Acute Severe Ulcerative Colitis Research Articles

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.

Unveiling the Potential of JAK Inhibitors in Inflammatory Bowel Disease

Background: Janus kinase (JAK) inhibitors represent a novel class of oral therapies showing efficacy in treating ulcerative colitis (UC) and Crohn’s disease (CD), challenging conventional treatment paradigms. Summary: This review provides an overview of the potential novel uses of JAK inhibitors, focusing on their current approved indications and exploring possibilities beyond these indications. Tofacitinib and filgotinib are approved for UC, while upadacitinib is approved for both UC and CD. Additionally, their potential in acute severe UC, as steroid alternatives, and in managing fistulizing CD or extraintestinal manifestations are discussed. Key Message: JAK inhibitors play an important role in IBD (inflammatory bowel disease) treatment; however, clinicians must balance their promising efficacy with safety concerns. Individualized care and vigilance are essential for optimizing therapeutic benefits while mitigating potential adverse effects. Further research is necessary to clarify their efficacy, safety, and potential applications.

Ten missteps in the management of inflammatory bowel disease in Asia: An expert report by the Asian Pacific Association of Gastroenterology Working Group on Inflammatory Bowel Disease.

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.

Resolution of rectal bleeding by day 7 in acute severe ulcerative colitis is prognostic for post-discharge corticosteroid free clinical remission and endoscopic improvement

This study assesses two different disease activity measures, the MTWSI and the partial Mayo score, in hospitalized acute severe UC patients for prediction of post-discharge corticosteroid-free clinical remission and endoscopic improvement to help guide future considerations for disease activity assessment. In this post-hoc analysis from the TRIUMPH trial, these results suggest resolution of Mayo rectal bleeding sub-score may have high prognostic utility and could be considered as a primary endpoint for hospitalized UC trials. The study underscores the need for further research on patient-reported outcomes and endoscopic indices in larger populations for inpatient UC trials.

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

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

Effects of prednisolone tapering on effectiveness of infliximab in patients with ulcerative colitis: data from a retrospective cohort

Background and objectiveThe influence of concomitant prednisolone on clinical outcomes and safety in infliximab-treated ulcerative colitis (UC) patients is unknown.Design, setting, participants and outcome measuresA retrospective cohort study was performed,...

Safety and Efficacy of Inpatient Infliximab Rescue Therapy for Acute Crohn's Disease Flares.

Describe the safety, complications, and need for urgent surgery in patients requiring inpatient rescue infliximab for acute Crohn's disease (CD) flare. Infliximab is increasingly used for patients hospitalized with acute severe ulcerative colitis as rescue therapy; however, optimal management for patients hospitalized for CD flares remains unclear. A single-institution retrospective study of patients aged 18+ admitted from 2008 to 2020 with acute Crohn's flare requiring induction of rescue infliximab therapy. Outcomes included postoperative and medication-related complications and need for urgent surgery. 52 patients were included in analysis; 8% required surgery on index admission, and 19% required surgery within 90 days of infliximab. Postoperative complications included 1 anastomotic leak, 3 superficial wound infections, 3 prolonged ileus, and 1 urinary infection. There were no adverse reactions to infliximab infusion, and medical complication rates were low. Patients with penetrating disease were more likely to undergo surgery within 90 days of infliximab (43% vs 8%; P = .01). Mean LOS was longer for patients undergoing surgery within 90 days of therapy compared to those who did not (13.4 vs 8.3days, P = .04). Inpatient rescue infliximab is safe for treating acute Crohn's disease flare in addition to standard steroid therapy. The majority of patients hospitalized with Crohn's flare requiring rescue infliximab avoided surgery with low postoperative and medication-related complications. More research is needed to clarify the optimal rescue infliximab therapy dosage.

Post-hospitalization Short Versus Long Steroid Taper Strategies in Patients With Acute Severe Ulcerative Colitis: A Comparison of Clinical Outcomes.

