Approximately one in every four patients with ulcerative colitis will develop acute severe ulcerative colitis (ASUC). Historically, this was managed with intravenous steroids and surgery when steroids failed. The use of rescue therapy.

This review summarizes the latest research in the management of hospitalized patients with ASUC. Covering the historical data and success of rescue therapy with cyclosporine and then with infliximab changed outcomes and reduced the risk of colectomy during the hospitalization and at 1 year. More recently, more biologics and small molecules have been approved and more patients present to the hospital with ASUC already failing anti-tumor necrosis factor antagonists. More recent studies have shown some efficacy of rescue therapy with other classes of biologics (e.g. interleukins and anti-integrins). The more recently approved small molecules (i.e. tofacitinib and Upadacitinib) have shown a rapid onset in therapeutic efficacy in as little as 1 day with sustained response at 1 year in reducing the risk of colectomy following ASUC.

In the expert opinion, we discuss the challenges in the treatment of patients with ASUC. We summarize the data of current biologics and new small molecules and their emerging roles in the management of ASUC.

One-third of patients presenting with acute severe ulcerative colitis (ASUC) are steroid-refractory and require either colectomy or rescue therapy. Timely identification of risk factors predictive of steroid non-response in ASUC patients is crucial for initiating early rescue therapy.

To identify factors predicting steroid failure or colectomy in ASUC.

Records of ASUC admissions over a six-year period in a tertiary inflammatory bowel disease center were included. Clinical variables, laboratory markers, and endoscopic scores at admission were obtained. The primary outcome was non-response to intravenous (IV) steroids. Univariate and multivariate regression analyses were performed to identify factors associated with steroid non-response. Day-one and day-three composite indices were calculated. Their predictive value was assessed against the outcomes of steroid failure and requiring colectomy.

One hundred and three ASUC patients were included, of which 51 were steroid non-responders. Among non-responders, 48 received rescue therapy, and 6 underwent colectomy at index admission (3 after rescue therapy and 3 without). Day-one albumin (OR 0.906, P = 0.043) and being on oral steroids at entry (OR 3.009, P = 0.014) predicted non-response to steroids in both univariate and multivariate analyses. Admission hemoglobin level predicted steroid non-response only in univariate (OR 0.982, P = 0.047). Although an old score, Travis criteria predicted both steroid non-response (OR 8.4, P = 0.001) and requiring colectomy (OR 22.19, P = 0.006).

Lower albumin levels and being on oral steroids at admission for ASUC can predict IV steroid failure, and we suggest the possibility of early initiation of advanced therapy in this subgroup.

Acute severe ulcerative colitis (ASUC) is a life-threatening medical emergency affecting over 20% of patients with ulcerative colitis (UC). Up to 40% of patients are refractory to intravenous corticosteroids (IVCS) and require rescue medical therapy or immediate colectomy. The potent Janus kinase (JAK) inhibitors, upadacitinib and tofacitinib, have proven efficacy in a randomised control trial setting for moderate-to-severe UC, but not ASUC. We describe a case series of sequential rescue therapy with JAK inhibitors following the failure of dose-intensified infliximab in corticosteroid-refractory ASUC. Six adult (>16 years old) patients received sequential rescue therapy with a JAK inhibitor (upadacitinib n = 5, tofacitinib n = 1) following failure of IVCS and dose-intensified infliximab at the Royal Brisbane and Women's Hospital (QLD, Australia) between October 2023 and April 2024. All patients met the Truelove and Witts criteria for ASUC on admission. Data were captured during admission and at 90-days post-discharge. Co-primary outcomes were 90-day colectomy-free survival and inpatient clinical response (<4 non-bloody stools per day) 72 h after JAK-inhibitor initiation. Secondary outcomes included 90-day clinical (PRO-2 score < 1) and biochemical (faecal calprotectin (FCP) < 150 µg/g and C-reactive protein (CRP) < 5 mg/L) corticosteroid-free remission and adverse events. Median CRP on admission was 100 mg/L (interquartile range (IQR) 58-105), median FCP 3400 µg/g (IQR 910-4950) and median Mayo Endoscopic Score 3. Four out of six patients had a clinical response within 72 h of sequential JAK-inhibitor rescue therapy. Two patients underwent emergent inpatient colectomy for refractory disease - one of whom developed post-operative sepsis. Among the four JAK-responders at 90 days, all achieved corticosteroid-free clinical remission and three achieved biochemical remission. No other adverse events were recorded. There is a promising role for JAK inhibitors as sequential rescue therapy following the failure of dose-intensified infliximab in select patients with corticosteroid-refractory ASUC.

