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Acute severe ulcerative colitis (ASUC) is a medical emergency that affects approximately 25% of patients with ulcerative colitis at some point in time in their lives. Outcomes of ASUC are highly variable. Approximately 30% of patients do not respond to corticosteroids and up to 50% of patients do not respond to rescue therapy (infliximab or cyclosporin) and require emergency colectomy. Data are emerging on infliximab dosing strategies, use of cyclosporin as a bridge to slower acting biologic agents and Janus kinase inhibition as primary and sequential therapy. In this review, we outline contemporary approaches to clinical management of ASUC in the setting of failure to respond to traditional rescue therapies. [ABSTRACT FROM AUTHOR]

Introduction: Acute severe ulcerative colitis (ASUC) is a life-treating presentation of ulcerative colitis (UC) that requires prompt initiation of treatment to avoid complication. Unfortunately, outcomes for ASUC are suboptimal, with as many as 20–30% of patients requiring colectomy. This can be challenging for patients and highlights the need to understand patient experiences and perspectives navigating ASUC. Methods: A qualitative descriptive study utilizing semi-structured interviews was conducted to understand perspectives and experiences of patients navigating ASUC. Adult patients hospitalized for ASUC between January 2017 and March 2024 were eligible. Interviews were conducted both retrospectively among patients with a recent hospitalization and prospectively among patients within 24 h of hospitalization for ASUC. Interviews were analyzed using a well-established hybrid inductive-deductive approach. Results: Thirty-four patients (44.2% response rate) hospitalized for ASUC were interviewed. Hybrid thematic analysis uncovered five major themes: (1) the pervasive impact of UC on QoL and mental health, (2) challenges associated with navigating uncertainty, (3) prioritizing colon preservation, (4) bridging the divide between outpatient expectations and inpatient realities, and (5) balancing rapid symptom improvement with steroid safety. Our findings advocate for transparent approach to care, emphasizing the need for effective communication, education, and better alignment with patient values and expectations. Conclusion: Five key themes were identified, each with significant implications for developing a more patient-centered approach to ASUC care. These themes captured meaningful insight into patient perceptions and experiences, identifying multiple areas for actionable interventions to improve care. [ABSTRACT FROM AUTHOR]

Introduction: Acute severe ulcerative colitis (ASUC) represents a life-threatening medical emergency. One-third of ASUC patients are steroid non-responders. Our study aimed to create a new ASUC algorithm to predict corticosteroid response in the early course of the disease. Materials and Methods: A cross-sectional study included 103 patients with ASUC (65 male, 38 female). We calculated the serum CRP to 25-hydroxy 25 OH vitamin D ratio at admission. Logistic regression determined patients' response to glucocorticoids, depending on the CRP/25 OH vitamin D ratio value. Results and Discussion: Significant differences were observed in the CRP/25 OH vitamin D ratio at admission between glucocorticoid responders and non-responders (p = 0.001). A negative correlation was found between glucocorticoid response and CRP/25 OH vitamin D levels (Spearman's rho = −0.338, p < 0.01). Logistic regression revealed a significant association (p = 0.003) with a model chi-square value of 11.131 (p = 0.001). ROC curve analysis showed an AUC of 0.696 (p = 0.001), indicating moderate discriminatory ability. To achieve 91% sensitivity, the CRP/25 OH vitamin D ratio must be less than 3.985 to predict a complete glucocorticoid response. Conclusions: The serum CRP to 25 OH vitamin D ratio on the first day of hospital admission can potentially determine the response to glucocorticoids in patients with ASUC and significantly affect the mortality of these patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. [ABSTRACT FROM AUTHOR]

Upadacitinib is an oral new selective JAK1 inhibitor that has been approved for treating adult patients with moderately to severely active ulcerative colitis. However, a growing number of studies are needed on the effectiveness of upadacitinib in the treatment of acute severe ulcerative colitis. This study was mainly aimed to describe the clinical and endoscopic effectiveness of upadacitinib 45 mg in Chinese acute severe ulcerative colitis patients following eight weeks of treatment. In this study, we examined all patients with acute severe ulcerative colitis from Xijing IBD Center, Xi'an, China, with acute severe ulcerative colitis. All patients were initially given oral upadacitinib 45 mg. Clinical indicators, C-reactive protein, and erythrocyte sedimentation rates were collected. Clinical response and clinical remission were assessed using modified Mayo. Endoscopic evaluation was performed carried out using the Mayo Endoscopic Score and Ulcerative colitis endoscopic index of severity score. A total of 14 patients who received upadacitinib were included in the study period. All patients exhibited a clinical response to 45 mg upadacitinib initially. All patients completed the 8-week induction. The clinical remission rate was 28.6% after eight weeks. Two patients revealed endoscopic remission at 14.3%. The pathology improved in 50.0% of patients. The 8-week surgical resection rate was 7.1%, with the 16-week surgical resection rate being 14.3%. Adverse events included herpes simplex virus infection and increased thrombin time. The results of our study support the short-term effectiveness and safety of upadacitinib in acute severe ulcerative colitis, providing new choices for patients' treatment. However, more extended investigation needs to be performed on the long-term effectiveness and safety. [ABSTRACT FROM AUTHOR]

This study assesses 2 different disease activity measures, the Modified Truelove Witts Severity Index and the partial Mayo score, in hospitalized patients with acute severe ulcerative colitis (UC) for prediction of postdischarge corticosteroid-free clinical remission and endoscopic improvement to help guide future considerations for disease activity assessment. In this post hoc analysis from the Tofacitinib for Hospitalized Acute Severe Ulcerative Colitis Management (TRIUMPH) trial, these results suggest resolution of the Mayo rectal bleeding subscore may have high prognostic utility and could be considered as a primary end point for hospitalized UC trials. The study underscores the need for further research on patient-reported outcomes and endoscopic indices in larger populations for inpatient UC trials. [ABSTRACT FROM AUTHOR]