Ulcerative colitis (UC) is a chronic inflammatory colon disease characterized by relapsing flares and remission episodes. However, the optimal steroid tapering strategy in patients hospitalized for acute severe UC (ASUC) remains relatively unknown. We aim to examine the clinical outcomes in patients hospitalized for ASUC regarding variable prednisone taper regimens upon discharge. We retrospectively reviewed all adult patients admitted to our facility with ASUC between 2000 and 2022. Patients were divided into 2 groups based on the duration of steroid taper on discharge (< 6 and > 6 weeks). Patients who had colectomy at index admission were excluded from the analysis. The primary outcome was rehospitalization for ASUC within 6 months of index admission. Secondary outcomes included the need for colectomy, worsening endoscopic disease extent and/or severity during the follow-up period (6 months), and a composite outcome as a surrogate of worsening disease (defined as a combination of all products above). Two-sample t-tests and Pearson's chi-square tests were used to compare the means of continuous and categorical variables, respectively. Multivariate logistic regression analysis was performed to identify independent predictors for rehospitalization with ASUC. A total of 215 patients (short steroid taper = 91 and long steroid taper = 124) were analyzed. A higher number of patients in the long steroid taper group had a longer disease duration since diagnosis and moderate-severe endoscopic disease activity (63.8 vs. 25.6 months, p < 0.0001, 46.8% vs. 23.1%, P = ≤ .05, respectively). Both groups had similar disease extent, prior biologic therapy, and the need for inpatient rescue therapy. At the 6-month follow-up, rates of rehospitalization with a flare of UC were comparable between the 2 groups (68.3% vs. 68.5%, P = .723). On univariate and multivariate logistic regression, escalation of steroid dose within four weeks of discharge (aOR 6.09, 95% CI: 1.82-20.3, P = .003) was noted to be the only independent predictor for rehospitalization with ASUC. This is the first study comparing clinical outcomes between post-discharge steroid tapering regimens in hospitalized patients for ASUC. Both examined steroid taper regimens upon discharge showed comparable clinical results. Hence, we suggest a short steroid taper as a standard post-hospitalization strategy in patients following ASUC encounters. It is likely to enhance patient tolerability and reduce steroid-related adverse effects without adversely affecting outcomes.

Clinical utility of C-reactive protein-to-albumin ratio in the management of patients with inflammatory bowel disease.

C-reactive protein (CRP)-to-albumin ratio (CAR) is a novel score with prognostic value in inflammatory conditions. This study assessed the performance of CAR as an objective marker of disease activity and prediction of subtherapeutic infliximab trough levels in patients with inflammatory bowel disease (IBD). A retrospective study was conducted on three different patient cohorts with IBD: patients who had (i) fecal calprotectin (FC) measurements; (ii) Mayo Endoscopic Scores; and (iii) infliximab trough levels available. The relative performances of CAR, albumin, and CRP were compared in predicting disease activity (based on FC or Mayo Endoscopic Score) and infliximab trough levels. In both the FC (n = 289) and endoscopy (n = 65) cohorts, albumin and CAR correlated with objective disease activity. CAR (area under the curve [AUC] 0.70) was only marginally better at detecting active disease, measured by FC, compared to CRP (AUC 0.68). A CAR >0.15 was able to detect Mayo 3 disease (AUC 0.83, sensitivity 81%, specificity 89%). Albumin (r = 0.38) and CAR (r = -0.42) correlated with infliximab trough levels (n = 204). The optimal CAR for detecting subtherapeutic infliximab trough levels was >0.08 (AUC 0.70, sensitivity 66%, specificity 64%). Both albumin and CAR were independent predictors of subtherapeutic infliximab trough levels but correlated poorly with infliximab trough levels longitudinally in the same patient. CAR was only a modest discriminator of subtherapeutic infliximab levels and offers little more than CRP in detecting active disease. CAR has potential to detect severe Mayo 3 disease and could be calculated in patients admitted with suspected acute severe ulcerative colitis.

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

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. 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 40mg/L. She also received 1 dose of vedolizumab. Hyperbaric treatments were offered but declined. By HD5, she was clinically improved, with a CRP of 9mg/L. She was transitioned from IV to oral steroids. After starting oral steroids her symptoms relapsed, her CRP increased from 9 to 48mg/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. 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.