Pregnancy-onset inflammatory bowel disease (POIBD) is a rare diagnosis that has been associated with diagnostic delay and increased risk of hospitalization compared with inflammatory bowel disease diagnosed outside of pregnancy. There is a paucity of data on the clinical presentation and risk factors associated with maternal and fetal outcomes of POIBD. We present a 29-year-old patient who presented with acute severe ulcerative colitis at 24 weeks gestational age whose course was complicated by delayed diagnosis and therapy, colonic perforation, colectomy, prolonged hospitalization, and neonatal prematurity. The case illustrates the high index for suspicion required for making this diagnosis and the prevention of maternal and neonatal morbidity, together with a growing need to advocate for timely investigations and in-patient management in unwell pregnant patients.

We present an interesting case of severe ulcerative colitis flare, of challenging management because of a cytomegalovirus co-infection, in which upadacitinib achieved clinical and biochemical remission after poor responses to ganciclovir and tofacitinib.

Ulcerative colitis is a chronic inflammatory condition of the colon driven by aberrant immune activation. Although advanced medical therapies form the cornerstone of ulcerative colitis management, unmet needs include failure to induce and sustain remission in a substantial proportion of patients and in managing acute severe ulcerative colitis. We review new treatment strategies that might improve patient outcomes in the management of moderate-to-severe ulcerative colitis.

A literature search was conducted using the PubMed database, including studies published from inception to October 2024, selected for their relevance. Recognizing current limitations, this article reviews strategies to improve treatment outcomes in ulcerative colitis using advanced therapies. These approaches include early treatment initiation, dose optimization, positioning newer agents as first-line therapies, combination therapy, targeting novel therapeutic endpoints, and the management of acute severe ulcerative colitis.

The strategies discussed may contribute to establishing new standards of care aimed at achieving long-term remission and enhancing patient outcomes. Personalized therapy, which tailors treatment based on individual disease characteristics and risk factors, is anticipated to become a critical aspect of delivering more effective care in the future.

It is unknown which maintenance therapy is the most effective option for patients admitted for an acute severe ulcerative colitis (ASUC) episode responding to intravenous steroids.

We conducted a multicentre, parallel-group, open-label randomised controlled trial among 23 French centres in thiopurine and biologics-naïve adults admitted for ASUC responding to intravenous steroids. Eligible patients were randomly assigned to receive infliximab (IFX) and azathioprine (AZA) with a 7-day steroid tapering scheme (IFX+AZA arm) or AZA and conventional standardised steroid tapering regimen (AZA arm). The primary composite endpoint was treatment failure at week 52, defined as the absence of steroid-free clinical remission, the absence of endoscopic response, the use of a prohibited treatment for relapse, severe adverse event leading to treatment interruption, colectomy or death. Multiple imputation for missing data was performed.

Among the 64 patients randomised (Lichtiger score 13.5±2.0; median age of 34.5 (P25-P75 26.3-50.3) years, median C reactive protein of 29.0 (12.8-96.8) mg/L at baseline): 32 were assigned to the IFX+AZA arm and 32 to the AZA arm. In the ITT population, treatment failure at week 52 was observed in 22/27 (81.5%) in the AZA arm and 16/30 (53.3%) in the IFX+AZA arm (risk ratio 3.85, 95% CI (1.15 to 12.88), p=0.03). 29 adverse events were severe, including 13 disease exacerbations, 6 severe infections without any difference between both arms.

Combination therapy with IFX+AZA was more effective at 1 year than AZA alone to avoid treatment failure in patients with ASUC responding to intravenous steroids.

NCT02425852.

Acute severe ulcerative colitis (ASUC) is a critical manifestation of ulcerative colitis (UC), often necessitating colectomy when medical management fails. Despite advancements in therapeutic interventions such as corticosteroids, biologics, and JAK inhibitors, a significant proportion of patients require surgery, with colectomy rates ranging from 10% to 15%.

This paper reviews the factors influencing the timing and necessity of colectomy in ASUC management, emphasizing the importance of multidisciplinary decision-making involving gastroenterologists and surgeons.

Key surgical indications include failure of medical therapy, toxic megacolon, perforation, uncontrolled bleeding, and systemic deterioration. Delays in surgery can result in higher morbidity and mortality rates, making timely intervention essential. This review highlights surgical techniques, including total colectomy and end ileostomy, and discusses potential complications, urging a balanced approach to optimize patient outcomes.