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

INTRODUCTION: Intravenous corticosteroids are the mainstay of treatment of patients hospitalized with acute severe ulcerative colitis (ASUC). However, 30%-40% of the patients are refractory to corticosteroids. We investigated whether addition of tofacitinib to corticosteroids improved the treatment responsiveness in patients with ASUC. METHODS: This single-center, double-blind, placebo-controlled trial randomized adult patients with ASUC (defined by the Truelove Witts severity criteria) to receive either tofacitinib (10 mg thrice daily) or a matching placebo for 7 days while continuing intravenous corticosteroids (hydrocortisone 100mgevery 6 hours). The primary end point was response to treatment (decline in the Lichtiger index by >3 points and an absolute score <10 for 2 consecutive days without the need for rescue therapy) by day 7. The key secondary outcome was the cumulative probability of requiring initiation of infliximab or undergoing colectomy within 90 days following randomization. All analyses were performed in the intention-to-treat population. RESULTS: A total of 104 patients were randomly assigned to a treatment group (53 to tofacitinib and 51 to placebo). At day 7, response to treatment was achieved in 44/53 (83.01%) patients receiving tofacitinib vs 30/51 (58.82%) patients receiving placebo (odds ratio 3.42, 95% confidence interval 1.37-8.48, P 5 0.007). The need for rescue therapy by day 7 was lower in the tofacitinib arm (odds ratio 0.27, 95% confidence interval 0.09-0.78, P 5 0.01). The cumulative probability of need for rescue therapy at day 90 was 0.13 in patients who received tofacitinib vs 0.38 in patients receiving placebo (log-rank P 5 0.003). Most of the treatment-related adverse effects were mild. One patient, receiving tofacitinib, developed dural venous sinus thrombosis. DISCUSSION: In patients with ASUC, combination of tofacitinib and corticosteroids improved treatment responsiveness and decreased the need for rescue therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Acute severe ulcerative colitis (ASUC) is a potentially life-threatening complication of ulcerative colitis (UC) that can lead to significant morbidity and mortality, with a substantial number of patients needing colectomy. Infliximab (IFX) has been increasingly used as a rescue therapy for patients who have failed intravenous steroids and has been more frequently used as an induction and maintenance therapy in moderate-to-severe UC. Therefore, the number of patients admitted with ASUC previously exposed to IFX has been increasing, raising additional challenges in the medical management of these patients to avoid emergent colectomy. This narrative review intends to summarise the most recent evidence in the medical management of steroid-refractory ASUC patients previously exposed to IFX and to propose a treatment algorithm for approaching this difficult-to-treat group of patients.

Background and Aims: Approximately 1 in 4 patients with ulcerative colitis experiences a severe exacerbation of disease requiring hospitalization, termed acute severe ulcerative colitis (ASUC). These episodes pose a major burden on patients with ulcerative colitis and early prediction of their outcomes based on clinical data is crucial to optimize therapy. Methods: A systematic review was performed using Embase and Medline for articles between 2000 and 2023. Studies obtained from the databases were uploaded on Covidence for screening by 2 independent reviewers. Quality appraisal for each study was done using the Critical Appraisals Skills Program depending on study design. Results: A total of 48 eligible studies were included in the review. The key predictors of ASUC identified in this review included clinical, endoscopic, and radiographic biomarkers, which were summarized. The main outcomes assessed in the studies were intravenous corticosteroid failure, need for rescue therapy, and need for colectomy. Score-based predictions and some novel markers were also included in the results. Conclusion: Utilization of evidence-based predictors of outcome in ASUC could serve as a powerful tool in customizing therapeutic measures and a step forward toward personalized patient care. Despite promising candidates, there remains a significant opportunity to identify and test additional clinical and laboratory-based predictors, especially early in the hospitalization and as the clinical practice and medical therapies evolve.

Abstract Recent data, indicating that inflammatory bowel disease (IBD) may be a risk factor for future chronic kidney disease, highlight the need to study the safety and clinical effectiveness of advanced IBD therapies in patients with end stage renal disease (ESRD), defined as an eGFR

Introduction: Acute severe ulcerative colitis (ASUC) represents a life-threatening medical emergency. One-third of ASUC patients are steroid non-responders. Our study aimed to create a new ASUC algorithm to predict corticosteroid response in the early course of the disease. Materials and Methods: A cross-sectional study included 103 patients with ASUC (65 male, 38 female). We calculated the serum CRP to 25-hydroxy 25 OH vitamin D ratio at admission. Logistic regression determined patients’ response to glucocorticoids, depending on the CRP/25 OH vitamin D ratio value. Results and Discussion: Significant differences were observed in the CRP/25 OH vitamin D ratio at admission between glucocorticoid responders and non-responders (p = 0.001). A negative correlation was found between glucocorticoid response and CRP/25 OH vitamin D levels (Spearman’s rho = −0.338, p < 0.01). Logistic regression revealed a significant association (p = 0.003) with a model chi-square value of 11.131 (p = 0.001). ROC curve analysis showed an AUC of 0.696 (p = 0.001), indicating moderate discriminatory ability. To achieve 91% sensitivity, the CRP/25 OH vitamin D ratio must be less than 3.985 to predict a complete glucocorticoid response. Conclusions: The serum CRP to 25 OH vitamin D ratio on the first day of hospital admission can potentially determine the response to glucocorticoids in patients with ASUC and significantly affect the mortality of these patients.

Acute severe ulcerative colitis (ASUC) is one of life-threatening complications that occur in one-fifth of ulcerative colitis (UC) patients with significant morbidity and an estimated mortality rate up to 1%. There are no validated clinical scoring systems for ASUC. Intravenous corticosteroids remain the cornerstone for the management of ASUC patients However, one-third of patients are steroid refractory and require colectomy in the pre-biologic era or salvage therapy in the post-biologic era. The currently available predictors of non-response to steroids and salvages therapy are sub-optimal. Furthermore, there is a need for the development of clear outcome measures for ASUC patients. Although infliximab and cyclosporin are both effective as salvage therapy, they still carry a rate of treatment failure. Hence, there is an unmet need to explore alternative therapeutic options before colectomy particularly in prior infliximab-exposed patients. This may include the introduction of small molecules with rapid onset of action as a salvage or sequential therapy and the use of slow-onset other biological therapy after "bridging" with cyclosporine. In this article, we explore the current best evidence-based practice and detail the gaps in knowledge in the management of ASUC. [ABSTRACT FROM AUTHOR]

Background: This multicenter observational cohort study aimed to evaluate the utilization and short-term efficacy of advanced therapy (AT) in hospitalized patients with acute severe ulcerative colitis (ASUC). Methods: In total, 221 patients with ASUC were enrolled between August 2020 and July 2021. The primary endpoint was clinical remission (CR, defined as a patient-reported outcome score < 2 with no blood in the stool) rate on Day 7 and 14 in hospitalized patients who received corticosteroids (CS) and AT. Results: Among patients with ASUC, 120 and 101 patients received CS or any AT as first-line treatment, respectively. The CR rates on Day 7 and 14 were 22.5% and 35.0%, respectively, in hospitalized patients who received CS as first-line treatment. Most patients who used ATs had CS-dependent or frequent recurrences. Eight different ATs (apheresis, tacrolimus, infliximab, golimumab, tofacitinib, vedolizumab, ustekinumab, and cyclosporine) were used as first-line treatment in patients with ASUC, and the CR rates on Day 7 and 14 were 16.8% and 29.7%, respectively. Twenty-five patients received the second ATs after hospitalizations, and the CR rates on Day 7 and 14 were 0% and 12%, respectively. The CR rates on Day 14 were significantly higher in patients who changed to AT than in those whose dose of CS increased (34.0% vs 10.7%, p = 0.020) among patients who had already used CS before hospitalization. Conclusion: Most first-use ATs were effective for patients with ASUC, while second-use ATs might have had limited benefits in inducing CR. These findings may contribute to considerations for the management of hospitalized patients. [ABSTRACT FROM AUTHOR]

