Colectomy Rates Research Articles

Comparative Effectiveness of Ozanimod and Vedolizumab as First-Line Advanced Therapies in Ulcerative Colitis: A Propensity-Matched Cohort Analysis.

There is limited real-world evidence comparing the effectiveness of ozanimod to vedolizumab as first-line advanced therapies in patients with ulcerative colitis (UC). We conducted a retrospective cohort study using TriNetX, a multi-institutional US database in adults with UC who were initiated on ozanimod compared to vedolizumab between January 1, 2021 and 22 June, 2024. The primary outcome was to compare the risk of a composite outcome of corticosteroid use, colectomy, or change to another advanced therapy between the 2 cohorts within 12 months. 1:1 propensity score matching (PSM) was performed for demographics, comorbid conditions, disease extent, laboratory parameters, and previous corticosteroid use. The risk was expressed as an adjusted odds ratio (aOR) with 95% CIs. We identified 222 patients in the ozanimod cohort (mean age 41.2 ± 15.7, 46.3% male sex, 68% White, and 22.5% ulcerative proctitis), and 4145 patients in the vedolizumab cohort (mean age 47.4 ± 18.3, 45.2% male sex, 69.7% White, and 17.2% ulcerative proctitis). After PSM, there was no significant difference in the risk of the composite outcome (aOR 0.92, 95% CI, 0.63-1.36) and corticosteroid use (aOR 0.80, 95% CI, 0.53-1.18) between the 2 cohorts within 12 months. There was a higher risk of change in therapy in the ozanimod cohort (aOR 1.95, 95% CI, 1.09-3.49) compared to the vedolizumab cohort. Colectomy rates were low in both cohorts (<0.04%). Our real-world study showed that ozanimod use is associated with similar corticosteroid use but higher odds of a change in therapy compared to vedolizumab when used as first-line therapy in patients with UC. Further prospective studies are needed to understand long-term outcomes.

Predicting Outcomes in Hospitalized Patients With Acute Severe Ulcerative Colitis in a Prospective Multicenter Cohort.

Acute severe ulcerative colitis (UC) (ASUC) requiring hospitalization affects up to 1 in 4 patients with UC. There is a paucity of prospective and multicenter clinical cohorts to study treatment trends and predictors of disease outcomes. Here, we conduct a US-based multicenter prospective clinical cohort of ASUC to study predictors of the need for medical rescue therapy and colectomy. A total of 94 patients hospitalized for ASUC were included across 5 academic centers from December 2018 to December 2021. Demographic, clinical, and laboratory data were collected throughout the hospitalization. Patients were followed up to 1-year post-hospitalization to identify predictors of the need for rescue therapy and colectomy. A total of 21 (22.3%) patients required colectomy within 1 year of admission with 11 (12%) requiring colectomy during the index admission. On multivariate analyses, a BMI < 21.5kg/m2 (OR = 6.16, P = .02), a simple clinical colitis activity index (SCCAI) greater than 8 (OR = 14.44, P = .01) and an albumin level at admission lower than 2.4g/dL (OR = 10.61, P = .04) were significant predictors of inpatient colectomy after adjusting for sex, age, and duration of disease. In a prospective, multicenter cohort of patients hospitalized with ASUC, BMI, SCCAI, and albumin at admission were important determinants of colectomy risk during the index hospitalization and within 1 year of admission. Colectomy rates remain high-22.3% in this cohort across 5 academic, tertiary care centers-underscoring the need to identify the highest-risk patients, establish novel treatment and care paradigms, and examine opportunities to standardize care.

Early treatment for Clostridioides difficile infection: retrospective cohort study.

Clostridioides difficile (CDI) is a common cause of infectious diarrhea. The current recommendation is to initiate empirical antibiotic treatment for suspected CDI who have an anticipated delay of confirmatory results or fulminant colitis. This is based on limited clinical trials. The study aims to examine the impact of early treatment on mortality and clinical outcomes. This retrospective cohort study included adult patients with CDI. Early treatment was defined as the initiation of an anti-Clostridioides medication within the first 24h following stool sampling. Outcomes were 30 and 90day mortality, length of hospital stay (LOS), recurrence, and colectomy rate. To address potential bias, propensity score matching followed by logistic regression was performed, P value less than 5% was considered statistically significant. Study cohort consisted of 796 patients; clinical characteristics were balanced following matching. There was no difference, in favor of early treatment, between the groups regarding 30day mortality and 90day mortality with HR of 0.91 (95% CI 0.56-1.47) and 0.7 (95% CI 0.45-1.08), respectively. No statistically significant difference in recurrence rate, ICU admission or colectomy rate was observed. The LOS was shorter in the early-treatment group with 6days vs. 8days. Early treatment for CDI had shortened hospital stay. However, it did not affect clinical outcomes in adult patients.