The role of various histologic scores in predicting outcomes in acute severe ulcerative colitis (ASUC) is unexplored.

Consecutive patients of ASUC undergoing sigmoidoscopy and histological assessment by two independent pathologists for Simplified Geboes score (SGS), Robarts Histopathology Index (RHI) and Nancy histological index (NHI)] were included. Primary outcome was the role of histology in predicting need for second-line therapy or colectomy.

Of 82 patients with ASUC (mean age: 36 years, males 47.5 %), non-response to steroids was observed in 27 (32.9 %) of cases. Sixteen patients required second-line drug therapy and 8 required colectomy. There was no significant association between the need for second-line therapy or colectomy and the baseline histological scores [NHI (p = 0.61), SGS (p = 0.116) and RHI (p = 0.109)]. All three scores performed poorly to predict the need for second-line treatment or colectomy within 28 days. There was no significant association between histological scores and steroid response (NHI (p = 0.796), SGS (p = 0.57) and RHI (p = 0.941)]. All three scores had a strong positive correlation observed between each other but not with endoscopic Mayo score.

The three histologic scores (SGS, RHI and NHI) performed poorly in prediction of need for second-line treatment or colectomy in ASUC. Future studies should study the impact of histologic assessment on long term outcomes in ASUC.

Interventional clinical trials in acute severe ulcerative colitis (ASUC) are characterized by substantial heterogeneity due to a lack of consensus in several key areas of trial design-this impedes clinical research efforts to identify novel therapies. The objective of this initiative was to achieve the first consensus and provide clear position statements on ASUC trial design.

A modified Delphi consensus approach was employed with a panel of 20 clinicians with international representation and expertise in ASUC trial design and delivery. Agreement was defined as at least 75% of participants voting as "agree" with each statement.

In total, 30 statements achieved consensus and were approved. Statements centred on proposing suitable eligibility criteria (disease extent, disease severity, prior therapy exposure), optimizing trial design (randomization, stratification, corticosteroid handling, timing of assessments), and recommending primary and secondary endpoints alongside defining key efficacy outcomes (clinical and endoscopic response and remission, treatment failure, quality of life).

The expansion of drugs to treat moderate-severe ulcerative colitis over the past decade, particularly the rapidly acting Janus kinase inhibitors, is promising and has reignited the interest in identifying suitable therapeutic candidates for ASUC. Clinical trials in this high-risk population are challenging to conduct and this consensus provides a framework for future trials to advance drug development.

Acute severe ulcerative colitis (ASUC) poses challenges to patient management owing to its high surgical rate. This study aimed to identify predictors of colectomy in patients with ASUC.

This is a systematic review and meta-analysis.

PubMed and Web of Science were searched up to April 2024.

Studies on the predictors of colectomy in adult patients with ASUC were eligible.

Two reviewers independently extracted the data using a prespecified data collection sheet. A qualitative synthesis was performed in tabular form. Random-effect meta-analyses were conducted using OR and 95% CI.

Forty-two studies were included in the systematic review. The reported variables can be categorised into biomarkers, auxiliary examination findings, demographic and clinical characteristics, and drug factors. Through meta-analysis, albumin (OR 0.39 (95% CI 0.26 to 0.59) per 1 g/dL increment, I2=0.0%), high C reactive protein level (2.63 (1.53 to 4.52), I2=29.6%), high erythrocyte sedimentation rate level (2.92 (1.39 to 6.14), I2=0.0%), low haemoglobin level (2.08 (1.07 to 4.07), I2=56.4%), fulfilling the Oxford criteria (4.42 (2.85 to 6.84), I2=0.0%), extensive colitis (1.85 (1.24 to 2.78), I2=47.5%), previous steroids (1.75 (1.23 to 2.50), I2=17.7%) or azathioprine (2.25 (1.28 to 3.96), I2=0.0%) use, and sarcopenia (1.90 (1.04 to 3.45), I2=0.0%) were identified as valuable predictors for colectomy within 1 year. The ulcerative colitis endoscopic index of severity (OR 2.41 (95% CI 1.72 to 3.39), I2=1.5%) was the only predictor found to predict colectomy over 1 year.

Identification of these predictors may facilitate risk stratification of patients with ASUC, drive personalised treatment and reduce the need for colectomy.

