIC AND PRIVATE HEALTHCARE SYSTEMS IN A TERTIARY UNIT FROM LATIN AMERICA.

Inflammatory bowel diseases (IBD) have rising incidence and prevalence rates globally. In IBD, there are scarce stu-dies comparing differences between patients according to 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. 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 systems. Demographic characteristics, hospitalizations, need for surgery and biologics were compared. A total of 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 surgery, 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%). There was no difference in UC-related hospitalizations between the subgroups (public 30.69% and private 37.66%) as well as the rates of colectomy (public: 16.83%, private: 19.48%). Biologics were prescribed almost twice as often in private as compared to public (45.45 vs 22.77%). There were no differences in the rates of hospitalization and abdominal surgery between the systems. In patients with UC, there was greater use of biological therapy in the private healthcare setting. • In a tertiary IBD center in Latin America. • More than half of the patients had been submitted to one or more CD-related abdominal surgical procedure. • Between the two healthcare systems, there was no difference in the rates of use of biological therapy in patients with CD, and in UC-related hospitalizations. • Biologics were prescribed almost twice as often in the private system as compared to the public in patients with UC.

Tofacitinib real-world experience in ulcerative colitis in Finland (FinTofUC): a retrospective non-interventional multicenter patient chart data study

Objectives The aim was to define the effectiveness of tofacitinib and to characterize the patient population receiving tofacitinib in a real-world cohort clinical setting for ulcerative colitis (UC) in Finland. Methods This is a retrospective non-interventional multicenter patient chart data study conducted in 23 Finnish Inflammatory Bowel Disease (IBD) centers. Baseline demographic and clinical data, clinical remission, steroid-free remission rate and time to tofacitinib discontinuation, colectomy or UC-related hospitalization were studied. Results The study included 252 UC patients of which 69% were male. Most patients had extensive disease (71%) and were bio-experienced (81%). Tofacitinib demonstrated positive treatment outcomes with clinical response, clinical remission, and steroid-free clinical remission at one year in 33%, 34% and 31% of patients, respectively. Moreover, 64% of patients in pMayo remission at week 16 from the start of tofacitinib were still in remission at one year. Only no or mild disease activity compared to moderate activity at baseline was associated with a higher probability of achieving remission according to pMayo at six months, p = .008. Hospitalizations and/or colectomies during the study period (before treatment discontinuation/end of follow-up) were low (n = 24), with less than 5 colectomies. Conclusions In this real-world cohort, including a majority of bio-experienced UC patients, tofacitinib was effective in achieving steroid-free clinical remission in a third of the population at one year. A majority of patients in remission at week 16 were also in remission at one year. Results are in line with earlier published real-world studies. Registration: ClinicalTrials.gov NCT05082428.

Healing of the epithelial barrier in the ileum is superior to endoscopic and histologic remission for predicting major adverse outcomes in ulcerative colitis.

Achieving endoscopic remission is a key therapeutic goal in patients with ulcerative colitis (UC) that is associated with favorable long-term disease outcomes. Here, we prospectively compared the predictive value of endoscopic and/or histologic remission against ileal barrier healing for predicting long-term disease behavior in a large cohort of UC patients in clinical remission. At baseline, UC patients in clinical remission underwent ileocolonoscopy with assessment of ileal barrier function by confocal endomicroscopy. Endoscopic and histologic disease activity and ileal barrier healing were scored using validated scores. During subsequent follow-up (FU), patients were closely monitored for clinical disease activity and occurrence of major adverse outcomes (MAO) defined as the following: disease relapse; UC-related hospitalization; UC-related surgery; necessity for initiation or dose escalation of systemic steroids, immunosuppressants, small molecules or biological therapy. Of the 73 UC patients included, 67% experienced MAO during a mean FU of 25 months. The probability of MAO-free survival was significantly higher in UC patients with endoscopic and/or histologic remission compared to patients with endoscopically and/or histologically active disease. Ileal barrier healing on endomicroscopy was highly accurate for predicting the further course of UC and outcompeted endoscopic and histologic remission for predicting MAO-free survival. Ileal barrier healing in clinically remittent UC patients can accurately predict future MAO development and is superior in its predictive capabilities than endoscopic and histologic remission. Ileal barrier healing therefore represents a novel and superior surrogate parameter for stratification of UC patients according to their risk for development of complicated disease behavior. https://classic.clinicaltrials.gov/ct2/show/NCT05157750, identifier NCT05157750.