Effectiveness and safety of a third-line rescue treatment for acute severe ulcerative colitis refractory to infliximab or ciclosporin (REASUC study).

The advent of new therapeutic agents and the improvement of supporting care might change the management of acute severe ulcerative colitis (ASUC) and avoid colectomy. To evaluate the colectomy-free survival and safety of a third-line treatment in patients with ASUC refractory to intravenous steroids and who failed either infliximab or ciclosporin. Multicentre retrospective cohortstudy of patients with ASUC refractory to intravenous steroids who had failed infliximab or ciclosporin and received a third-line treatment during the same hospitalisation. Patients who stopped second-line treatment due to disease activity or adverse events (AEs) were eligible. We assessed short-term colectomy-free survival by logistic regression analysis. Kaplan-Meier curves and Cox regression models were used for long-term assessment. Among 78 patients, 32 received infliximab and 46 ciclosporin as second-line rescue treatment. Third-line treatment was infliximab in 45 (58%), ciclosporin in 17 (22%), tofacitinib in 13 (17%) and ustekinumab in 3 (3.8%). Colectomy was performed in 29 patients (37%) during follow-up (median 21 weeks). Of the 78 patients, 32 and 18 were in clinical remission at, respectively, 12 and 52 weeks. At the last visit, 25 patients were still on third-line rescue treatment, while 12 had stopped it due to clinical remission. AEs were reported in 26 (33%) patients. Two patients died (2.6%), including one following colectomy. Third-line rescue treatment avoided colectomy in over half of the patients with ASUC and may be considered a therapeutic strategy.

Novel medical strategies in acute severe ulcerative colitis

Novel medical strategies in acute severe ulcerative colitis

Acute Severe Ulcerative Colitis Flare Complicated by Myopericarditis and Infliximab-Induced Hepatitis.

In acute inflammatory bowel disease (IBD) flare presentation with tachycardia and chest pain, an underlying myocardial injury should be investigated.Mucosal healing should be evaluated endoscopically in cases of partial response to biologics.Both cytomegalovirus (CMV) infection and infliximab-induced liver injury may lead to acute hepatitis.

Clinical Outcomes at 8-16 Weeks After Upadacitinib Initiation for Acute Severe Ulcerative Colitis: A Case Series in the United States.

Lay Summary In 9 patients hospitalized for acute severe ulcerative colitis, 8 were successfully discharged without the need for colectomy. Six of 7 patients with sufficient follow-up achieved steroid-free clinical remission at 8 to 16 weeks, and 1 of 2 patients achieved endoscopic response.

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.

Antibiotics for inflammatory bowel disease: Current status.

There is abundant literature reporting about the use of antibiotics in inflammatory bowel disease (IBD), but their role in the management of IBD is not entirely clear. Diverse infectious organisms have been implicated in the pathogenesis of Crohn's disease. Also, infections are believed to be a trigger for flares of ulcerative colitis. The benefit of the routine use of antibiotics in IBD is equivocal. However, there are certain situations, where antibiotics have a clear role and evidence of benefit: perianal fistula, intra-abdominalabscesses in Crohn's disease, acute pouchitis and infection-related flares. However, there is a lack of supportive evidence for the routine use of antibiotics in all disease-related flares. Evidence indicates a lack of benefit of intravenous antibiotics in acute severe ulcerative colitis and only limited benefit in active ulcerative colitis. Limited evidence suggests the role of a combination of oral antibiotics in pediatric ulcerative colitis. Certain targeted antibiotic regimens have been used in IBD. In ulcerative colitis, limited evidence suggests the benefit of the use of an antibiotic cocktail directed against Fusobacterium varium. Therapy directed against Escherichia coli does not seem to have a benefit in inflammatory Crohn's disease. In Crohn's disease, antimycobacterial therapy may result in symptomatic improvement but no durable benefit. Antitubercular therapy (ATT), on the contrary, may result in fibrotic transformation, suggesting a need to avoid misdiagnosis and limit the duration of ATT in Crohn's disease. This review assesses the published literature with respect to antibiotic use and provides guidance to clinicians in appropriate antibiotic use in various situations in the setting of IBD.