Overall, 30-40% patients with acute severe ulcerative colitis [ASUC] fail intravenous [IV] steroids, requiring medical rescue therapy/colectomy. Low baseline albumin predicts steroid non-response, and exclusive enteral nutrition [EEN] has been shown to improve steroid response and albumin levels. Albumin infusion, due to its anti-inflammatory and antioxidant properties, might further improve steroid response in ASUC, which was evaluated in the present study.

In this open-label, randomised, controlled trial, patients with ASUC were randomised in 1:1 ratio to either albumin + standard of care [SOC] + EEN [Albumin arm] or SOC + EEN [SOC arm], over January 2021-February 2023. Both arms received 5 days of EEN with 400 mg IV hydrocortisone/day. Patients in the Albumin arm were administered 5 days of 20% weight/volume [w/v] intravenous albumin [100 ml]. Primary outcome was first, steroid failure [need for rescue medical therapy or colectomy] and second, proportion of patients with adverse events.

In all, 61 patients [albumin: 30, SOC: 31][mean age 31.6 ± 0.4 years, male 57.4%], were included. Baseline characteristics were comparable. There was no difference in steroid failure between Albumin and SOC arms (10/30 [33.33%] vs 13/31[41.94%], p = 0.49). No adverse events were reported with albumin infusions. Colectomy rate [10% vs 9.68%, p = 1], response to salvage medical therapy [88.89% vs 76.92%, p = 0.62] and median [interquartile range] duration of hospitalisation [10.5 [7-16] vs 10 [7-20], p = 0.43] were also comparable. The long-term composite outcome of colectomy and re-admission rates was numerically higher in the Albumin than the SOC arm [37.04% vs 17.86%, p > 0.05], although this did not reach statistical significance.

There was no benefit of intravenous albumin infusion as an adjunct to IV steroids and EEN in patients with ASUC.

Severe colitis is a well-defined condition encompassing several etiologies but is most often caused by severe ulcerative colitis or Clostridioides difficile infection. Severe colitis can evolve into toxic colitis, or toxic megacolon when associated with bowel dilation and systemic manifestations, resulting in a life-threatening scenario where multidisciplinary management is often required. Medical management continues to play an important role in the initial treatment of toxic megacolon. However, timely surgical intervention can be lifesaving.

The optimal dosing strategy for infliximab in steroid-refractory acute severe ulcerative colitis (ASUC) is unknown. We compared intensified and standard dose infliximab rescue strategies and explored maintenance therapies following infliximab induction in ASUC.

In this open-label, multicentre, randomised controlled trial, patients aged 18 years or older from 13 Australian tertiary hospitals with intravenous steroid-refractory ASUC were randomly assigned (1:2) to receive a first dose of 10 mg/kg infliximab or 5 mg/kg infliximab (randomisation 1). Block randomisation was used and stratified by history of thiopurine exposure and study site, with allocation concealment maintained via computer-generated randomisation. Patients in the 10 mg/kg group (intensified induction strategy [IIS]) received a second dose at day 7 or earlier at the time of non-response; all patients in the 5 mg/kg group were re-randomised between day 3 and day 7 (1:1; randomisation 2) to a standard induction strategy (SIS) or accelerated induction strategy (AIS), resulting in three induction groups. Patients in the SIS group received 5 mg/kg infliximab at weeks 0, 2, and 6, with an extra 5 mg/kg dose between day 3 and day 7 if no response. Patients in the AIS group received 5 mg/kg infliximab at weeks 0, 1, and 3, with the week 1 dose increased to 10 mg/kg and given between day 3 and day 7 if no response. The primary outcome was clinical response by day 7 (reduction in Lichtiger score to <10 with a decrease of ≥3 points from baseline, improvement in rectal bleeding, and decreased stool frequency to ≤4 per day). Secondary endpoints assessed outcomes to day 7 and exploratory outcomes compared induction regimens until month 3. From month 3, maintenance therapy was selected based on treatment experience, with use of thiopurine monotherapy, combination infliximab and thiopurine, or infliximab monotherapy, with follow-up as a cohort study up to month 12. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02770040, and is completed.