Histologic Inflammation can Predict Future Clinical Relapse in Ulcerative Colitis Patients in Endoscopic Remission.

In ulcerative colitis (UC), endoscopic improvement, defined as a Mayo Endoscopic Score (MES) of 0 or 1, is a target of treatment. The aim of our study was to evaluate the risk of clinical relapse between patients with an MES of 0 or 1 and determine if histologic activity using the Robarts Histopathologic Index (RHI) was predictive of clinical relapse. UC patients with an MES score of 0 or 1, no prior colectomy, and at least 1 year of outpatient follow-up after colonoscopy were included. Demographic, clinical characteristics, and clinical relapse were retrospectively collected. Biopsy specimens were read by a gastrointestinal pathologist. Primary outcome was defined as a composite of relapse requiring change in medical therapy, new steroid use, UC-related hospitalization, and/or colectomy. Four hundred and forty-five UC patients were identified. Ninety-five percent of patients with MES 0 were in histologic remission by the RHI whereas only 35% of patients with MES 1 were in histologic remission. Twenty-six percent of patients experienced a clinical relapse; patients with MES 1 or RHI > 3 were significantly more likely to relapse (P < .01) compared to patients with MES 0 or RHI ≤ 3. When patients were stratified into 4 groups (MES 0, RHI ≤ 3; MES 0, RHI > 3; MES 1, RHI ≤ 3; MES 1, RHI > 3) and adjusted for age and sex, RHI > 3 was predictive of relapse (P = .008). UC patients with endoscopic improvement have a high rate of clinical relapse over time. Histologic activity is a predictor of clinical relapse.

A nationwide study of patients hospitalized with indeterminate colitis: a comparison with Crohn's disease and ulcerative colitis.

Indeterminate colitis (IC) is subtype of colonic inflammatory bowel disease (IBD) that has features of both Crohn's disease (CD) and ulcerative colitis (UC). There have also been no studies to date examining patients hospitalized with IC in the United States (US). We examined the demographic and clinical characteristics of patients admitted with IC and compared them with patients admitted with CD and UC. We also analyzed trends in cost and length of stay (LOS). Patients admitted with IC tended to be female (58%), Caucasian (72%), and younger [39 (SD: 23) years]. Patients with IC underwent lower endoscopy at higher rates (26%; CD: p < 0.001, UC: p = 0.08) but bowel surgery at lower rates compared to those with CD (11% vs. 16%; p = 0.04). Patients with IC were found to have a higher rate of bowel obstruction (4% vs. 0.7%, p = 0.004) than those with UC, but lower rates of abscess and obstruction compared to patients with CD (p < 0.001). When the analysis was confined to patients who underwent bowel surgery, IC patients still demonstrated higher rates of lower endoscopy (p = 0.03) but lower rates of abscess compared to CD patients (p = 0.049). Costs increased significantly over time for CD- and UC-related hospitalizations, but not for admissions related to IC. This is the first nationwide US study illustrating the demographics and clinical characteristics of patients hospitalized with IC. We conclude that IC has notable differences in hospitalization characteristics compared to the main two IBD subtypes.

P772 Association of histological remission with long-term clinical outcomes in patients with ulcerative colitis: a multi-national retrospective study with centralized histological assessment