Background: In 2014, infliximab (IFX) was listed on the Australian Pharmaceutical Benefits Scheme for acute severe ulcerative colitis (ASUC) and is now the preferred option for medical salvage, superseding cyclosporin A (CsA). Optimal dosing schedules for IFX remain unknown. Aim: The authors aim to evaluate the effect of changing from predominantly CsA to almost exclusively IFX for the treatment of steroid‐refractory ASUC on colectomy rates. Methods: A retrospective review was performed of patients admitted with ASUC between 2012 and 2020. Patients were categorised into two groups according to year of presentation – either 'historical treatment' cohort (2012–2014), when CsA was primarily used, or 'contemporary treatment' cohort (2014–2020), when IFX was mostly prescribed, in either standard or intensive doses. Results: One hundred thirty‐nine patients were included; 37 in the historical treatment cohort and 102 in the contemporary treatment cohort. In the historical treatment cohort, 12 of 37 received salvage therapy and eight (67%) received CsA. In the contemporary treatment cohort, 49 of 102 patients received salvage therapy, 40 (82%) with IFX, of whom 22 (53%) received intensified doses. Colectomy rates were similar at 30 days, 6 months and 12 months between historical and contemporary treatment cohorts (14% vs 12% [P = 0.77], 19% vs 18% [P > 0.99],and 22% vs 18% [P = 0.63], respectively). Difference in 12‐month colectomy rates between standard versus intensive IFX did not meet statistical significance (three of 21 [14%] vs nine of 22 [41%]. respectively; P = 0.09). Conclusion: There was no difference in 30‐day, 6‐month or 12‐month colectomy rates between the historical treatment and contemporary treatment cohorts. The use of IFX, rather than CsA, even at intensified dosing, does not appear to reduce the colectomy rate observed in our patients. [ABSTRACT FROM AUTHOR]

Background and Aims Acute severe ulcerative colitis [ASUC] is a medical emergency treated with intravenous steroids followed by infliximab or cyclosporin in the case of steroid failure with emergent colectomy required in refractory or severe cases. Case series have reported on the effectiveness of tofacitinib for refractory disease, but data regarding the effectiveness of upadacitinib in this setting have not been previously reported. We describe the use of upadacitinib therapy for steroid-refractory ASUC in patients with prior loss of response to infliximab. Methods Six patients who received upadacitinib for steroid-refractory ASUC were identified at two Australian tertiary inflammatory bowel disease centres. Patients were followed for up to 16 weeks after discharge with clinical, biochemical and intestinal ultrasound [IUS] outcomes. Results All six patients demonstrated clinical response to upadacitinib induction during their inpatient admission. Four patients achieved corticosteroid-free clinical remission by week 8, including complete resolution of rectal bleeding and transmural healing assessed by IUS, and sustained clinical remission at week 16. One patient proceeded to colectomy at week 15 due to refractory disease. No adverse events directly attributable to upadacitinib were identified. Conclusions Upadacitinib may have a role as a safe and effective salvage therapy for steroid-refractory ASUC in patients who have previously failed to respond to infliximab therapy. Prospective studies are required to determine the safety and efficacy of upadacitinib use in this setting before routine use can be recommended. [ABSTRACT FROM AUTHOR]

Recent data, indicating that inflammatory bowel disease (IBD) may be a risk factor for future chronic kidney disease, highlight the need to study the safety and clinical effectiveness of advanced IBD therapies in patients with end stage renal disease (ESRD), defined as an eGFR <15 mL/min/1.73m2. Upadacitinib, a selective oral Janus kinase (JAK) 1 inhibitor, has demonstrated efficacy in the management of moderate to severe ulcerative colitis. There is also emerging data indicating that JAK inhibition may be clinically effective in the setting of steroid‐refractory acute severe ulcerative colitis (ASUC). There is, however, a lack of "real‐world" data documenting the use of JAK inhibitors in patients with ESRD. Here, we report the use of upadacitinib in a patient with ESRD for the management of steroid‐refractory ASUC, demonstrating, for the first time, the safe and clinically effective use of upadacitinib in this population. [ABSTRACT FROM AUTHOR]

Acute severe ulcerative colitis (ASUC) is strongly associated with poor prognosis. We aimed to establish and validate a model predicting ASUC occurrence within 1 year after ulcerative colitis(UC) diagnosis. A cohort of UC patients diagnosed between 2018 and 2020 at Northern Jiangsu People's Hospital, who were followed up for one year, was used to develop a risk prediction model. An independent cohort from January to December 2021, monitored until December 2022 at the at the First Affiliated Hospital of Nanjing Medical University, was used for external validation. A multivariable logistic regression analysis was conducted to investigate the adjusted association between six risk factors and ASUC. Subsequently, a simplified model was developed by eliminating a relatively insignificant risk factor to create an easy-to-use index. The prediction model incorporates five parameters: disease extent, endoscopic appearance, histopathology, baseline response medication, and relapse frequency. It generates a nomogram in the end. The discriminant ability (c-index) was separately calculated as 0.982 and 0.925 in the development and validation cohorts. The risk prediction model for developing ASUC within one year demonstrated excellent reliability and validity, which could be a straightforward and clinically valuable tool for predicting ASUC occurrence within 1 year. ChiCTR2300071794 [ABSTRACT FROM AUTHOR]

Approximately 20% of patients with ulcerative colitis (UC) develop acute severe UC (ASUC), for which intravenous systemic steroid therapy and possibly infliximab-based rescue therapy are generally imposed. However, there are no significant guideline recommendations on ASUC regarding vedolizumab as an alternative in this setting. A case report was presented where a patient with steroid-dependent UC developed ASUC induced by second-line chemotherapy. Treatment with intravenous methylprednisolone was imposed, but there was no reduction in bowel movements in the days following admission. Rescue therapy with infliximab was contraindicated because of the oncologic history. Surgical consultation, contraindicated colectomy, and administration of vedolizumab 300 mg were initiated. After infusion with vedolizumab, there was a significant reduction in bowel movements starting the day after infusion until normalisation of bowel movements within three days and the concomitant normalisation of inflammatory indices. The patient is currently in clinical remission, on therapy with vedolizumab 108 mg subcutaneously every two weeks, and is in oncologic follow-up for pulmonary neoplasm. This case highlights the novel potential of vedolizumab as a possible rescue therapy in ASUC, especially in special populations, where it may offer a better safety profile. Although cyclosporine and infliximab still represent the mainstays of salvage therapy for steroid-refractory ASUC, new therapeutic agents may also be effective, such as vedolizumab, ustekinumab, and anti-Janus kinase agents.