Between July 20, 2016, and Sept 24, 2021, 138 patients were randomly assigned (63 [46%] female and 75 [54%] male); 46 received a first dose of 10 mg/kg infliximab and 92 received 5 mg/kg infliximab. After randomisation 1, we observed no significant difference in the proportion of patients who had a clinical response by day 7 between the 10 mg/kg and 5 mg/kg groups (30 [65%] of 46 vs 56 [61%] of 92, p=0·62; risk ratio adjusted for thiopurine treatment history, 1·06 [95% CI 0·94-1·20], p=0·32). We found no significant differences in secondary endpoints including time to clinical response or change in Lichtiger score from baseline to day 7. Two patients who received 10 mg/kg infliximab underwent colectomy in the first 7 days compared with no patients in the 5 mg/kg group (p=0·21). Three serious adverse events occurred in three patients in both the 10 mg/kg group and 5 mg/kg group. After randomisation 2, the proportions of patients with clinical response at day 14 (34 [74%] of 46 in the IIS group, 35 [73%] of 48 in the AIS group, and 30 [68%] of 44 in the SIS group, p=0·81), clinical remission at month 3 (23 [50%], 25 [52%], 21 [48%], p=0·92), steroid-free remission at month 3 (19 [41%], 20 [42%], 18 [41%], p=1·0), endoscopic remission at month 3 (21 [46%], 22 [46%], 21 [48%], p=0·98), and colectomy at month 3 (three [7%] of 45, nine [19%] of 47, five [12%] of 43, p=0·20) were not significantly different between groups. Between day 8 and month 3, the proportion of patients with at least one infectious adverse event possibly related to infliximab was two (4%) of 46 in the IIS group, eight (17%) of 48 in the AIS group, and eight (18%) of 44 in the SIS group (p=0·082). No deaths occurred in the study.

Infliximab is a safe and effective rescue therapy in ASUC. In steroid-refractory ASUC, a first dose of 10 mg/kg infliximab was not superior to 5 mg/kg infliximab in achieving clinical response by day 7. Intensified, accelerated, and standard induction regimens did not result in a significant difference in clinical response by day 14 or in remission or colectomy rates by month 3.

Australian National Health and Medical Research Council, Gastroenterology Society of Australia, Gandel Philanthropy, Australian Postgraduate Award, Janssen-Cilag.

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.

Toxic megacolon is a severe complication of ulcerative colitis characterized by extreme dilation of the colon, often leading to life-threatening outcomes. It typically presents with symptoms such as abdominal distension, severe pain, fever, and signs of systemic toxicity. We present a case of perforated toxic megacolon in a middle-aged woman with a new diagnosis of ulcerative colitis that was refractory to corticosteroids and biologic therapy. Early recognition and treatment are crucial to reduce morbidity and mortality associated with this potentially fatal condition.

In recent years, tofacitinib has been used in patients with acute severe ulcerative colitis (ASUC) as a rescue therapy with encouraging success rates. We present details of four patients with steroid-refractory ASUC treated with tofacitinib. All the patients were biologics-naive. Tofacitinib was initiated in a dose of 10 mg three times daily in three patients and 10 mg twice daily in the remaining patient. Three of the four patients improved and were discharged in clinical remission. These patients continue to be in colectomy-free and steroid-free remission on follow-up. The remaining patient did not respond to tofacitinib and required a colectomy. No adverse event related to tofacitinib use was noted in any of these four patients.

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.

Acute severe ulcerative colitis (ASUC) is a potentially life-threatening medical emergency that occurs in up to 25% of patients with ulcerative colitis. Although intravenous corticosteroids remain the cornerstone of therapy, 30-40% of patients will not respond and need timely consideration of rescue therapy with (currently) either infliximab or ciclosporin or indeed colectomy, underscoring the importance of multidisciplinary care to ensure favourable outcomes for patients. We discuss the current evidence and present an approach to the management of ASUC for general and specialist clinicians caring for patients with ASUC.

The information in this review is derived from data published in peer- reviewed academic journals and registered clinical trials.

Management of acute severe colitis requires a multidisciplinary approach with early initiation with steroids and timely escalation of treatment to either medical rescue therapy or surgery.

Balancing the risks of delayed surgery vs. optimizing medical therapy, including accelerated dosing schedules for biologics, remains ambiguous.

The position on newer molecules like Janus Kinase inhibitors, such as tofacitinib, is a growing area with early real-world data showing promise for steroid refractory ASUC.

Developing predictive biomarkers and clinical risk scores for personalized rescue therapy selection is an evolving area of research.

