Steroid-Refractory Acute Severe Ulcerative Colitis in Infliximab-Experienced Patients.

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.

A colite ulcerosa aguda grave (CUAG) é uma complicação potencialmente fatal da colite ulcerosa (CU), que pode levar a significativa morbilidade e mortalidade, com um número substancial de doentes a necessitar de colectomia. O uso de infliximab (IFX) como terapêutica de resgate em doentes sem resposta a corticoterapia endovenosa tem vindo a aumentar, bem como a sua utilização como terapêutica de indução e manutenção em doentes com CU moderada-grave. Assim, o número de doentes hospitalizados com CUAG que já estiveram previamente expostos ao IFX tem vindo a aumentar, levantando novos desafios na abordagem médica destes doentes, de forma a evitar a colectomia emergente. Esta revisão narrativa tem como objetivo sumarizar a evidência mais recente na abordagem médica da CUAG refratária aos corticoides em doentes previamente expostos ao IFX e propor um algoritmo terapêutico para abordar este grupo desafiante de doentes.

Prognostic Value of CRP/25 OH Vitamin D Ratio for Glucocorticoid Efficacy in Acute Severe Ulcerative Colitis Patients.

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.

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

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.

In this prospective study, BMI lower than 21.5 kg/m, simple clinical colitis activity index greater than 8, and albumin lower than 2.4 g/dL at admission predicted the need for colectomy at the index hospitalization.

Effectiveness and safety of upadacitinib in acute severe ulcerative colitis patients from single Chinese IBD Center: a monocentric study.

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.

Understanding the Perspectives and Experiences of Patients with Acute Severe Ulcerative Colitis in the Hospital: A Qualitative Analysis.

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.

Systematic Review: Outcome Prediction in Acute Severe Ulcerative Colitis.

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.

Upadacitinib for Acute Severe Ulcerative Colitis: A Systematic Review.

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

This systematic review evaluates the efficacy and safety of upadacitinib in treating acute severe ulcerative colitis (ASUC). Results indicate that upadacitinib is a promising option for ASUC patients, with a low colectomy rate and high rates of steroid-free clinical remission.

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

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.

Comparison of accelerated and standard infliximab induction regimens in acute severe ulcerative colitis using propensity score analysis: a retrospective multicenter study in China.

Background: The optimal regimen of infliximab salvage in acute severe ulcerative colitis (ASUC) patients remains controversial. This study aimed to compare accelerated and standard infliximab induction in Chinese ASUC patients, and to explore risk factors and concrete accelerated regimens for them. Methods: Data were retrospectively collected from steroid-refractory ASUC patients receiving infliximab as rescue therapy at seven tertiary centers across China. Outcomes including colectomy and clinical remission (Mayo score ≤ 2 and every subscore ≤ 1 at Day 14) rates were compared between patients receiving accelerated and standard infliximab induction using propensity score adjustment for potential confounders. The dose-response relationship was explored by plotting restricted cubic splines. Logistic regression and Cox proportional hazards regression analyses were performed to determine risk factors for adverse outcomes. A systematic review and meta-analysis was also performed. Results: A total of 76 patients were analysed: 29 received standard and 47 received accelerated induction. The accelerated group had a higher 90-day colectomy rate (17.8% vs 0%, P = 0.019) and lower clinical remission rate (27.7% vs 65.5%, P = 0.001). After adjusting for propensity score and institution, there was no significant difference in colectomy or clinical remission rates (both P > 0.05). Dose-effect curves showed decreased colectomy hazard with higher cumulative infliximab dosage within 5 days, with no improvement observed for increasing cumulative infliximab dosage within 28 days. Multivariate logistic regression analyses revealed C-reactive protein of >10 mg/L at infliximab initiation (odds ratio = 5.00, 95% confidence interval: 1.27-24.34) as an independent risk factor for no clinical remission. Meta-analysis also revealed no significant difference in colectomy rates at 3 months (P = 0.54). Conclusions: After adjusting for confounders, there were no significant differences in colectomy or clinical remission rates between accelerated and standard infliximab induction among ASUC patients. Early administration of an intensified dosage within 5 days may be beneficial. Elevated C-reactive protein at infliximab initiation indicated need for intensive treatment.

Early intestinal ultrasound in severe ulcerative colitis identifies patients at increased risk of 1-year treatment failure and colectomy.