Abstract Background and Aim Acute severe ulcerative colitis (ASUC) remains a significant cause of morbidity and healthcare utilization. This study aimed to characterize the total healthcare costs of ASUC, explore factors associated with significant cost over the 12 months following an index admission, and document outcomes including corticosteroid exposure. Methods Patients admitted from January 2016 until January 2021 for ASUC to a tertiary inflammatory bowel disease (IBD) center in Australia were identified via retrospective chart review. Costs were calculated over a 12‐month period following index admission. Results Seventy‐two patients (30 [42%] female, median age 39 [IQR 27–54] years) were included. The median length of stay of index admission was 6 days (IQR 5–10 days). The median cost of index admission was 7829 AUD, which was driven by the initial length of stay (P

Despite rescue therapy, acute severe ulcerative colitis (ASUC) is associated with a high risk of colectomy, while treatment options remain limited. Tofacitinib, a rapidly acting Janus Kinase (JAK) inhibitor, is gaining ground as an effective alternative treatment option for the management of acute severe ulcerative colitis, which may prevent emergency colectomy. A systematic literature search of PubMed and Embase was undertaken for studies of adult patients with ASUC treated with tofacitinib. In total, two observational studies, seven case series and five case reports incorporating 134 patients who received tofacitinib in ASUC were identified with a follow-up period ranging from 30 days to 14 months. Overall, the pooled colectomy rate was 23.9% (95% CI 16.6–31.2). The pooled 90-day and 6-month colectomy free rate were 79.9% (95% CI 73.1–86.7) and 71.6% (95% CI 64–79.2) respectively. The most frequent adverse event was C. Difficile infection. Tofacitinib appears to be a promising option for the treatment of ASUC. Randomized clinical trials are required to further access the efficacy, safety and optimal dose of tofacitinib in cases of ASUC. [ABSTRACT FROM AUTHOR]

Increased C-reactive protein (CRP) is used to diagnose and predict response to treatment in acute severe ulcerative colitis (UC). To investigate the connection between CRP elevation and deep ulcers in UC. Patients with active UC were enrolled in a multicenter prospective cohort and a retrospective cohort of consecutive patients undergoing colectomy from 2012 to 2019. Forty-one (9 (22%) with deep ulcers) patients were included in the prospective cohort: 4/5 (80%) patients with CRP > 100 mg/L, 2/10 (20%) patients with CRP between 30 and 100 mg/L and 3/26 (12%) patients with CRP < 30 mg/L had deep ulcers (p = 0.006). In the retrospective cohort [46 patients (31 (67%) with deep ulcers)], 14/14 (100%) patients with CRP > 100 mg/L, 11/17 (65%) patients with CRP between 30 and 100 mg/l and 6/15 (40%) patients with CRP < 30 mg/L had deep ulcers (p = 0.001). Positive predictive value of CRP > 100 mg/l for presence of deep ulcers was 80% and 100% in both cohorts, respectively. CRP elevation is a robust surrogate marker for presence of deep ulcers in UC. Elevated CRP or presence of deep ulcers could influence the choice of medical therapy in acute severe UC. [ABSTRACT FROM AUTHOR]

Approximately 20% of patients with ulcerative colitis (UC) develop acute severe UC (ASUC), for which intravenous systemic steroid therapy and possibly infliximab-based rescue therapy are generally imposed. However, there are no significant guideline recommendations on ASUC regarding vedolizumab as an alternative in this setting. A case report was presented where a patient with steroid-dependent UC developed ASUC induced by second-line chemotherapy. Treatment with intravenous methylprednisolone was imposed, but there was no reduction in bowel movements in the days following admission. Rescue therapy with infliximab was contraindicated because of the oncologic history. Surgical consultation, contraindicated colectomy, and administration of vedolizumab 300 mg were initiated. After infusion with vedolizumab, there was a significant reduction in bowel movements starting the day after infusion until normalisation of bowel movements within three days and the concomitant normalisation of inflammatory indices. The patient is currently in clinical remission, on therapy with vedolizumab 108 mg subcutaneously every two weeks, and is in oncologic follow-up for pulmonary neoplasm. This case highlights the novel potential of vedolizumab as a possible rescue therapy in ASUC, especially in special populations, where it may offer a better safety profile. Although cyclosporine and infliximab still represent the mainstays of salvage therapy for steroid-refractory ASUC, new therapeutic agents may also be effective, such as vedolizumab, ustekinumab, and anti-Janus kinase agents. [ABSTRACT FROM AUTHOR]

Background Tofacitinib has emerged as a new potential treatment for acute severe ulcerative colitis [ASUC]. We conducted a systematic review to assess efficacy, safety and integration in ASUC algorithms. Methods Systematic searching was done in MEDLINE, EMBASE, Cochrane Library and Clinicaltrials.gov until August 17, 2022, including all studies reporting original observations on tofacitinib for ASUC, preferably defined according to Truelove and Witts criteria. The primary outcome was colectomy-free survival. Results Of 1072 publications identified, 21 studies were included of which three were ongoing clinical trials. The remaining comprised a pooled cohort originating from 15 case publications [ n  = 42], a GETAID cohort study [ n  = 55], a case-control study [ n  = 40 cases] and a paediatric cohort [ n  = 11]. Of these 148 reported cases, tofacitinib was used as second-line treatment after steroid failure in previous infliximab failures or third-line after sequential steroid and infliximab or cyclosporine failure, 69 [47%] were female, median age range was 17–34 years and disease duration was 0.7–10 years. Overall, 30-day colectomy-free survival was 85% [ n  = 123 of 145; n  = 3 without colectomy had follow-up <30 days], 90-day 86% [ n  = 113 of 132; n  = 16 follow-up <90 days] and 180-day 69% [ n  = 77 of 112; n  = 36 follow-up <180 days]. Tofacitinib persistence at follow-up was 68–91%, clinical remission 35–69% and endoscopic remission 55%. Adverse events occurred in 22 patients, predominantly being infectious complications other than herpes zoster [ n  = 13], and resulted in tofacitinib discontinuation in seven patients. Conclusion Tofacitinib appears promising for treatment of ASUC with high short-term colectomy-free survival among refractory patients who are otherwise deemed to require colectomy. However, large high-quality studies are needed. [ABSTRACT FROM AUTHOR]

Background and Aim: Acute severe ulcerative colitis (ASUC) remains a significant cause of morbidity and healthcare utilization. This study aimed to characterize the total healthcare costs of ASUC, explore factors associated with significant cost over the 12 months following an index admission, and document outcomes including corticosteroid exposure. Methods: Patients admitted from January 2016 until January 2021 for ASUC to a tertiary inflammatory bowel disease (IBD) center in Australia were identified via retrospective chart review. Costs were calculated over a 12‐month period following index admission. Results: Seventy‐two patients (30 [42%] female, median age 39 [IQR 27–54] years) were included. The median length of stay of index admission was 6 days (IQR 5–10 days). The median cost of index admission was 7829 AUD, which was driven by the initial length of stay (P < 0.01) and requirement for colectomy (P < 0.01). Median total healthcare cost over the first 12 months was 13 873 AUD (IQR 9684–19 936 AUD), again predominately driven by the length of stay (P < 0.01) and requirement for colectomy (P < 0.01). Median cumulative corticosteroid use over 12 months inclusive of index hospitalization was 1760 mg (IQR 1560–2350 mg). Requirement for inpatient medical salvage therapy with infliximab was associated with increased corticosteroid requirement (P = 0.01). Conclusion: Healthcare expense related to ASUC remains high, driven predominantly by the length of stay during initial hospitalization and need for colectomy. From a healthcare cost perspective, novel methods to reduce inpatient hospital stay as well as need for colectomy may help reduce the economic and steroid burden of ASUC. [ABSTRACT FROM AUTHOR]