Abstract Background Histological remission (HR) is an achievable therapeutic target in ulcerative colitis (UC), however there is limited data on the association of HR with long-term clinical outcomes. We evaluated the association between HR and a composite outcome of colectomy, UC-related hospitalization, or intravenous (IV) corticosteroid use in patients with UC. Methods This was a multi-national retrospective study of adult patients with UC treated with a biologic or small molecule drug between 09/01/2005 and 06/30/2019 in Canada, Italy, Netherlands and United States. The study included biologic-naïve (bio-naïve) and biologic-experienced (bio-exp) patients. Biopsies taken during routine practice were procured and re-assessed for histological activity by blinded gastrointestinal pathologists in a central laboratory. HR was defined as the absence of neutrophilic inflammation (Nancy Histological Index ≤1 or Robarts Histological Index ≤3 plus Geboes subgrades 2B.0/3.0) at the most recent endoscopic evaluation within 3 to 9 months after treatment initiation. Cumulative risk of time-to-event outcome over 12 months from treatment initiation was evaluated using Kaplan-Meier (KM) methods and Cox proportional hazard analysis. Statistical significance was set as p-value &amp;lt;0.05. Results We included 227 patients with UC (bio-naïve and bio-exp) (Table 1); of whom, 132 (58%) were bio-naïve (Table 2). Of the bio-naïve patients, 62 (47%) achieved HR and 70 (53%) had histologic activity; 9 (6.8%) underwent colectomy, 16 (12.1%) had UC-related hospitalizations, and 8 (6.1%) received IV corticosteroid. Unadjusted time-to-event for the composite outcome was significantly greater in bio-naïve patients who achieved HR compared to those who did not (p=0.0023; Figure 1A). In multivariable analysis, the association of HR on the composite outcome in bio-naïve patients was not statistically significant (adjusted hazard ratio [aHR], 0.26; 95% CI, 0.02-4.42). In the overall patients (bio-naïve and bio-exp), unadjusted (p&amp;lt;0.001; Figure 1B) and multivariable (aHR, 0.32; 95% CI, 0.06-1.75) associations of HR and the composite outcome were similar to the bio-naïve patients. Conclusion We used central reading to evaluate the association of HR and clinical outcomes in patients with UC. While unadjusted KM curves showed that HR was associated with decreased risk of the composite outcome, the association was no longer significant after adjustment for covariates. The target sample size for this study was not achieved and the number of events was small, resulting in reduced statistical power. Future studies are warranted to explore the association further.

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.

P122 External validation of the Picasso Histological Remission Index (PHRI) to assess endoscopic and histological remission and predict long-term outcome in Ulcerative Colitis: A multicentre prospective study.

Abstract Background The PICaSSO Histological remission Index (PHRI) is a simple histological index for assessing ulcerative colitis (UC) based only on the presence or absence of neutrophils in the lamina propria, superficial and cryptal epithelium (Table 1), which can be implemented in artificial intelligence (AI) systems.1 We aimed to externally validate its correlation with endoscopy and its prognostic value. Methods Patients with UC underwent colonoscopy in Birmingham, UK using white light+NBI, and in Milan, Italy, using white light+BLI/LCI. Participants were followed up for 2 years and occurrence of major adverse outcomes (UC-related hospitalization, UC treatment change/optimization, need for steroids, and colectomy) were recorded. We measured the correlation (Spearman coefficient) between histological scores (PHRI, Nancy [NHI] and Robarts [RHI]) and endoscopic scores (Mayo Endoscopic Score [MES]; Ulcerative Colitis Severity Endoscopic Index of Severity [UCEIS], and Paddington International virtual ChromoendoScopy ScOre [PICaSSO]). Vice versa, ROC curves were plotted for endoscopic scores to assess histological remission. Outcome analysis at 24 months was performed according to the Cochran-Mantel-Haenszel method, Kaplan-Meier curves were plotted and hazard ratios were calculated. Results 159 patients were enrolled, 79 in the NBI cohort and 81 in the BLI/LCI cohort. Demographic characteristics are detailed in Table 2. PHRI correlated with all endoscopic scores regardless of the type of virtual chromoendoscopy. In particular, in the NBI cohort correlations were 0.86, 0.83 and 0.81 for MES, UCEIS and PICaSSO, respectively; and 0.69, 0.65 and 0.58 in the BLI/LCI cohort. Correlation with endoscopy was also similar between PHRI, Nancy and Robarts. Table 3. The area under the ROC curve (AUROC) in the NBI cohort for MES, UCEIS and PICaSSO were 0.95 (95% CI 0.91-1.00), 0.95 (95% CI 0.90-1.00), and 0.93 (95% CI 0.87-0.99), respectively. Similarly, in the BLI/LCI cohort AUROCs were 0.86 (95% CI 0.78-0.94), 0.88 (95% CI 0.81-0.95) and 0.85 (95% CI 0.77-0.94). At survival analysis (Figure 1), Kaplan Meier curves appeared similar, and the hazard ratio (HR) between patients histologically active or in remission in the NBI cohort were 3.11 (95% CI 1.47-6.57), 2.93 (95% CI 1.36-6.32) and 2.19 (95% CI 1.07-4.53) for PHRI, RHI and NHI, respectively; and 2.82 (95% CI 1.54-5.15), 2.82 (95% CI 1.54-5.16) and 2.82 (95% CI 1.54-5.15) in the BLI/LCI cohort. Conclusion We confirmed PHRI’s correlation with endoscopy, its similar performance with RHI and NHI, and its prognostic value in two independent cohorts. Neutrophil-only assessment of UC is a simple reliable alternative to current histological scores and a useful tool for AI systems. Reference: 1 Gui X. et al. Gut, 2022

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, &amp;gt;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&amp;lt;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&amp;lt;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.