BACKGROUND AND AIMS: Reliable and easily accessible objective markers of disease activity to predict long-term treatment outcomes in severe ulcerative colitis (UC) are missing. We aimed to investigate if intestinal ultrasound (IUS) might predict long-term outcomes in hospitalized patients with severe UC treated with intravenous corticosteroids. METHODS: Hospitalized patients with severe UC and IUS inflammation (bowel wall thickness (BWT)>3.0mm) starting IV corticosteroids were recruited at three university hospitals in Denmark. IUS was performed before treatment, 48±24 hours (h), 6±1 days, and 3 months after treatment initiation. Time until colectomy or need for new interventions was registered together with Mayo score at 3 months and partial Mayo score (pMayo) at 12-months. Follow-up time was 12 months. RESULTS: Fifty-six patients were included in the final analysis. Forty-five (80%) patients needed intervention, including 9 colectomies, during the 12-month follow-up. After 48±24h: No patient with a BWT<3mm needed a colectomy, p=0.04. BWT≥4mm showed an increased risk of colectomy (odds ratio 9.5 (95%CI 1.5-186), p=0.03), while a BWT≥3mm showed an increased risk of intervention (3.6 (1.1-12.5), p=0.03). A BWT≥4mm resulted in a significantly shorter time until both colectomy, p=0.03, and treatment intensification (mean days 75 (95%CI24-127) vs. 176 (119-233), p=0.005. However, neither IUS parameters nor pMayo score, CRP, hemoglobin, or p-albumin could predict remission at 3- and 12-months. CONCLUSION: BWT assessed at 48h post intravenous corticosteroid initiation in patients hospitalized with severe UC may identify patients with an increased risk of short- and long-term colectomy and predict a more aggressive short-term disease course.

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

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

What to do when traditional rescue therapies fail in acute severe ulcerative colitis.

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.

Hyperbaric Oxygen Enabled a Transition to Oral Steroids in an Acute Severe Ulcerative Colitis Flare.

Background: Ulcerative colitis (UC) is characterized in part by a dysregulated response to tissue hypoxia. While intravenous (IV) steroids are the mainstay of treatment for acute severe UC (ASUC), up to one-third of patients are refractory to steroids alone and require rescue therapy. Case Description: A 71-year-old female with extensive UC on infliximab presented with abdominal pain and more than 10 bloody bowel movements per day. Her infliximab concentration was undetectable with a positive antibody level. Flexible sigmoidoscopy on hospital day (HD)1 showed Mayo 3 colitis; biopsies for CMV were negative. She was started on hydrocortisone IV with improvement in her CRP from 56 to 40 mg/L. She also received 1 dose of vedolizumab. Hyperbaric treatments were offered but declined. By HD5, she was clinically improved, with a CRP of 9 mg/L. She was transitioned from IV to oral steroids. After starting oral steroids her symptoms relapsed, her CRP increased from 9 to 48 mg/L, and IV steroids were reinitiated on HD6. Hyperbaric medicine was reconsulted and she completed 5 hyperbaric oxygen (HBO2) treatments (HD 7-11) with prompt reduction in CRP, stool frequency, and bleeding. After 3 HBO2 treatments, she transitioned successfully from IV to oral steroids on HD9. Conclusions: This case demonstrates the potential of HBO2 therapy to help UC patients transition successfully from IV to oral steroids who were previously refractory to de-escalation. HBO2 therapy may be considered as an adjunctive treatment for patients with ASUC to potentiate the effects of standard therapies and avoid progression to colectomy.

Modern practical management of acute severe colitis.

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.

Exclusive Enteral Nutrition Mediates Beneficial Gut Microbiome Enrichment in Acute Severe Colitis.

BACKGROUND: Exclusive enteral nutrition (EEN) supplementation of the standard of care (SOC) augments steroid responsiveness in patients with acute severe ulcerative colitis (ASUC). EEN is known to alter gut microbial composition. The present study investigates EEN-driven gut microbial alterations in patients with ASUC and examines their correlations with clinical parameters. METHODS: Stool samples from patients with ASUC (n = 44) who received either EEN-supplemented SOC (EEN group; n = 20) or SOC alone (SOC group; n = 24) for 7 days were collected at baseline (day 0) and postintervention (day 7). Microbiome analysis was carried out using 16S ribosomal RNA gene sequencing followed by data processing using QIIME2 and R packages. RESULTS: Seven-day EEN-conjugated corticosteroid therapy in patients with ASUC enhanced the abundances of beneficial bacterial genera Faecalibacterium and Veillonella and reduced the abundance of Sphingomonas (generalized linear model fitted with Lasso regularization with robustness of 100%), while no such improvements in gut microbiota were observed in the SOC group. The EEN-associated taxa correlated with the patient's clinical parameters (serum albumin and C-reactive protein levels). Unlike the SOC group, which retained its preintervention core microbiota, EEN contributed Faecalibacterium prausnitzii, a beneficial gut bacterial taxon, to the gut microbial core. EEN responders showed enhancement of Ligilactobacillus and Veillonella and reduction in Prevotella and Granulicatella. Analysis of baseline gut microbiota showed relative enhancement of certain microbial genera being associated with corticosteroid response and baseline clinical parameters and that this signature could conceivably be used as a predictive tool. CONCLUSIONS: Augmentation of clinical response by EEN-conjugated corticosteroid therapy is accompanied by beneficial gut microbial changes in patients with ASUC.