Background One-third of patients with acute severe ulcerative colitis [ASUC] are steroid-refractory. We aimed to review the different options for the management of steroid-refractory ASUC, including not only the standard treatment [cyclosporine and infliximab], but also most recently developed agents [such as vedolizumab, ustekinumab, and tofacitinib]. Methods We performed a bibliographical search to identify studies focusing on the treatment of steroid-refractory ASUC. Results Cyclosporine and infliximab currently represent the mainstays of salvage therapy and they are generally considered comparable. However, long-term persistence is higher in infliximab therapy, and many clinicians prefer to use infliximab given its ease of use. However, cost of cyclosporine is lower. Sequential rescue therapy after cyclosporine or infliximab failure [with infliximab and cyclosporine, respectively] could be considered in referral centres for highly selected cases. Tofacitinib, due to its rapid effect, represents an attractive rescue option mainly in biologic-experienced patients. The good safety profile of vedolizumab and ustekinumab makes them ideal candidates for use as maintenance therapy in combination with cyclosporine as induction therapy, especially for patients previously exposed to anti-TNFs or thiopurines. Conclusions Although cyclosporine and infliximab still represent the mainstays of salvage therapy for steroid-refractory ASUC, new therapeutic agents may also play a role. Tofacitinib, due to its rapid effect, is an attractive therapeutic rescue option. Vedolizumab and ustekinumab, as maintenance therapy in combination with the fast-acting cyclosporine as induction therapy, may represent a promising bridging strategy, especially in patients with previous failure to thiopurines and/or anti-TNF agents. [ABSTRACT FROM AUTHOR]

Lately, emerging data suggest an association between the development of inflammatory bowel disease and anti-interleukin-17 therapy. Megacolon is a life-threatening complication of acute severe ulcerative colitis (ASUC), but its treatment has not yet been established in current practice guidelines. We report a rare case of known psoriasis treated by secukinumab in a patient who presented with ASUC and colonic dilatation. Neither steroids nor standard infliximab regimen was effective. Finally, rescue therapy with accelerated infliximab strategy resulted in excellent recovery. In certain cases of steroid-refractory ASUC complicated by megacolon, accelerated infliximab regimen can be an alternative to surgery.

Acute severe ulcerative colitis (ASUC) is a life-threatening medical emergency with considerable morbidity (30% to 40%). Patients with ASUC require hospitalization for prompt medical treatment, and colectomy is considered if medical therapy fails. Corticosteroids remain the primary initial therapy, although one-third of patients do not respond to treatment. Clinical data have indicated that cyclosporine, tacrolimus, and infliximab can be used to treat patients with ASUC who do not respond to intravenous corticosteroids. The effectiveness and safety of sequential therapy have recently been reported; however, the data are not convincing. Importantly, timely decision-making with rescue therapy or surgical treatment is critical to manage ASUC without compromising the health or safety of the patients. In addition, risk stratification and the use of predictive clinical parameters have improved the clinical outcome.of ASUC. Multidisciplinary teams that include inflammatory bowel disease experts, colorectal surgeons, and other medical staff contribute to the better management of patients with ASUC. In this review, we introduce current evidence and present a clinical approach to manage ASUC.

Inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) tend to increase in frequency and prevalence worldwide and lead to a significant reduction in quality of life with a complicated course. Intravenous administration of corticosteroids in acute severe ulcerative colitis is effective in 60–70 % of cases. Rescue therapy for patients with steroid‐refractory and steroid-dependence attacks is effective for reducing colectomy or colproctectomy and improves long-term treatment outcomes. Despite the proven efficacy of infliximab, limitations to the use of monoclonal antibodies are adverse reactions to the administration of genetically engineered biologic therapy (GEBT), both well-known and studied, and rare.The aim of the study. To analyze a case of an extremely rare and paradoxical incurable hyperergic reaction that occurred after using genetically engineered biological therapy with tumor necrosis factor alpha blockers in a patient suffering from ulcerative colitis.Materials and methods. We carried out the search in the PubMed, Embase, Scopus and Medline databases until November 1, 2022 using the following keywords: inflammatory bowel disease, ulcerative colitis (UC), anti-tumor necrosis factor α (antiTNFα), infliximab, fever, adverse events. In the scientific electronic library eLIBRARY, a search was made for Russian-language publications using similar queries in Russian. We analyzed the patient’s medical records from 03.06.2013 up to the present day; the patient signed an informed consent for the publication and discussion of the presented data.Conclusion. The widespread use of GEBT in the treatment of autoimmune and autoinflammatory diseases leads to the accumulation of both positive and negative experience of clinicians in real clinical practice. The officially described adverse events in the appointment of any drug suggest options for their prevention and treatment. Atypical manifestations or casuistic cases must be systematized for further fundamental pathophysiological studies.

Acute severe ulcerative colitis (ASUC) is an emergent medical condition and particularly challenging to treat efficaciously. Infliximab is one of the medical salvage treatment options after corticosteroid refractoriness, but the best induction strategy is not yet defined. With this case series, the authors intend to describe three corticosteroid-refractory ASUC cases with different intensified/accelerated infliximab induction approaches and review the literature on this topic.The first case describes an 18-year-old girl with ASUC at disease onset with rapid progression to toxic megacolon, complicated also with anemia, hypoalbuminemia, and coagulopathy. After corticosteroid failure, both accelerated and intensified (10 mg/kg) infliximab regimen was completed within 11 days, with solid clinical response and colon imaging normalization. Second, we present a 26-year-old male with left-sided ulcerative colitis known for 2 years, under mesalazine, who developed a moderate flare and was started on infliximab after partial and inconsistent response to corticosteroids. During the induction period, he presented this time an ASUC episode, which motivated an early and intensified third dose with good clinical response. Finally, we describe the case of a 78-year-old man with ulcerative proctitis for 12 years presenting ASUC with proximal disease extension as well. After unsatisfactory response to corticosteroids, infliximab was initiated on an accelerated induction regimen, completed in 13 days, with the standard dose, achieving clinical remission. Accelerated or intensified infliximab induction plans are becoming current clinical practice in corticosteroid-refractory ASUC. Current guidelines refer to the possibility of this type of strategies, not determining the optimal regimen due to lack of solid evidence. Literature is mainly based on retrospective studies, not randomized, with heterogeneous groups according to disease severity, and the effect on colectomy rates, mainly on the long term, is not clear. Additional well-supported studies are needed on this subject in order to seek a more widely uniform approach.