Clinical profile and short-term outcomes of acute severe ulcerative colitis in Vietnam: insights from a resource-limited setting.

Acute severe ulcerative colitis (ASUC) is a significant complication of ulcerative colitis, affecting roughly 25% of patients and increasing the risk of colectomy and hospital mortality. While intravenous steroids are a primary treatment, only 67% of patients respond, necessitating rescue therapy for non-responders. Data on ASUC in the Vietnamese population are scarce. This study aims to provide insights into the clinical characteristics and short-term outcomes of Vietnamese patients with ASUC. We conducted a prospective case series on ASUC patients admitted to the University Medical Center in Ho Chi Minh City from January 2021 to June 2023. Steroid response was assessed using the Travis Oxford criteria. We evaluated clinical features, in-hospital steroid response rates, endoscopic remission, and colectomy rates 12 months post-hospitalization. Seventeen patients with a median age of 42 years (70.6% male) were included. The median time from symptom onset to diagnosis was six weeks, and 47.1% had a history of ulcerative colitis. Median CRP value was 75.8 mg/L, and 76.5% had fecal calprotectin concentrations above 800 µg/g. All patients had a Mayo endoscopic subscore of ≥2, with 12.5% showing deep ulcers. Eleven patients (64.7%) responded to in-hospital steroid treatment, while 6 (35.3%) required rescue therapy with infliximab or tofacitinib. After one year, 10 of 11 (90.1%) achieved mucosal healing, and no patients underwent colectomy. Corticosteroids remain the cornerstone for initial ASUC therapy, though many patients do not respond. Anti-TNF agents and tofacitinib show potential benefits for those unresponsive to steroids. This study highlights the effectiveness of corticosteroids and biologics in managing ASUC in Vietnam.

A trend analysis of inflammatory bowel disease in non-endemic era (1993-2023)

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

Opioid Use and Outcomes in Patients Hospitalized With Acute Severe Ulcerative Colitis.

Opioid use has not been shown to improve hospitalized inflammatory bowel disease patient pain scores and may prolong the length of stay (LOS). Additional clinical implications of opioid use, particularly high amounts, in the hospital setting have not yet been explored. We sought to determine how high opioid use impacts clinical outcomes in acute severe ulcerative colitis (ASUC). In this single-center study, we identified all patients hospitalized with ASUC who received intravenous corticosteroids from July 1, 2014 to December 31, 2021. Clinical outcomes including opioid exposure, cumulative intravenous corticosteroid dose, biologic rescue therapy initiation date, colectomy rate, opioid prescription at discharge, LOS, and hospitalization cost were collected. High opioid use was defined as ≥40 oral morphine equivalents (OMEs) per day. A univariable logistic regression was performed to evaluate the association of high opioid use with ASUC outcomes. 185 eligible hospitalizations for ASUC were evaluated. 75 patients (41%) received opioids during hospitalization, and 20 patients (11%) received ≥40 OMEs/day. High opioid use was associated with a median 3-day delay in biologic rescue therapy initiation when compared with low/no opioid use (P = .02). 70% of patients with high opioid use received an opioid prescription at discharge compared with 10% of those with low/no use (P < .001). Opioid use was not associated with LOS, duration of corticosteroid therapy, colectomy rate, or hospitalization cost. Among ASUC hospitalizations, high opioid use was associated with delayed biologic rescue therapy initiation and higher rates of opioid prescriptions at discharge.

Splenic flexure adenocarcinoma: A national cohort analysis of extent of surgical resection and outcomes.