Evaluation of the Factors Associated with Post-Operative Outcome in Patients of Ulcerative Colitis Undergoing Ileal Pouchanal Anastomosis with Comparison of Functional Outcome between Stapler and Hand-Sewn Anastomosis

ntroduction Ulcerative colitis defined as a non-granulomatous idiopathic inflammatory disease which mainly affects the colon and rectum. The disease may arise at any age but most commonly affects the adults between the age group of 30–40 years.1,2. The etiology of the disease is multifactorial, involving genetic predisposition, dysregulated immune responses, epithelial barrier defects and environmental factors. No sex predilection is seen in ulcerative colitis.3,5 The peak age of onset of disease is between 30 to 40 years.4,6 The environmental factors has also been found to play an important role in the etiopathogenesis of ulcerative colitis. Cigarette smoking is one of the major factor associated with ulcerative colitis, non-smokers have a milder disease course and active smokers are less likely to develop ulcerative colitis7 Appendectomy also confers a protective effect against ulcerative colitis, especially in young patients operated for acute appendicitis.8. Classic findings in endoscopy in patients with ulcerative colitis include loss of normal vascular pattern, erythema, erosions, granularity, friability, ulcerations and bleeding9 . The primary aim of medical management is to induce and maintain remission with the long-term goals of improving quality of life and prevent disability. Absolute indications for surgery include uncontrolled hemorrhage, perforation, and colorectal carcinoma or dysplastic lesions not amenable to endoscopic removal.10 Surgery is also indicated in refractory acute severe ulcerative colitis or medically refractory disease. The most commonly performed surgery for ulcerative colitis is restorative proctocolectomy with ileal pouchanal anastomosis (IPAA). An important aspect of the surgery is the use of either sutures or staplers for anastomosis. Two types of ileal pouch-anal anastomosis (IPAA) have been described: a mucosectomy of the rectal stump followed by a hand-sewn ileal pouch-anal anastomosis.11 The alternative technique is to retain the mucosa of the rectal stump and perform a stapled pouch-anal anastomosis.

Effectiveness of Upadacitinib for Patients With Acute Severe Ulcerative Colitis: A Multicenter Experience.

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

Medical treatment selection and outcomes for hospitalized patients with severe ulcerative colitis as defined by the Japanese criteria.

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 28days. 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.

HIGH COPY NUMBER POLYMORPHISMS OF ALPHA DEFENSIN 1-3 ARE ASSOCIATED WITH THERAPEUTIC RESPONSIVENESS IN INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND AND PURPOSE Prednisolone therapy is the first choice for the treatment of acute severe ulcerative colitis (ASUC), however, the refractory case is sometimes observed. Alpha defensin 1-3 (DEFA1A3) stored in neutrophils acts as an effector factor of innate immunity. It has been reported that the copy number variation of the DEFA1A3 gene is associated with the severity of ulcerative colitis (UC). However, the impact of DEFA1A3 in response to treatment have not been fully investigated. Therefore, we aimed to clarify the relationship between the number of DEFA1A3 copies and UC prednisolone treatment response. SUBJECTS AND METHODS Patients with UC who had attended our department and related facilities and had the number of DEFA1A3 copies measured were included between 2020 and 2022. The number of DEFA1A3 copies were measured using droplet digital PCR after DNA extraction from peripheral blood mononuclear cells. Mayo score was used to determine the response to prednisolone and severity of UC. ASUC was defined as presence of more than 6 bloody stools/d along with any one of the following: pulse rate&amp;gt; 90 bpm, temperature &amp;gt; 37.8 °C, hemoglobin &amp;lt; 10.5 g/dL, and/or CRP &amp;gt; 30mg/L. Clinical background and various parameters were extracted from medical record information. RESULTS The 47 ASUC patients were included in the study. The median DEFA1A3 copy number of the patients was 9, the median DEFA1A3 copy number in ASUC was higher than that in healthy subjects. The DEFA1A3 copy number was significantly higher in the non-remission group than in the remission group after treatment with prednisolone.There were no differences in other parameters such as CRP and WBC between the two groups. CONCLUSION DEFA1A3 copy number may be a predictive marker of prednisolone treatment response.