Therapeutic drug monitoring (TDM) is a useful strategy in ulcerative colitis (UC). Nearly a quarter of UC patients will experience acute severe UC (ASUC) in their lifetime, including 30% who will fail first-line corticosteroid therapy. Steroid-refractory ASUC patients require salvage therapy with infliximab, cyclosporine, or colectomy. Fewer data are available for the use of TDM of infliximab in ASUC. The pharmacokinetics of ASUC make TDM in this population more complex. High inflammatory burden is associated with increased infliximab clearance, which is associated with lower infliximab drug concentrations. Observational data support the association between increased serum infliximab concentrations, lower clearance, and favorable clinical and endoscopic outcomes, as well as decreased rates of colectomy. Data regarding the benefit of accelerated or intensified dosing strategies of infliximab—as well as target drug concentration thresholds—in ASUC patients remain more equivocal, though limited by their observational nature. Studies are underway to further evaluate optimal dosing and TDM targets in this population. This review examines the evidence for TDM in patients with ASUC, with a focus on infliximab. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of cytomegalovirus (CMV) colitis in the setting of severe ulcerative colitis (UC) remains a clinical challenge. This study aimed to determine the utility of serum CMV polymerase chain reaction (PCR) as a non-invasive test for the diagnosis of CMV superinfection in patients hospitalized with UC. Methods: This retrospective study included consecutive admitted patients with UC who had serum testing for CMV completed as part of standard hospital procedure and CMV colitis diagnosed by expert pathologists. Results: Two hundred and six patients with UC were included; 13 patients (6%) had histologically confirmed CMV colitis. Eleven of 13 patients with CMV colitis (84%) and 3 of 193 (1.5%) patients without CMV colitis had a positive serum PCR test (p < 0.0001). ROC analysis showed that a CMV PCR level of 259 IU/mL had a sensitivity and specificity of 77% and 99%, respectively, for diagnosis of CMV colitis with an AUC of 0.9 (p < 0.0001). Serum CMV PCR level significantly correlated to the number of inclusion bodies on biopsy specimens with data available (n = 8) (r = 0.8, p = 0.02). CMV positivity did not predict the need for salvage therapy, admission or 1-year colectomy rates. Conclusion: Serum CMV PCR has an excellent negative predictive value and demonstrates a strong correlation with CMV positivity on histology. This work supports a rationale for serum CMV PCR testing on admission to assess the risk of CMV colitis in patients with severe UC. [ABSTRACT FROM AUTHOR]

Background The standard therapy for acute severe ulcerative colitis (ASUC) is intravenous corticosteroids; however, 30% of ulcerative colitis (UC) patients do not recover with corticosteroids alone. Few studies have reported the efficacy and safety of tofacitinib for ASUC with steroid resistance. We report a case series of successful first-line treatment consisting of tofacitinib (20 mg/day) administered to ASUC patients with steroid resistance. Methods Patients diagnosed with ASUC at our institution between October 2018 and February 2020 were retrospectively evaluated. They were administered a high dose of tofacitinib (20 mg) after showing no response to steroid therapy in a dose of 1-1.5 mg/kg/day. Results Eight patients with ASUC, 4 (50%) men, median age 47.1 (range 19-65) years, were included. Four patients were newly diagnosed, and the median UC duration was 4 (range 0-20) years. Six of the 8 patients were able to avoid colectomy. One patient (patient 2) had no response; however, remission was achieved after switching from tofacitinib to infliximab. One patient (patient 6) with no response to tofacitinib underwent total colectomy. Only one patient (patient 4) experienced an adverse event, local herpes zoster, treated with acyclovir without tofacitinib discontinuation. Conclusions Clinical remission without serious adverse events can be achieved with high probability and colectomy can be avoided by first administering high-dose tofacitinib to steroid-resistant ASUC patients. Tofacitinib may be one of the first-line treatment options for steroid-resistant ASUC. [ABSTRACT FROM AUTHOR]

Lately, emerging data suggest an association between the development of inflammatory bowel disease and anti-interleukin-17 therapy. Megacolon is a life-threatening complication of acute severe ulcerative colitis (ASUC), but its treatment has not yet been established in current practice guidelines. We report a rare case of known psoriasis treated by secukinumab in a patient who presented with ASUC and colonic dilatation. Neither steroids nor standard infliximab regimen was effective. Finally, rescue therapy with accelerated infliximab strategy resulted in excellent recovery. In certain cases of steroid-refractory ASUC complicated by megacolon, accelerated infliximab regimen can be an alternative to surgery. [ABSTRACT FROM AUTHOR]

Acute severe ulcerative colitis is a rapidly progressive severe form of colitis that can occur in 20-30% patients with ulcerative colitis. Early recognition, hospitalization at centers with experience and expertise and multidisciplinary treatment is the cornerstone of appropriate management of this condition. After excluding infections and other differentials, patients should be started on parenteral corticosteroids to control inflammation. ASUC patients are at high risk for thromboembolic complications and hence DVT prophylaxis is ideally started as soon as possible in the emergency room and continued throughout hospitalization. Objective criteria should be applied to assess improvement and identify patients who are unlikely to improve without second line/rescue therapy as early as 72 hours on steroid therapy. Infliximab and cyclosporine are the most used options for second line therapy and should be administered under direction by gastroenterologists. Disease progression despite aggressive treatment or non-response to second line therapy, complications such as megacolon, perforation, hemorrhage can occur requiring colectomy as a salvage option in those patients. [ABSTRACT FROM AUTHOR]

Abstract Background Intravenous corticosteroid is the mainstay for managing acute severe ulcerative colitis, but one-third of patients do not respond to intravenous corticosteroid. Tacrolimus, a salvage therapy before colectomy, is usually orally administered, though its bioavailability is low compared intravenous administration. The efficacy of intravenous tacrolimus has not been widely studied. Aim To determine the efficacy and safety of intravenous tacrolimus for the treatment of acute severe ulcerative colitis. Methods Eighty-seven hospitalized acute severe ulcerative colitis patients were enrolled for a prospective cohort study between 2009 and 2017. Sixty-five patients received intravenous tacrolimus and 22 received oral tacrolimus. The primary outcome was the achievement of clinical remission within 2 weeks. Relapse and colectomy incidence and adverse events were assessed at 24 weeks. Results Response rates of both treatments exceeded 50% but were not significantly different. The remission rate was higher in intravenous tacrolimus compared with oral tacrolimus. At 24 weeks, oral and intravenous tacrolimus showed similar relapse-free survival rates; however, colectomy-free survival rates were higher in intravenous tacrolimus compared with oral tacrolimus. Conclusions Patients receiving intravenous tacrolimus achieved superior remission and colectomy-free survival rates compared with patients receiving oral tacrolimus. Safety was similar between the two treatments.