The optimal extent of resection for splenic flexure adenocarcinoma remains debated. These tumours straddle the left- and right-sided vasculature with lymphatic drainage in a watershed area; current guidelines recommend either segmental or extended colectomy. We analysed surgical management of splenic flexure tumours and compared outcomes between approaches. The Surveillance, Epidemiology and End Results database was searched for adults with Stage I-III splenic flexure adenocarcinoma, 2004-2019. Of 5238 patients, 55% underwent extended colectomy. Compared to segmental colectomy, these patients were more likely to have advanced stage. On multivariable analysis, age ≤ 65 years remained independently associated with extended colectomy. Although fewer nodes were examined in segmental colectomy (median 14 vs. 16, p < 0.001), the number of positive nodes (both, median 0 [interquartile ratio 0-2], p = 0.20) and the lymph node ratio were similar between cohorts. Surgical approach was not significantly associated with increased positive nodal yield in adjusted analyses. Five-year overall and disease-specific survival were 73% and 84% for segmental and 72% and 83% for extended colectomy (p > 0.4); these remained comparable after adjustment. Nationally, we observed similar rates of segmental and extended colectomy for splenic flexure adenocarcinoma. Extended colectomy was not more common in Stage III disease, indicating lack of stage migration, and was not associated with better oncological outcomes. These observations support current practice involving either approach, which should be tailored to patient-related factors and preferences, while considering technical aspects and quality of life.

Gastric Acid Suppression Is Associated with Higher Rates of Colectomy in Patients with Inflammatory Bowel Disease

Gastric Acid Suppression Is Associated with Higher Rates of Colectomy in Patients with Inflammatory Bowel Disease

Upadacitinib for Acute Severe Ulcerative Colitis: A Systematic Review.

Acute severe ulcerative colitis (ASUC) remains a clinical challenge associated with considerable morbidity, including colectomy. Upadacitinib (UPA), a selective Janus kinase (JAK)-1 inhibitor, is approved for moderate-to-severe ulcerative colitis in patients intolerant or not responding to tumor necrosis factor-alpha inhibitors. It has also increasingly been used off-label for ASUC. We performed a systematic review of all available literature on UPA in ASUC. We identified 11 studies, with a pooled total of 55 patients. Most patients experienced rapid and sustained improvement. Colectomy rate at 90 days was 16.3%. Among those who did not get colectomy, 80% were in steroid-free remission at follow-up. The reported adverse events were low, including 2 venous thromboembolic events. Overall, UPA appears to represent a safe and effective therapy for ASUC.

Evaluating the Efficacy of Infliximab in Inflammatory Bowel Disease: A Systematic Review of the Literature.

The introduction of steroid therapy in 1955 markedly decreased the mortality rate of severe ulcerative colitis (UC) from 24% in the placebo group to 7%, and it is currently less than 1% in specialist centers. Despite this advancement, the response of severe UC to steroids has stagnated over the past 50 years, with a high rate of colectomy persisting for severe to moderately severe cases. Infliximab (IFX) (Remicade, CentocorInc., Malvern, PA, United States), an intravenously administered chimeric monoclonal immunoglobulin G1 antibody targeting tumor necrosis factor-alpha (TNF-α), has shown efficacy in numerous randomized controlled trials for treating moderate to severe and fistulizing Crohn's disease, particularly in patients unresponsive to conventional therapies. This led to its approval by the US Food and Drug Administration in 1998 for treating active and fistulizing Crohn's disease. Most clinical research on IFX has focused on Crohn's disease, which is characterized as a Th1-type condition driven by pro-inflammatory cytokines like TNF-α. Conversely, UC has traditionally been viewed as a Th2-type condition where TNF-α plays a lesser role. However, recent studies indicate that TNF-α might also contribute to the pathogenesis of UC. These findings highlight the necessity for larger randomized controlled trials to further investigate the benefits of therapies like IFX, with the ultimate goal of improving treatment outcomes and quality of life for patients with inflammatory bowel disease.

Rescue Therapies for Steroid-Refractory Acute Severe Ulcerative Colitis: A Systemic Review and Network Meta-analysis.