Exclusive enteral nutrition­supplemented corticosteroid therapy in acute severe ulcerative colitis (ASUC) is accompanied by the enrichment of beneficial gut microbial genera, which correlate negatively with the disease activity scores and objective inflammatory markers in ASUC. The baseline gut microbiota in ASUC associates with and may predict corticosteroid response.

Development and validation of a risk model to predict the progression of ulcerative colitis patients to acute severe disease within one year.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: ChiCTR2300071794.

Real-world efficacy and safety of advanced therapies in hospitalized patients with ulcerative colitis.

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.

Infliximab Induction Strategies in Corticosteroid-Refractory Acute Severe Ulcerative Colitis: A Case Series and Literature Review.

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.

A agudização grave de colite ulcerosa é uma emergência médica, particularmente difícil de tratar de forma eficaz. O infliximab é uma das opções de tratamento médico de resgate após refractariedade aos corticosteróides, porém a melhor estratégia de indução ainda não está definida. Com este relato de série de casos, os autores pretendem descrever três casos de agudização grave de colite ulcerosa refratária a corticosteróides com diferentes abordagens de indução intensificada/acelerada de infliximab e rever a literatura sobre este tópico. O primeiro caso descreve uma jovem de 18 anos com agudização grave de colite ulcerosa, à apresentação da doença, com rápida progressão para megacólon tóxico, complicada também com anemia, hipoalbuminemia e coagulopatia. Após ausência de resposta a corticosteróides, foi iniciado regime acelerado e intensificado (10 mg/kg) de infliximab, concluído em 11 dias, com resposta clínica e normalização das alterações imagiológicas do cólon. Em segundo lugar, apresentamos um homem de 26 anos com colite ulcerosa esquerda conhecida há 2 anos, sob messalazina, que apresentou uma agudização moderada da doença e iniciou infliximab após resposta parcial e inconsistente aos corticosteróides. Durante o período de indução, apresentou desta vez um episódio de agudização grave, o que motivou uma terceira dose precoce e intensificada com boa resposta clínica. Por fim, descrevemos o caso de um homem de 78 anos com proctite ulcerosa há 12 anos apresentando agudização grave de colite ulcerosa, também com extensão proximal da doença. Após resposta insatisfatória a corticosteróides, foi iniciado infliximab em regime de indução acelerada, completado em 13 dias, com a dose padrão, obtendo remissão clínica. Os esquemas de indução de infliximab acelerados ou intensificados têm vindo a tornar-se prática clínica habitual nos casos de agudização grave de colite ulcerosa refratária a corticosteróides. As diretrizes atuais referem a possibilidade deste tipo de estratégias, não indicando qual o regime ideal por falta de evidência sólida. A literatura baseia-se principalmente em estudos retrospetivos, não randomizados, com heterogeneidade de grupos de estudo de acordo com a gravidade da doença e o efeito nas taxas de colectomia, sobretudo a longo prazo, não é claro. Estudos mais fundamentados são necessários sobre esta matéria de modo a que seja possível uma abordagem amplamente mais uniforme.

Tofacitinib in Steroid-Refractory Acute Severe Ulcerative Colitis: A Retrospective Analysis.

INTRODUCTION: Steroid-refractory acute severe ulcerative colitis (ASUC) patients are at the highest risk of colectomy. Among the available options, cyclosporine and infliximab have similar efficacy but infliximab is a costly drug and cyclosporine has multiple side effects like kidney injury, neurotoxicity, and dyselectrolytemia. Surgical management is often associated with higher morbidity. Newer oral small molecules like Janus kinase inhibitors are the ideal molecules to bridge the gap. Tofacitinib has already been extensively evaluated in patients with moderate to severe UC; however, data on ASUC treated by tofacitinib are limited. METHODS: We retrospectively analyzed the data of patients with ASUC who were admitted to our hospital's luminal gastroenterology unit between January 2021 and July 2023. Patients with ASUC who were managed with tofacitinib were included in the study. RESULTS: Eight patients with ASUC were identified who did not respond to intravenous hydrocortisone and were treated with tofacitinib. The mean age was 39 ± 15 years and 87.5% were female. The median duration of illness was 24 months (interquartile range (IQR): 12-120 months). Seven of eight patients (87.5%) responded to oral tofacitinib 10 mg twice a day by the fifth day of treatment. The median follow-up period was six months (IQR: 1-12 months). One patient required colectomy and one patient had varicella zoster reactivation requiring treatment discontinuation. CONCLUSION: Tofacitinib is an attractive alternative to the currently available salvage therapy for steroid-refractory ASUC; however, long-term efficacy and risk remain to be explored.

In Acute Severe Ulcerative Colitis Patients Who Receive Rescue Therapy, Prior Maintenance Therapy and Day 3 C-Reactive Protein After Rescue Therapy Are Associated With 12-Month Colectomy Risk.

In steroid-refractory patients with acute severe ulcerative colitis, the number of advanced therapies prior to admission and day 3 C-reactive protein post­rescue therapy is associated with a higher risk of colectomy within 12 months.