Background and Aims Our aim was to determine if transabdominal intestinal ultrasound changes after 48 ± 24 h of intravenous corticosteroids can predict treatment outcomes in hospitalised patients with severe ulcerative colitis. Methods We performed a blinded observational multicentre study. Ultrasound parameters were assessed before treatment initiation, after 48 ± 24 h, and 6 ± 1 days. Treatment response was determined within 7 days by two outcome measures: 1] partial Mayo score reduction; 2] no administration of rescue therapy. Results Out of 69 recruited patients, 56 were included in the final analysis, with 37 responders. The colon segment with the highest baseline bowel wall thickness was analysed, being the sigmoid in all patients. There was no difference in baseline bowel wall thickness between responders and non-responders in the partial Mayo score outcome. At 48 ± 24 h, a significant difference between responders and non-responders was identified in both absolute bowel wall thickness [median 3.1 mm vs 4.9 mm; p  <0.0001], absolute reduction [-1.9 mm vs -0.2 mm; p  <0.001], and relative reduction [-35.9% vs -4.1%; p  <0.0001]. A ≤20% reduction had a sensitivity of 84.2% (95% confidence interval [CI] 60.4, 96.6%) and a specificity of 78.4% [61.8, 90.2%] for determining non-response [area under the curve 0.85]. In the multivariable analysis, a >20% reduction had the highest odds ratio (22.6 [4.2, 201.2]; p  = 0.001) for determining response. Similar results were seen for the rescue therapy outcome. Conclusions Changes in bowel wall thickness, after 48 ± 24 h following intravenous corticosteroid treatment in hospitalised patients with severe ulcerative colitis, identify responders with high accuracy and might be used as an early marker to guide accelerated rescue therapy. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is part of the inflammatory bowels diseases, and moderate to severe UC patients can be treated with anti-tumour necrosis α monoclonal antibodies, including infliximab (IFX). Even though treatment of UC patients by IFX has been in place for over a decade, many gaps in modelling of IFX PK in this population remain. This is even more true for acute severe UC (ASUC) patients for which early prediction of IFX pharmacokinetic (PK) could highly improve treatment outcome. Thus, this review aims to compile and analyse published population PK models of IFX in UC and ASUC patients, and to assess the current knowledge on disease activity impact on IFX PK. For this, a semi-systematic literature search was conducted, from which 26 publications including a population PK model analysis of UC patients receiving IFX therapy were selected. Amongst those, only four developed a model specifically for UC patients, and only three populations included severe UC patients. Investigations of disease activity impact on PK were reported in only 4 of the 14 models selected. In addition, the lack of reported model codes and assessment of predictive performance make the use of published models in a clinical setting challenging. Thus, more comprehensive investigation of PK in UC and ASUC is needed as well as more adequate reports on developed models and their evaluation in order to apply them in a clinical setting. [ABSTRACT FROM AUTHOR]

Emergency subtotal colectomy is the standard treatment for acute severe ulcerative colitis (ASUC) unresponsive to medical treatment. No guidelines are available about surgical technique. The aim of the current survey was to identify the attitudes of Inflammatory Bowel Disease (IBD) surgeons concerning colectomy in patients with ASUC by means of a nationwide survey, with specific focus on intraoperative technical details. A survey was developed with focus on number of procedures performed, approach to vascular ligation, technique of bowel dissection, treatment of the omentum and of the rectal stump. Twenty Centres completed the survey. Seventy percent of responders started the colectomy laparoscopically. No significant differences were observed about vessels and mesocolic dissection as well as on the choice of the starting colon side and management of the omentum. Ileocolic vessels were ligated distally by 70% and at the origin by 30% and those who transect mesenteric vessels distally are significatively more likely to perform the dissection from lateral to medial and to cut the middle colic vessels distally and 100% of the ones linking left vessels at mesenteric axis transect middle colic vessels at the origin. No differences were observed in the treatment of rectal stump; however, all surgeons who performed a transrectal drainage (45%) left the rectal stump intraperitoneal (p < 0.05). No consensus exists about the technique of dissection, vascular ligation, treatment of the omentum and management of rectal stump. Further studies are needed to evaluate the impact of the different surgical techniques on patients' outcomes. [ABSTRACT FROM AUTHOR]

Background and Aims: 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., Methods: 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., Results: 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 < 21.5 kg/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 2.4 g/dL (OR = 10.61, P = .04) were significant predictors of inpatient colectomy after adjusting for sex, age, and duration of disease., Conclusions: 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., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Colectomy risk after acute severe ulcerative colitis (ASUC) has not been compared between Eastern and Western countries. We compared the 1-year colectomy risk after ASUC between Korea and the USA. Methods: Data on patients admitted for ASUC to five tertiary referral hospitals in Korea and Mount Sinai Hospital, New York, the USA, between January 2015 and January 2019 were reviewed retrospectively. For comparability between groups, a 1:1 propensity score matching (PSM) was performed. The primary outcome was colectomy, and secondary outcomes were mortality, readmission, and venous thromboembolism (VTE) within 1-year of the index admission for ASUC. The risk of each outcome was compared using Cox proportional hazards model in pre-matched cohort and Kaplan–Meier analysis with log-rank test in post-matched cohort. Results: 290 ASUC patients were included in the study (121 Korea, 169 the USA). After PSM, 56 patients were selected in each group with no significant differences in baseline variables. At 1 year after ASUC, colectomy was less common in Korea than in the USA [3 (5.4%) vs. 24 (42.9%), p < 0.001]. The cumulative colectomy risk was significantly higher in the USA than in Korea in pre-matched cohort [adjusted hazard ratio 7.89, 95% confidence interval 3.23 to 19.22] and in post-matched cohort (log-rank p < 0.001), while there was no difference in cumulative risk of mortality, readmission, and VTE. Conclusion: Colectomy risk within 1 year of ASUC is significantly higher in the USA than in Korea. We observed no differences in mortality, readmission, and VTE between the two groups. [ABSTRACT FROM AUTHOR]

Background: Optimal outcomes in acute severe ulcerative colitis (ASUC) are related to time-bound management based upon early prediction of response to intravenous (IV) steroids. In an earlier study, we described the All India Institute of Medical Sciences (AIIMS) index (baseline Ulcerative Colitis Endoscopic Index of Severity [UCEIS] ≥ 7 and day 3 fecal calprotectin [FCP] > 1000 μg/g) for predicting failure of IV steroids. The current study is designed to validate this index in a prospective cohort. Methods: IV steroid-naïve patients with ASUC, satisfying Truelove and Witts' criteria, hospitalized from August 2018 to July 2019 were included. Patients' assessment included baseline sigmoidoscopy, day 1 and 3 FCP, hemogram, biochemistry and day 3 C-reactive protein. All patients received IV steroids, and the primary outcome was steroid failure, defined as the need for colectomy or rescue therapy with cyclosporine (CYC)/infliximab (IFX) during admission. Results: Of the 47 patients, eight were excluded (four received steroids outside, two were directly taken for surgery/infliximab therapy, one had toxic megacolon, and one had infectious colitis), and 39 patients were included (mean age: 36.1 ± 12.6 years, male: 31%). Fifteen patients (38%) failed IV steroid and required rescue therapy (IFX: 9, CYC: 2, Colectomy: 3, IFX followed by colectomy: 1). On univariate analysis, UCEIS ≥ 7 at baseline (p = 0.006), day 1 FCP (p = 0.03), day 3 FCP > 1000 μg/g (p = 0.001), Oxford criteria (p = 0.04) and AIIMS index (p < 0.001) were significantly different between steroid responders and steroid failures. On multivariate analysis, day 3 FCP > 1000 μg/g (odds ratio (odds ratio (OR)= 6.4;(95% CI =2.2–196.1) and baseline UCEIS ≥ 7 (OR) = 10.1;(95% CI = 2.1–80.2) were independent predictors. The AIIMS index predicted steroid failure with a better specificity (100% vs. 83%, p = 0.04) and positive predictive value (100% vs. 64%, p = 0.03) than Oxford criteria. Conclusion: AIIMS index has been validated in 39 prospective ASUC patients as an effective early predictor of steroid failure (sensitivity = 53%, specificity = 100%). [ABSTRACT FROM AUTHOR]