Inflammatory bowel disease (IBD) is rapidly emerging in the Asia Pacific region. However, there are many challenges in the diagnosis and management of this condition. The Asian Pacific Association of Gastroenterology (APAGE) Working Group on IBD conducted a round table meeting to identify 10 common mistakes in the management of IBD in Asia. To summarize, many physicians still over rely on a definitive histological diagnosis before starting treatment and do not fully establish disease extent such as perianal and proximal gastrointestinal involvement in Crohn's disease (CD) or extent of involvement in ulcerative colitis (UC). It is also essential to actively look for evidence of extra-intestinal manifestations, which may influence choice of therapy. In terms of conventional therapy, underuse of topical 5 aminosalicylates (5-ASAs) in UC and inappropriate dosing of corticosteroids are also important considerations. Acute severe UC remains a life-threatening condition and delay in starting rescue therapy after inadequate response to intravenous steroids is still common. Anti-tumor necrosis factors should be considered first line in all cases of complex perianal fistulizing CD. Most patients with IBD are on potent immunosuppressive therapy and should be screened for latent infections and offered vaccinations according to guidelines. Under-recognition and management of significant complications such as anemia, osteoporosis, malnutrition, and thromboembolism should also be addressed. Colonoscopy is still not properly performed for dysplasia/cancer surveillance and for evaluating post-op recurrence of CD. Another common misstep is inappropriate withdrawal of medications during pregnancy leading to increased complications for the mother and the newborn.

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.

A systematic search of the literature was conducted, and 2 reviewers independently assessed studies for inclusion.

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.

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.

Acute Severe Ulcerative Colitis (ASUC) is a severe form of ulcerative colitis relapse which requires hospitalization and intensive medical intervention to avoid colectomy. The timely recognition of patients at risk of corticosteroid failure and the early initiation of medical rescue therapy are paramount in the management of ASUC. The choice of medical rescue therapy is influenced by multiple factors, especially patient's prior treatment history. This decision should involve the patient and ideally a multidisciplinary team of healthcare professionals, including gastroenterologists, radiologists, surgeons and enterostomal therapists. Although several predictive models have been developed to predict corticosteroid failure in ASUC, there is no single validated tool that is universally utilized. At present, infliximab and cyclosporine are the only agents systematically evaluated and recommended for medical rescue therapy, with recent reports of off-label utilization of tofacitinib and upadacitinib in small case series. The available evidence regarding the efficacy and safety of these oral small molecules for ASUC is insufficient to provide definitive recommendations. Early decision-making to assess the response to medical rescue therapy is essential, and the decision to pursue surgery in the case of treatment failure should not be delayed.

Tofacitinib is indicated in patients with moderate to severe ulcerative colitis (UC); however, given its rapid onset of action, it may constitute an alternative in patients with hospitalized severe acute UC. There are few data on this indication in the literature. The aim of this study was to describe the efficacy and safety of tofacitinib in the management of patients with hospitalized UC, as well as its clinical characteristics and other treatment patterns.

Descriptive observational study of adults and children with CUAG treated with tofacitinib between June 2019 and December 2022 in Colombia. Sociodemographic and clinical variables were collected, therapeutic response was evaluated in different periods of time and descriptive analysis of quantitative and qualitative variables was performed.

Six patients (five adults and one pediatric), mean age 33.2 (SD: 8.5) years, with CUAG. Symptom remission was obtained in 100% of patients at day 7 after tofacitinib initiation. In three patients information was obtained beyond 6 months, with 100% clinical, biochemical, and endoscopic remission and without requiring colectomy. In the case of the pediatric patient, symptom remission was achieved one week after starting tofacitinib, remaining in clinical, biochemical and endoscopic remission beyond 6 months. No serious adverse events were reported in any of the cases.

Tofacitinib represents a rescue therapeutic alternative in CUAG, with rapid clinical response, adequate tolerance and less need for colectomy, being sustained for periods beyond 6 months.

Treatment of ulcerative colitis (UC) has been revolutionized by the arrival of biotherapies and technical progress in interventional endoscopy and surgery. (Sub)total emergency colectomy is required in the event of complicated severe acute colitis: colectasis, perforation, hemorrhage, organ failure. Corticosteroid therapy is the reference treatment for uncomplicated severe acute colitis, while infliximab and ciclosporin are 2nd-line treatments. At each step, before and after each line of treatment failure, surgery should be considered as an option. In cases refractory to medical treatment, the choice between surgery and change in medication must weigh the chronic symptoms associated with the disease against the risks of postoperative complications and functional sequelae inherent to surgery. Detection of dysplastic lesions necessitates chromoendoscopic imaging with multiple biopsies and anatomopathological verification. Endoscopic treatment of these lesions remains reserved for selected patients. These different indications call for multidisciplinary medical-surgical discussion. Total coloproctectomy with ileo-anal anastomosis (TCP-IAA) is the standard surgery, and it holds out hope for healing. Modalities depend on patient characteristics, previous emergency colectomy, and presence of dysplasia. It may be carried out in one, in two modified, or in three phases. The main complications are anastomotic fistula, short-term pouch-related fistula, ileo-anal pouch syndrome, pouchitis and long-term digestive and sexual disorders. For selected cases, an alternative can consist in total colectomy with ileo-rectal anastomosis or permanent terminal ileostomy. The objective of this update is to clarify the indications, modalities, and results of surgical treatment of ulcerative colitis in accordance with the most recent data in the literature.