Approximately 40% of patients with steroid-refractory acute severe ulcerative colitis (steroid-refractory (SR) ASUC) requires colectomies. Advanced therapies may reduce the short-term colectomy rates in patients with SR ASUC. However, comparative clinical studies evaluating the effectiveness of these rescue therapies are lacking. Therefore, we conducted a network meta-analysis to study the effectiveness of rescue therapies for SR ASUC. Six randomized controlled trials and 15 cohort studies including 2,004 patients were analyzed. Rescue drugs included tofacitinib, infliximab with a 5 or 10mg/kg induction dose at 0, 2, and 6 weeks (IFX and IFX10, respectively), IFX with an accelerated regimen of three 5mg/kg induction doses timed according to clinical need (accelerated IFX), tacrolimus, cyclosporine (CyA), ustekinumab, and adalimumab. Treatments were compared with a placebo. Tofacitinib (odds ratio [OR]: 0.09 [95% confidence interval [CI]: 0.02-0.52]), accelerated IFX (OR: 0.16 [95% CI: 0.03-0.94]), IFX (OR: 0.2 [95% CI: 0.07-0.58]), and tacrolimus (OR: 0.24 [95% CI: 0.06-0.96]) significantly reduced the short-term colectomy rates compared with placebo. IFX10 and CyA tended to prevent colectomies. However, ustekinumab and adalimumab did not significantly affect the colectomy rates. This is the first network meta-analysis to investigate the efficacy of advanced therapies in reducing short-term colectomy rates in patients with SR ASUC. Tofacitinib, accelerated IFX, standard IFX, and tacrolimus significantly reduced the colectomy rates in SR ASUC patients compared with placebo. Thus, advanced therapies should be considered for rescue therapies in patients with SR ASUC.

Intravenous Albumin Infusion Does not Augment the Response Rate to a Combination of Exclusive Enteral Nutrition and Intravenous Steroids in Acute Severe Ulcerative Colitis: A Randomised Controlled Trial.

Overall, 30-40% patients with acute severe ulcerative colitis [ASUC] fail intravenous [IV] steroids, requiring medical rescue therapy/colectomy. Low baseline albumin predicts steroid non-response, and exclusive enteral nutrition [EEN] has been shown to improve steroid response and albumin levels. Albumin infusion, due to its anti-inflammatory and antioxidant properties, might further improve steroid response in ASUC, which was evaluated in the present study. In this open-label, randomised, controlled trial, patients with ASUC were randomised in 1:1 ratio to either albumin + standard of care [SOC] + EEN [Albumin arm] or SOC + EEN [SOC arm], over January 2021-February 2023. Both arms received 5 days of EEN with 400 mg IV hydrocortisone/day. Patients in the Albumin arm were administered 5 days of 20% weight/volume [w/v] intravenous albumin [100 ml]. Primary outcome was first, steroid failure [need for rescue medical therapy or colectomy] and second, proportion of patients with adverse events. In all, 61 patients [albumin: 30, SOC: 31][mean age 31.6 ± 0.4 years, male 57.4%], were included. Baseline characteristics were comparable. There was no difference in steroid failure between Albumin and SOC arms (10/30 [33.33%] vs 13/31[41.94%], p = 0.49). No adverse events were reported with albumin infusions. Colectomy rate [10% vs 9.68%, p = 1], response to salvage medical therapy [88.89% vs 76.92%, p = 0.62] and median [interquartile range] duration of hospitalisation [10.5 [7-16] vs 10 [7-20], p = 0.43] were also comparable. The long-term composite outcome of colectomy and re-admission rates was numerically higher in the Albumin than the SOC arm [37.04% vs 17.86%, p > 0.05], although this did not reach statistical significance. There was no benefit of intravenous albumin infusion as an adjunct to IV steroids and EEN in patients with ASUC.

Clinical course of ulcerative colitis: Frequent use of biologics and low colectomy rate first year after diagnosis-results from the IBSEN III inception cohort.

