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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.

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

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.

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.

Tofacitinib has emerged as a new option for ulcerative colitis. Its rapid absorption, metabolism, and clinical improvement make it an interesting option for rescue therapy in acute severe ulcerative colitis (ASUC), a situation with limited therapeutic options in patients with a long-term disease course and multiple drug failure. The management of ASUC in this setting becomes challenging, underlying the need for new drugs and data on their efficacy and safety. We describe 2 cases of acute episodes in which tofacitinib was used as a rescue therapy.

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.

Angelo Viscido,1 Claudio Papi,2 Giovanni Latella,1 Giuseppe Frieri11Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy; 2IBD Unit, S. Filippo Neri Hospital, Rome, ItalyAbstract: Ulcerative colitis (UC) still has no definitive cure since its etiology remains unclear. In recent years, considerable progress has been made with regard to our knowledge of the pathogenesis of UC. Advances in biotechnology have led to the development of biologic therapies which selectively target single key mediators or receptors involved in the pathogenesis of the disease – ie, tumor necrosis factor (TNF)-α, integrin, interleukins 12/23. Biologic therapies caused a revolution in the treatment of UC, providing specific options for patients refractory to conventional treatment. In recent years, antibodies anti-TNFα and anti-integrin have shown efficacy in improving the course and prognosis of ambulatory patients with moderate-to-severe UC. Nevertheless, whether biologics have brought so many benefits also for hospitalized patients with acute severe UC is still debated. Acute severe UC is a potentially life-threatening condition that affects up to 25% of patients during the course of their disease. It requires hospital admission due to the risk of complications and death, and it can necessitate urgent colectomy. Major adverse outcomes of acute severe UC are mortality and colectomy. The aim of this systematic review of the literature was to analyze the impact of biologics, in particular infliximab, on the course and prognosis of acute severe UC. Mortality and colectomy rates were considered as outcome measures.Keywords: ulcerative colitis, acute severe ulcerative colitis, mortality, colectomy, biologic therapy, infliximab