REAL-WORLD EXPERIENCE WITH TOFACITINIB DOSE DE-ESCALATION IN PATIENTS WITH MODERATE AND SEVERE ULCERATIVE COLITIS

Abstract BACKGROUND Tofacitinib is associated with sustained steroid-free remission and improved quality of life in patients with ulcerative colitis (UC), with the lowest effective dose recommended for maintenance therapy. However, there is limited real-world data to guide decision on optimal maintenance dose. We aimed to evaluate treatment outcomes of tofacitinib dose de-escalation in patients with UC in a real-world cohort. METHODS Included were adults with moderate-severe UC treated with tofacitinib between 1/2012-1/2022. Duration of treatment induction with 10 mg twice daily was 8, 16, or &amp;gt;16 weeks. Dose de-escalation was defined as decrease to 5 mg twice daily. Primary outcome was UC flare, defined as UC-related hospitalization/surgery, reinduction with tofacitinib dose increase, corticosteroid, or change of therapy class. Predictors of UC flare were explored using univariable and multivariable Cox regression. RESULTS Among 162 patients, 54% were male and 71% were white with a median age of 38 years, with 41% and 51% having moderate and severe UC, respectively. Eighty-three (52%) patients continued induction dose while 79 (48%) underwent dose de-escalation. There was no significant difference in number of prior biologic use or baseline endoscopic Mayo score, however, patients who underwent de-escalation were less likely to be steroid dependent during induction (50% vs 70%,p=0.01). After a median follow-up of 12 months, cumulative incidence rates of UC flare at 12 months were similar in patients with and without dose de-escalation (56% vs 58%,p=0.81), though patients without dose de-escalation had higher rates of UC-related hospitalization (27% vs 14%,p=0.04) and change of therapy class (39% vs 12%,p&amp;lt;0.01) compared to those who de-escalated. Among patients with dose de-escalation, cumulative rates of UC flare at 12 months were higher in patients with ongoing severe disease (Mayo 3) at 6 months of tofacitinib (Figure 1). In univariable Cox regression, prolonged duration of induction course with 10 mg twice daily &amp;gt;16 weeks was protective of UC flare (HR 0.37,95% CI 0.16-0.85) while ongoing severe disease (Mayo 3) was associated with UC flare (HR 6.41,95% CI 2.23-18.44), which remained significant after adjusting for age, sex, duration of induction course, and use of corticosteroid at dose de-escalation (HR 6.05, CI 2.00-18.35) (Table 1). Twenty-seven (29%) patients with UC flare had dose re-escalated to 10 mg twice daily with 63% recapturing clinical response at 12 months. CONCLUSIONS In this real-world cohort of UC patients with tofacitinib de-escalation, we observed a 56% cumulative incidence of UC flare at 12 months. Observed factors associated with UC flare after dose de-escalation included shorter induction course &amp;lt;16 weeks and active disease at 6 months of tofacitinib. The majority were able to recapture clinical response after dose re-escalation.

Clinical significance and long-term prognosis of ulcerative colitis patients with appendiceal orifice inflammation