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.

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.

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.

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.

Augmentation of clinical response by EEN-conjugated corticosteroid therapy is accompanied by beneficial gut microbial changes in patients with ASUC.

Hospitalization for ulcerative colitis (UC) is potentially life-threatening. Severe disease in the Japanese criteria which modifies the Truelove-Witts' criteria might encompass more fulminant cases than the definition for acute severe UC. However, few studies have investigated the predictive factors for clinical remission (CR) after medical treatments for severe hospitalized patients by Japanese criteria.

Medical treatment selection, CR rates, and factors contributing to CR on day 14 were assessed in severe patients by Japanese criteria. We also investigated whether the reduction rate in patient-reported outcome 2 (PRO2) on day 3 could predict short-term prognosis.

Eighty-five severe hospitalized patients were selected. Corticosteroids, tacrolimus, and infliximab were mainly selected as first-line treatments (76/85; 89.4%). The CR rates on day 14 were 26.8%, 21.4%, and 33.3% in patients receiving corticosteroids, tacrolimus, and infliximab, respectively. Extensive disease (odds ratio [OR] 0.022; 95% confidence interval [CI] 0.002-0.198), higher PRO2 (OR 0.306; 95% CI 0.144-0.821), and higher reduction rate in PRO2 on day 3 (OR 1.047; 95% CI 1.019-1.075) were independent factors predicting CR on day 14. If the cutoff value for the reduction rate in PRO2 on day 3 was 18.3%, sensitivity was 0.714 and specificity was 0.731 to predict CR on day 14. A higher reduction rate in PRO2 on day 3 (OR 0.922; 95% CI 0.853-0.995) was a negative factor to predict surgery within 28 days.

Tacrolimus and infliximab in addition to corticosteroids were used as first-line treatment in severe hospitalized patients. PRO2 on day 3 is a useful marker for switching to second-line therapy or colectomy.

Acute severe ulcerative colitis (ASUC) is a distinctive ulcerative colitis flare presentation characterised by the presence of systemic inflammation as well as bloody diarrhoea, and occurs at least once in 25% of patients with ulcerative colitis during their disease course. Each episode carries a risk of complications, need for colectomy, and mortality. Little is known about ASUC pathogenesis, although impaired host-microbiota crosstalk involving pathobionts is suspected. In this Review, we discuss unanswered questions and results from the latest research on the medical-first-line, second-line, and potential third-line therapies-and surgical management of ASUC. We detail promising options for management, such as the use of enteral nutrition in combination with intravenous steroids, the ability to predict early failure of first-line or second-line therapies, and the emerging role of JAK inhibitors. An optimal framework to personalise therapy on the basis of multiomics tools is yet to be developed.

In 2020 we reported the ACE Index in acute colitis which used biochemical and endoscopic parameters to predict steroid non-response on admission in patients with acute ulcerative colitis [UC]. We aimed to validate the ACE Index in an independent cohort.

The validation cohort comprised patients screened as eligible for inclusion in the CONSTRUCT study, a prospective, randomized, placebo-controlled trial which compared the effectiveness of treatment with infliximab vs ciclosporin in patients admitted with acute UC. The CONSTRUCT cohort database was reviewed at The Edinburgh IBD Unit and the same biochemical and endoscopic variables and cut-off values as those in the derivation cohort were applied to the validation cohort.

In total, 800 patients were identified; 62.5% [55/88] of patients with a maximum ACE Index of 3 did not respond to intravenous [IV] steroids (positive predictive value [PPV] 62.5%, negative predictive value [NPV] 79.8%). Furthermore, 79.8% [158/198] of patients with an ACE Index of 0 responded to IV steroids [PPV 79.8%, NPV 62.5%]. Receiver operator characteristic [ROC] curve analysis produced an area under the curve [AUC] of 0.663 [p < 0.001].