The introduction of biologic therapies and the 'treat-to-target' treatment strategy may have changed the disease course of ulcerative colitis (UC). To describe the early disease course and disease outcome at 1-year follow-up in a population-based inception cohort of adult patients with newly diagnosed UC. The Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) III study is a population-based inception cohort study with prospective follow-up. Patients newly diagnosed with inflammatory bowel disease during 2017-2019 were included. Patients ≥18 years at diagnosis of UC who attended the 1-year follow-up were investigated. We registered clinical, endoscopic and demographic data at diagnosis and 1-year follow-up. We included 877 patients with UC (median age 36 years (range: 18-84), 45.8% female). At diagnosis, 39.2% presented with proctitis, 24.7% left-sided colitis and 36.0% extensive colitis. At the 1-year follow-up, 13.9% experienced disease progression, and 14.5% had received one or more biologic therapies. The colectomy rate was 0.9%. Steroid-free clinical remission was observed in 76.6%, and steroid-free endoscopic remission in 68.7%. Anaemia and initiation of systemic steroid treatment at diagnosis were associated with biologic therapy within the first year after diagnosis. In this population-based inception cohort, colectomy rate in the first year after diagnosis was low, and a high proportion of patients were in remission at 1-year follow-up. The use of biologic therapy increases, consistent with findings from previous studies.

Tofacitinib in Pediatric Ulcerative Colitis: A Retrospective Multicenter Experience.

Tofacitinib has recently been approved for treatment of moderate-to-severe ulcerative colitis (UC) in adults, yet pediatric data are limited. This international multicenter study describes the effectiveness and safety of tofacitinib in pediatric UC. This is a retrospective review of children diagnosed with UC treated with tofacitinib from 16 pediatric centers internationally. The primary outcome was week 8 corticosteroid-free clinical remission (Pediatric Ulcerative Colitis Activity Index <10). Secondary outcomes were clinical response (≥20-point decrease in Pediatric Ulcerative Colitis Activity Index) at week 8, corticosteroid-free clinical remission at week 24, and colectomy rate and adverse safety events through to last follow-up. The primary outcome was calculated by the intention-to-treat principle. We included 101 children with a mean age at diagnosis of 12.8 ± 2.8 years and a median disease duration of 20 months (interquartile range [IQR], 10-39 months). All had treatment failure with at least 1 biologic agent, and 36 (36%) had treatment failure with 3 agents. Median follow-up was 24 weeks (IQR, 16-54 weeks). Sixteen (16%) children achieved corticosteroid-free clinical remission at week 8, and an additional 30 (30%) demonstrated clinical response. Twenty (23%) of 88 children achieved corticosteroid-free clinical remission at week 24. A total of 25 (25%) children underwent colectomy by median 86 days (IQR, 36-130 days). No serious drug-related adverse events were reported; there was 1 case of herpes zoster and 2 cases of minor blood test perturbations. In this largest real-life pediatric cohort to date, tofacitinib was effective in at least 16% of patients with highly refractory UC by week 8. Adverse events were minor and largely consistent with adult data.

Outcomes of patients admitted with acute, severe ulcerative colitis on biologic therapy: a retrospective analysis from a tertiary referral hospital.

In steroid-refractory acute, severe, ulcerative colitis (ASUC), salvage medical therapy with infliximab is recommended to reduce the risk of colectomy. However, the evidence supporting this practice is based on cohorts naïve to biologics. Consequently, the management of patients on biologic or small molecule therapy (BST) with ASUC is not well defined. We conducted a retrospective chart review of patients admitted with ASUC to Mount Sinai Hospital (MSH) in Toronto, Ontario from January 2018 until January 2022. Included subjects were considered to be on BST if they had received a dose of these agents within 56 days prior to admission. Our outcomes of interest included the mean difference in hospital length of stay (HLOS), rates of surgical consultation, rates of inpatient colectomies, and 90-day readmission rates between the 2 groups. Of the 185 admissions for ASUC, 76 were on BST prior to admission and 109 were not. Baseline characteristics were similar between the 2 groups. There were no significant differences in hospital length of stay (7.46 days vs 7.45 days P = .52) or in-hospital colectomy rates between the 2 groups. Patients on BST had higher rates of surgical consultation (36.8% vs 8.3% P < .01) and 90-day readmission rates (26.3% vs 13.8% P = .03). We did not identify significant differences in the majority of our outcomes between the 2 groups. However, patients on BST were more likely to receive a surgical consultation during their admission and had higher rates of readmission at 90 days. Further studies evaluating the underlying factors that contribute to readmission in patients on BST in hospitals are needed.

Current Management of Acute Severe Ulcerative Colitis: New Insights on the Surgical Approaches.