BackgroundAppendiceal orifice inflammation (AOI) or peri-appendiceal red patch is a skip lesion with segments of continuous colitis from the rectum. Frequently observed in ulcerative colitis (UC) patients, this lesion might be associated with proximal extension in some studies. However, the clinical significance of this lesion and long-term outcomes including therapy remain unclear. Thus, the aim of this study was to evaluate the clinical implication of AOI during long-term periods in patients with UC.MethodsWe retrospectively reviewed 376 patients with UC who performed complete colonoscopic examinations between April 2000 and December 2020. We compared clinical characteristics and outcomes of patients manifesting AOI with those who did not show AOI during a mean follow-up period of 66.1 months. Long-term outcomes included maximal extent of colitis, proximal extension, therapeutic medical histories, UC-related hospitalization, and relapse.ResultsNinety-eight (26.1%) patients showed AOI without evidence of inflammation in the right colon. Mild disease activity at the diagnosis of UC was more included in patients with AOI than in those without AOI. Other baseline characteristics including disease extent, smoking history, external intestinal manifestation, and terminal ileal ulceration were not significantly different between the two groups. During follow-up periods, patients with and without AOI showed no significant difference in proximal extension, Mayo endoscopic score at the last endoscopic examination, UC-related hospitalization, or relapse. Of medication history, patients with AOI were less included in the group treated with high-dose aminosalicylates than those without AOI. However, therapeutic histories of steroids, immunosuppressive agents, and biologics were not significantly different. Of 62 patients with AOI who underwent follow-up colonoscopy, 36 (58.1%) showed resolution of AOI. Clinical outcomes of the resolution group were not different than those of the non-resolution group. Biopsy results of 77 patients with AOI showed chronic active or erosive colitis.ConclusionsLong-term outcomes of UC patients with AOI were not different from those without AOI. Outcomes of resolution and non-resolution groups of AOI patients were not different either. Thus, AOI might have no prognostic implication in distal UC patients.

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.

Ulcerative colitis progression: a retrospective analysis of disease burden using electronic medical records.

Ulcerative colitis (UC) is a debilitating inflammatory bowel disease. Present knowledge regarding UC disease progression over time is limited. To assess UC progression to severe disease along with disease burden and associated factors. Electronic medical records linked with Swedish national health registries (2005-2015) were used to identify disease progression of UC. Odds of all-cause and disease-related hospitalization within 1 year were compared between patients with disease progression and those without. Annual indirect costs were calculated based on sick leave, and factors related to UC progression were examined. Of the 1,361 patients with moderate UC, 24% progressed to severe disease during a median of 5.2 years. Severe UC had significantly higher odds for all-cause (OR [odds ratio] 1.47, 95% CI [confidence interval]: 1.12-1.94, P < 0.01) and UC-related hospitalization (OR 2.47, 95% CI: 1.76-3.47, P < 0.0001) compared to moderate disease. Average sick leave was higher in patients who progressed compared to those who did not (64.4 vs 38.6 days, P < 0.001), with higher indirect costs of 151,800 SEK (16,415 €) compared with 92,839 SEK (10,039 €) (P < 0.001), respectively. UC progression was related to young age (OR 1.62, 95% CI: 1.17-2.25, P < 0.01), long disease duration (OR 1.09, 95% CI: 1.03-1.15, P < 0.001), and use of corticosteroids (OR 2.49, 95% CI: 1.67-3.72, P < 0.001). Disease progression from moderate to severe UC is associated with more frequent and longer hospitalizations and sick leave. Patients at young age with long disease duration and more frequent glucocorticosteroid medication are associated with progression to severe UC.

S2701 Economic Costs and Trends in Inflammatory Bowel Disease-Related Hospitalizations and Surgery in the United States

Introduction: Limited data are available on hospitalization, surgery, and cost trends over time in patients with Crohn’s disease (CD) and ulcerative colitis (UC) in the United States. This analysis describes real-world trends in hospitalizations, surgery, and costs among patients with CD and UC. Case Description/Methods: Data from patients with CD and UC in the IBM MarketScan Databases (2007–2019) were evaluated. Eligible patients for each year had to have ≥1 inpatient claim or 2 outpatient claims for either CD or UC within that year and medical benefits for the entire year. For hospitalizations, an encounter group algorithm for all inpatient claims was utilized to determine the principal diagnosis and duration of each hospital episode. The surgery encounter was defined as either a hospitalization with a CD/UC-related surgery procedure code (principal procedure type) with a CD or UC diagnosis code in the first 2 diagnosis positions of the hospital encounter or an outpatient visit. Proportions of CD and UC patients with ≥1 hospitalization or surgery, the average cost per surgery or hospitalization episode, and mean length of stay (LOS) in days were reported for each year. Costs were adjusted to 2020 US dollars. Over time, prevalence of hospitalizations decreased from 11.8% and 7.7% in 2007 to 7.1% and 4.8% in 2019 in patients with CD and UC, respectively ( Figurea). The annual proportion of patients with a CD/UC-related surgery decreased from 2.3% and 1.2% in 2007 to 1.6% and 0.9% in 2019 in patients with CD and UC, respectively. Conversely, mean medical costs per CD/UC hospitalization episode increased from $22,346/$23,002 in 2007 to $28,586/$28,069 in 2019 (Figureb). Additionally, mean medical costs per CD/UC surgery increased from $41,300 and $47,286 in 2007 to $55,870 and $61,698 in 2019. In patients with CD and UC, the average LOS per hospitalization reduced from 5.8 and 6.6 days in 2007 to 4.6 and 5.6 days in 2019. Discussion: Despite a decrease in CD- and UC-related hospitalizations and surgery from 2007 to 2019, as well as reduced mean LOS, the average cost per hospitalization and surgery increased. Additional research is warranted to better understand these trends so that medical costs can be further reduced and management of patients in the outpatient setting can be improved.Figure 1.: Prevalence of (a) Hospitalization and Surgery and (b) Mean Costs by Year *Includes all associated costs except medication costs. CD, Crohn’s disease; K, thousand; UC, ulcerative colitis.