We have now reported and externally validated the ACE Index in acute colitis in a combined cohort of over 1000 patients from across the UK. The ACE Index may be used in conjunction with clinical judgement to help identify patients admitted with active UC who are at high risk of not responding to IV steroids. Further studies are required to improve objectivity and accuracy of assessment.

Background: Few studies have incorporated longitudinal assessments or used combinations of blood biomarkers as predictors of loss of response to biologic therapy for patients with Crohn's disease (CD) or ulcerative colitis (UC). Methods: This is a population-based cohort study comprising Danish patients with CD or UC from 2008 to 2018. We used logistic regression to analyze whether levels and changes in levels of C-reactive protein (CRP), serum albumin, and hemoglobin, routinely measured during a 14-week infliximab induction period, predicted a change to another biologic medication or cessation of biologic therapy. Results: During the induction period, 2883 (1626 CD, 1257 UC) patients had 12,730, 12,040, and 13,538 specimens with CRP, serum albumin, and hemoglobin, respectively. In all, 284 patients (9.9%) switched to another biologic medication, and 139 (4.8%) ceased biologic therapy in the follow-up period. Only the most recent CRP and hemoglobin levels predicted the efficacy of infliximab treatment at approximately 14 weeks, a time point when the clinician often determines whether to continue treatment. Conclusion: Measurement of blood biomarkers prior to the clinical assessment does not predict the effectiveness of infliximab.

Recently, a close association between ulcerative colitis (UC) and erectile dysfunction (ED) was reported. An inverse relationship between serum albumin and ED is found in patients with chronic disease. However, the association between serum albumin levels and ED in patients with UC is unclear. This study aims to investigate this issue in Japanese patients with UC.

One hundred and thirty-six Japanese male UC patients were enrolled in this study. Information on serum albumin levels and medications for UC from medical records, Sexual Health Inventory for Men (SHIM) score information from self-administered questionnaires and information on the severity of UC from physician reports were obtained from medical records, self-administered questionnaires, and reports from physicians. The participants were divided into tertiles based on the total protein, serum globulin, serum albumin, aspartate aminotransferase, and C-reactive protein levels. The definition of ED and severe ED was SHIM score < 22 and SHIM score < 8, respectively. The association between these serum markers and ED was assessed by multivariate logistic regression.

The prevalence of severe ED in the low, moderate, and high albumin groups was 66.0%, 51.0%, and 28.3%, respectively. After adjusting for confounding factors, the low albumin group was independently and positively associated with severe ED (adjusted odds ratio: 2.74, 95% confidence interval: 1.03-7.48, p for trend =0.044). No association between other marker and ED was found.

Serum albumin was independently inversely associated with severe ED in Japanese patients with UC. Hypoalbuminemia might be a useful complementary marker for assessing the prevalence and severity of ED in UC 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.

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.

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.

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.

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.

Risk factors for colectomy following an episode of acute severe ulcerative colitis (ASUC) have been well studied, but data examining the early complications following an episode is limited.

We aimed to evaluate the prevalence and risk factors for medical and surgical complications within 90 days of an ASUC admission and determine if a high-intensity induction infliximab dose is associated with these complications.

Retrospective analysis.

We conducted a retrospective study of ASUC admissions between January 2015 and July 2021 at a tertiary hospital. The primary outcome was the prevalence of total, medical and surgical complications within 90 days following an ASUC admission. Multivariate linear regression analysis assessed for factors associated with the prevalence of complications.

A total of 150 patients had 186 hospital admissions for ASUC. In total, 101/186 (54.3%) admissions required rescue medical therapy. Standard infliximab induction occurred in 65/100 admissions, accelerated infliximab induction in 35/100 and cyclosporine in 1/100 of admissions. In total, 117 complications, including 74/117 (63.2%) medical and 43/117 (36.8%) surgical complications, arose. Low serum albumin was independently associated with a higher incidence of total [β = -0.08 (95% confidence interval (CI): -0.15, -0.01), p = 0.03] and surgical complications [β = -0.1 (95% CI: -0.18, -0.001), p = 0.047], while an increased age was associated with increased incidence of surgical complications [β = 0.06 (95% CI: 0.01, 0.12), p = 0.02]. A higher Charlson score was associated with increased medical complications [β = 0.12 (95% CI: 0.01, 0.24), p = 0.03]. Infliximab induction dose intensity was not associated with an increased incidence of any complications.

Early complications following an ASUC admission is prevalent although the majority are not serious. Risk factors associated with complications include low serum albumin, older age and a higher comorbidity score. Induction infliximab dose intensity, however, is not a risk factor.