Background: Steroid exposure has been associated with poorer outcomes following colectomy in acute severe ulcerative colitis (ASUC). Aim: To examine the effect of prolonged oral corticosteroid therapy immediately prior to admission on the likelihood of requiring rescue therapy along with predictors of intravenous corticosteroid failure on Day 1 of admission. Methods: A retrospective case note and electronic record review was conducted at a tertiary inflammatory bowel disease referral centre of admissions for ASUC meeting Truelove and Witts criteria from 2013 to 2019.The data was analysed for the effect of pre‐admission steroid exposure on need for rescue therapy and for predictors of intravenous corticosteroid failure. Results: Ninety‐two admissions were identified for ASUC meeting Truelove and Witts criteria. Over 1 week of steroid therapy prior to admission was associated with need for rescue therapy and trended to significance for colectomy at admission and at 12 months. A generalised linear model was constructed with multivariate regression significant for over 1 week of steroid therapy prior to admission, endoscopic Mayo score and albumin. The area under the receiver operator curve for this model was 0.86. Conclusion: Prolonged steroid use prior to ASUC admission is a significant predictor of need for rescue therapy. A generalised linear model incorporating steroid prior to admission, endoscopic Mayo score and albumin was highly accurate at predicting failure of corticosteroid. Consideration should be given for commencement of rescue therapy prior to Day 3, especially in those with prolonged steroid prior to admission. [ABSTRACT FROM AUTHOR]

Background The early prediction of intravenous corticosteroid (IVCS) resistance in acute severe ulcerative colitis (ASUC) patients remains an unresolved challenge. This study aims to construct and validate a model that accurately predicts IVCS resistance. Methods A retrospective cohort was established, with consecutive inclusion of patients who met the diagnosis criteria of ASUC and received IVCS during index hospitalization in Peking Union Medical College Hospital between March 2012 and January 2020. The primary outcome was IVCS resistance. Classification models, including logistic regression and machine learning-based models, were constructed. External validation was conducted in an independent cohort from Shengjing Hospital of China Medical University. Results A total of 129 patients were included in the derivation cohort. During index hospitalization, 102 (79.1%) patients responded to IVCS and 27 (20.9%) failed; 18 (14.0%) patients underwent colectomy in 3 months; 6 received cyclosporin as rescue therapy, and 2 eventually escalated to colectomy; 5 succeeded with infliximab as rescue therapy. The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and C-reactive protein (CRP) level at Day 3 are independent predictors of IVCS resistance. The areas under the receiver-operating characteristic curves (AUROCs) of the logistic regression, decision tree, random forest, and extreme-gradient boosting models were 0.873 (95% confidence interval [CI], 0.704–1.000), 0.648 (95% CI, 0.463–0.833), 0.650 (95% CI, 0.441–0.859), and 0.604 (95% CI, 0.416–0.792), respectively. The logistic regression model achieved the highest AUROC value of 0.703 (95% CI, 0.473–0.934) in the external validation. Conclusions In patients with ASUC, UCEIS and CRP levels at Day 3 of IVCS treatment appeared to allow the prompt prediction of likely IVCS resistance. We found no evidence of better performance of machine learning-based models in IVCS resistance prediction in ASUC. A nomogram based on the logistic regression model might aid in the management of ASUC patients. [ABSTRACT FROM AUTHOR]

Background: Intravenous corticosteroid is the mainstay for managing acute severe ulcerative colitis, but one-third of patients do not respond to intravenous corticosteroid. Tacrolimus, a salvage therapy before colectomy, is usually orally administered, though its bioavailability is low compared intravenous administration. The efficacy of intravenous tacrolimus has not been widely studied.Aim: To determine the efficacy and safety of intravenous tacrolimus for the treatment of acute severe ulcerative colitis.Methods: Eighty-seven hospitalized acute severe ulcerative colitis patients were enrolled for a prospective cohort study between 2009 and 2017. Sixty-five patients received intravenous tacrolimus and 22 received oral tacrolimus. The primary outcome was the achievement of clinical remission within 2 weeks. Relapse and colectomy incidence and adverse events were assessed at 24 weeks.Results: Response rates of both treatments exceeded 50% but were not significantly different. The remission rate was higher in intravenous tacrolimus compared with oral tacrolimus. At 24 weeks, oral and intravenous tacrolimus showed similar relapse-free survival rates; however, colectomy-free survival rates were higher in intravenous tacrolimus compared with oral tacrolimus.Conclusions: Patients receiving intravenous tacrolimus achieved superior remission and colectomy-free survival rates compared with patients receiving oral tacrolimus. Safety was similar between the two treatments. [ABSTRACT FROM AUTHOR]

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Acute severe ulcerative colitis (ASUC) is a medical emergency for which colectomy is required in patients who do not respond to rescue therapy. While previous studies have predominantly focused on predicting outcome to first-line corticosteroid therapy, there is a need to understand the factors associated with response to rescue therapies in order to improve clinical outcomes. We reviewed the evidence regarding factors associated with response to rescue therapy in adults with ASUC and identified future directions for research., Methods: A systematic search of the literature was conducted, and 2 reviewers independently assessed studies for inclusion., Results: Of 3509 records screened, 101 completed studies were eligible for inclusion. We identified 42 clinical, hematological, biochemical, endoscopic, or pharmacological factors associated with response to rescue therapy. Older age (≥50 years), thiopurine experience, and cytomegalovirus or Clostridioides difficile infection were associated with a higher risk of nonresponse to rescue therapy. Biochemical factors associated with poorer response included an elevated C-reactive protein (CRP) ≥30mg/L on admission, hypoalbuminemia and an elevated ratio of CRP to albumin. Severe endoscopic findings, including a Mayo endoscopic score of 3 or Ulcerative Colitis Endoscopic Index of Severity ≥5, portended poorer outcomes. The role of fecal calprotectin and therapeutic value of measuring infliximab drug levels in ASUC remain to be defined., Conclusions: Response to rescue therapy can be predicted by several specific factors, which would aid clinical decision-making. Existing and emerging factors should be integrated within predictive and prognostic models to help improve clinical outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Aims: 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., Methods: Six randomized controlled trials and 15 cohort studies including 2,004 patients were analyzed. Rescue drugs included tofacitinib, infliximab with a 5 or 10 mg/kg induction dose at 0, 2, and 6 weeks (IFX and IFX10, respectively), IFX with an accelerated regimen of three 5 mg/kg induction doses timed according to clinical need (accelerated IFX), tacrolimus, cyclosporine (CyA), ustekinumab, and adalimumab. Treatments were compared with a placebo., Results: 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., Conclusion: 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., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)