Acute severe ulcerative colitis (ASUC) is a life-threatening medical emergency with considerable morbidity. Despite recent advances in medical IBD therapy, colectomy rates for ASUC remain high. A scoping review of published articles on ASUC was performed. We collected data, such as general information of the disease, diagnosis and initial assessment, and available medical and surgical treatments focusing on technical aspects of surgical approaches. The most relevant articles were considered in this scoping review. The management of ASUC is challenging; currently, personalized treatment for it is unavailable. Sequential medical therapy should be administrated, preferably in high-volume IBD centers with close patient monitoring and indication for surgery in those cases with persistent symptoms despite medical treatment, complications, and clinical worsening. A total colectomy with end ileostomy is typically performed in the acute setting. Managing rectal stump is challenging, and all individual and technical aspects should be considered. Conversely, when performing elective colectomy for ASUC, a staged surgical procedure is usually preferred, thus optimizing the patients' status preoperatively and minimizing postoperative complications. The minimally invasive approach should be selected whenever technically feasible. Robotic versus laparoscopic ileal pouch-anal anastomosis (IPAA) has shown similar outcomes in terms of safety and postoperative morbidity. The transanal approach to ileal pouch-anal anastomosis (Ta-IPAA) is a recent technique for creating an ileal pouch-anal anastomosis via a transanal route. Early experiences suggest comparable short- and medium-term functional results of the transanal technique to those of traditional approaches. However, there is a need for additional comparative outcomes data and a better understanding of the ideal training and implementation pathways for this procedure. This manuscript predominantly explores the surgical treatment of ASUC. Additionally, it provides an overview of currently available medical treatment options that the surgeon should reasonably consider in a multidisciplinary setting.

Changes in the clinical course and prognosis of ulcerative colitis in Chinese populations: a retrospective cohort study.

Data on the natural course of Chinese patients with ulcerative colitis (UC) was lacking. This study aimed to evaluate the natural history and prognosis of patients with UC in the past 15 years in China. This cohort study included patients with UC in a tertiary hospital in southern China from 2007 to 2021 (cohort I: 2007-2011, cohort II: 2012-2016, cohort III: 2017-2021). Patients' clinical characteristics and natural history were analyzed retrospectively. Of 1,139 included patients, 683 patients presented with proctitis or left-sided colitis at diagnosis and 38.5% of them (263/683) developed proximal disease extension. Fifty-eight percent of patients experienced relapse, chronic continuous and intermittent active course. Five patients (0.4%) developed colorectal tumors/dysplasia. The overall surgery rate was 8.6%, and the rates were 14.2%, 7.8%, and 8.0% in the 3 cohorts, respectively (P= 0.059). Average time from diagnosis to surgery decreased from cohorts I to III (144 months vs. 36 months, P< 0.001), so did the use of glucocorticoids (58.2% vs. 43.5%, P< 0.001) and immunosuppressants (14.1% vs. 13.4%, P= 0.016), and days of hospitalization (13 days vs. 9 days, P< 0.001). Biologics were used more frequently during the first year (0.8%, 2.1%, and 13.7% for cohorts I to III, respectively; P< 0.001). The rate of mucosal healing increased over time. In Chinese UC patients, one-third of patients experienced proximal disease extension. The rates of malignancy and mortality were low. More biologics were used, while use of immunosuppressants and glucocorticoids were reduced over time. Early biologics use seemed to promote mucosal healing, but the rate of colectomy has not dramatically decreased.

Defining management strategies for acute severe ulcerative colitis using predictive models: a simulation-modeling study.

Robust management algorithms are required to reduce the residual risk of colectomy in acute severe ulcerative colitis (ASUC) refractory to standard infliximab salvage therapy. The aim of this study was to evaluate the performance and benefits of alternative ASUC management strategies using simulated prediction models of varying accuracy. This was a simulation-based modeling study using a hypothetical cohort of 5,000 steroid-refractory ASUC patients receiving standard infliximab induction. Simulated predictive models were used to risk-stratify patients and escalate treatment in patients at high risk of failing standard infliximab induction. The main outcome of interest was colectomy by 3 months. The 3-month colectomy rate in the base scenario where all 5,000 patients received standard infliximab induction was 23%. The best-performing management strategy assigned high-risk patients to sequential Janus kinase inhibitor inhibition and mediumrisk patients to accelerated infliximab induction. Using a 90% area under the curve (AUC) prediction model and optimistic treatment efficacy assumptions, this strategy reduced the 3-month colectomy rate to 8% (65% residual risk reduction). Using an 80% AUC prediction model with only modest treatment efficacy assumptions, the 3-month colectomy rate was reduced to 15% (35% residual risk reduction). Overall management strategy efficacy was highly dependent on predictive model accuracy and underlying treatment efficacy assumptions. This is the first study to simulate predictive model-based management strategies in steroid-refractory ASUC and evaluate their effect on short-term colectomy rates. Future studies on predictive model development should incorporate simulation studies to better understand their expected benefit.