Ulcerative colitis: Impact of early disease clearance on long-term outcomes - A multicenter cohort study.

BackgroundClinical remission and endoscopic mucosal healing are the main treatment targets in patients with ulcerative colitis (UC). Recently, the concept of disease clearance has been proposed as a potential target in UC.ObjectiveWe aimed to evaluate the impact of disease clearance on long‐term outcomes in UC patients.MethodsA multicenter retrospective cohort study was conducted at the Humanitas Research Hospital‐IRCCS (Italy) and at the Nancy University Hospital (France) between 2014 and 2021. Disease clearance in UC was defined as simultaneous clinical (partial‐Mayo score ≤2), endoscopic (endoscopic‐Mayo score = 0), and histological (Nancy index = 0) remission, and patients were monitored over a long‐time follow‐up (≥12 months), to compare the occurrence of negative outcomes.ResultsA total of 494 patients with UC was included in the study (269, 54.4% males). Disease clearance was present in 109 patients (22.1%) at baseline. Median follow up was 24 months. Patients with disease clearance were associated to a significantly lower risk of UC‐related hospitalization compared with the control group (5.5% vs. 23.1%; p < 0.001) at last observation. Similarly, a lower rate of surgeries was detected in patients with disease clearance at baseline compared with those without (1.8% vs. 10.9%; p = 0.003). The Kaplan Meier curves confirmed that patients with disease clearance at baseline had a lower risk of hospitalization (log‐rank p < 0.0001) and surgery (log‐rank p < 0.00095).ConclusionIn UC patients with early disease clearance are at significant lower risk for hospitalization and surgery. Disease clearance should be considered as a new composite outcome.

Prognostic Value of Fecal Calprotectin to Inform Treat-to-Target Monitoring in Ulcerative Colitis

We evaluated the value of post-induction fecal calprotectin (FCP) concentration as a biomarker in patients with ulcerative colitis (UC) treated with a biologic. This post hoc analysis of the GEMINI 1/GEMINI LTS (N= 620) and VARSITY (N= 771) trials evaluated the cross-sectional accuracy of post-induction FCP in identifying endoscopic activity and histologic inflammation, and the prognostic performance of FCP in identifying patients most likely to achieve endoscopic and histologic remission or require colectomy and UC-related hospitalization. The cross-sectional accuracy of FCP in identifying endoscopic activity and histologic inflammation was modest (63%-79%). However, a post-induction FCP concentration of ≤250 μg/g vs >250 μg/g was associated with a substantially higher probability of achieving clinical remission (odds ratio [OR], 4.03; 95% confidence interval [CI], 2.78-5.85), endoscopic remission (OR, 4.26; 95% CI, 2.83-6.40), and histologic remission (Robarts Histopathology Index: OR, 5.54; 95% CI, 3.77-8.14; Geboes grade: OR, 6.42; 95% CI, 4.02-10.26) at week 52 and a lower probability of colectomy over 7 years (hazard ratio, 0.296; 95% CI, 0.130-0.677) and UC-related hospitalization (hazard ratio, 0.583; 95% CI, 0.389-0.874). The association with colectomy was significant even among patients in symptomatic remission or with endoscopic improvement post-induction, and among patients with elevated FCP at baseline. Although FCP had only modest cross-sectional accuracy in identifying disease activity, an FCP concentration of ≤250 μg/g vs >250 μg/g was associated with increased probability of achieving long-term clinical, endoscopic, and histologic remission, and reduced probability of colectomy and UC-related hospitalization (ClinicalTrials.gov: NCT00783718, NCT00790933, NCT02497469).