Effect of Tofacitinib on One-Year Colectomy Risk in Anti-TNF Refractory Ulcerative Colitis: A Prospective Multicenter Italian Study.

Tofacitinib is an oral Janus kinase inhibitor recently approved to induce and maintain remission in ulcerative colitis (UC). Considering the number of anti-TNF non-responders, this study aims to assess the effectiveness and safety of tofacitinib in a cohort of multi-failure patients with moderate-to-severe UC at 52weeks. From January 2021 to March 2023, we performed a prospective multicenter study observing adult patients with moderate-to-severe UC starting tofacitinib after an anti-TNF failure for a 52-week-long period. Effectiveness and safety were assessed in terms of colectomy rate, clinical remission and response, endoscopic remission, steroid-free clinical remission, and rate of adverse events. We included 58 patients with UC with an age of 42 ± 14.4years, 59% males, 96.6% left-sided or pancolitis, who were failure to a single (65.5%) or more than one anti-TNF (34.5%). Only 6 (10.3%) patients underwent colectomy. Colectomy was clinically associated with the necessity and the number of extra cycles of tofacitinib 10mg bid at W8 (p = 0.023) and W24 (p = 0.004), and with a higher partial Mayo score at W8 (p = 0.025). At W52, clinical remission, clinical response, and steroid-free clinical remission were 53.4%, 43.1%, and 48.3%, respectively. Of 22 performed colonoscopies at W52, 11 (50%) showed endoscopic remission. Adverse events occurred in 14 (24.1%) patients, but only 2 (3.4%) led to tofacitinib discontinuation. In a real-life setting of patients with anti-TNF refractory UC, tofacitinib has proved to be effective in preventing colectomy and inducing clinical and endoscopic remission at 52weeks with a good safety profile.

Early Initiation of Biologics and Disease Outcomes in Adults and Children With Inflammatory Bowel Diseases: Results From the Epidemiology Group of the Nationwide Israeli Inflammatory Bowel Disease Research Nucleus Cohort

In this nationwide study, we explored whether early initiation of biologics is associated with improved outcomes in children and adults with Crohn's disease (CD) and ulcerative colitis (UC). All patients diagnosed with CD or UC in Israel (2005-2020) were included in the Epidemiology Group of the Israeli Inflammatory Bowel Disease Research Nucleus cohort, encompassing 98% of the population. We compared disease duration at biologics initiation (ie, 0-3 months, >3-12 months, >1-2 years, and >2-3 years) using the cloning, censoring, and weighting by inverse probabilities method to emulate a target trial, adjusting for time-varying confounders and selection bias. Of the 34,375 included patients (of whom 5240 [15%] were children), 7452 of 19,264 (39%) with CD and 2235 of 15,111 (15%) with UC received biologics. In CD, by 10 years postdiagnosis, the probability of CD-related surgery decreased gradually but modestly with earlier initiation of biologics; a significant difference was noted between >2-3 years (31%) and 0-3 months (18%; P= .02; number needed to treat, 7.7), whereas there was no difference between the 0-3-month and >3-12-month periods. The 10-year probability of steroid dependency for the 0-3-month period (19%) differed both from the >2-3-year (31%; P < .001) and 1-2-year periods (37%; P < .001). In UC, no significant differences in colectomy or steroid dependency rates were observed between the treatment initiation periods. Similar trends were noted in the pediatric population. Very early initiation of biologics was not associated with some outcomes except for a modest risk reduction of surgery and steroid dependency for CD, which requires confirmation in future studies. In UC, early introduction of biologics was not associated with reduced risk of colectomy or steroid dependency.