Ulcerative colitis is a common chronic inflammatory disease of the colon and rectum, resulting from a dysregulated immune response towards intraluminal antigens in a genetically predisposed host. The ...disease has a varying extent and severity. Approximately 20% of patients with ulcerative colitis experience a severe flare during the course of their disease, requiring hospitalization. Acute severe ulcerative colitis (ASUC) is potentially a life-threatening condition that requires early recognition, hospitalization, correction of body fluids and electrolytes, and nutritional support if needed. Superimposed bacterial or viral infections need to be excluded and thromboprophylaxis should be started. Intravenous corticosteroids are the first-line treatment for this condition. Rescue treatment with ciclosporin or infliximab is indicated in patients who do not sufficiently respond to corticosteroids after 3-5 days, with close monitoring of the patients' symptoms, serum C-reactive protein and albumin levels. If medical therapy fails, timely colectomy should be performed to prevent critical complications. In this article, we review all relevant aspects of ASUC, from its pathophysiological background to modern management in clinical practice.
Background and Aims
Biosimilar approval, such as Inflectra™ (CT-P13) for treating ulcerative colitis (UC) and Crohn’s disease (CD), has reduced direct drug costs. Though clinicians are comfortable ...with biosimilar use in treatment-naïve patients, there are concerns in some jurisdictions that there are insufficient data from well-controlled trials to support non-medical switching. A systematic review, along with a critical assessment of the study design, was conducted to assess the potential impact of switching stable CD/UC patients from infliximab to CT-P13.
Methods
A literature search using PubMed and abstracts/posters from 3 major gastroenterology conferences from 2014 to 2018 was completed. Two individual reviewers extracted data from each relevant report and compiled it into evidence tables to facilitate descriptive analyses. Key randomized trial and observational study designs were critically assessed to contextualize data relevance.
Results
A total of 49 reports (3 randomized controlled trials, 40 observational trials, and 1 case series) were included. Most studies revealed no efficacy, safety, or immunogenicity concerns with non-medical switch. Limitations of supporting data include a small number of randomized controlled trials; predominance of observational studies with varying outcome assessments and lack of appropriate controls; and scarcity of research on biosimilar switch long-term effects.
Conclusions
The majority of studies suggested non-medical switch is safe. However, clinicians and regulatory bodies should be aware of differences and limitations in study designs when making inferences about the risks and benefits of switching stable IBD patients to biosimilars.
Background
Hyperbaric oxygen therapy (HBOT) improves short-term outcomes for ulcerative colitis (UC) patients hospitalized for acute flares. Longer-term impacts and cost-effectiveness are unknown.
...Methods
We compared disease outcomes and cost-effectiveness of HBOT in addition to standard of care versus standard of care alone for UC patients hospitalized for acute flares using a microsimulation model. Published literature was used for transition probabilities, costs, and quality-adjusted life year (QALY) estimates. We modeled 100,000 individuals in each group over a 5-year horizon and compared rates of re-hospitalization, rescue medical therapy, colectomy, death, and cost-effectiveness at a willingness-to-pay of $100,000/QALY. Probabilistic sensitivity analyses were performed with 500 samples and 250 trials, in addition to multiple microsimulation sensitivity analyses.
Results
The use of HBOT at the time of index hospitalization for an acute UC flare is projected to reduce the risk of re-hospitalization, inpatient rescue medical therapy, and inpatient emergent colectomy by over 60% (
p
< 0.001) and mortality by over 30% (
p
<0.001), during a 5-year horizon. The HBOT strategy costs more ($5600 incremental cost) but also yielded higher QALYs (0.13 incremental yield), resulting in this strategy being cost-effective ($43,000/QALY). Results were sensitive to HBOT costs and rates of endoscopic improvement with HBOT. Probabilistic sensitivity analyses observed HBOT to be more cost-effective than standard of care in 95% of iterations.
Conclusion
The use of HBOT to optimize response to steroids during the index hospitalization for an acute UC flare is cost-effective and is projected to result in significant reductions in disease-related complications in the long term.
Rapidity of symptom resolution informs treatment choice in patients with moderate-severe ulcerative colitis (UC). We conducted a systematic review and network meta-analysis comparing early ...symptomatic remission with approved therapies.
Through a systematic literature review to December 31, 2022, we identified randomized trials in adult outpatients with moderate-severe UC treated with approved therapies (tumor necrosis factor α antagonists, vedolizumab, ustekinumab, janus kinase inhibitors, or ozanimod), compared with each other or placebo, reporting rates of symptomatic remission (based on partial Mayo score, with resolution of rectal bleeding and near-normalization of stool frequency) at weeks 2, 4, and/or 6. We performed random-effects network meta-analysis using a frequentist approach and estimated relative risk (RR) and 95% confidence interval values.
On network meta-analysis, upadacitinib was more effective than all agents in achieving symptomatic remission at weeks 2 (range of RR, 2.85-6.27), 4 (range of RR, 1.78-2.37), and 6 (range of RR, 1.84-2.79). Tumor necrosis factor α antagonists and filgotinib, but not ustekinumab and vedolizumab, were more effective than ozanimod in achieving symptomatic remission at week 2, but not at weeks 4 and 6. With approximately 10% placebo-treated patients achieving symptomatic remission at 2 weeks, we estimated 68%, 22%, 23.7%, 23.9%, 22.2%, 18.4%, 15.7%, and 10.9% of upadacitinib-, filgotinib-, infliximab-, adalimumab-, golimumab-, ustekinumab-, vedolizumab-, and ozanimod-treated patients would achieve early symptomatic remission, ustekinumab and vedolizumab achieving rapid remission only in biologic-naïve patients.
In a systematic review and network meta-analysis, upadacitinib was most effective in achieving early symptomatic remission, whereas ozanimod was relatively slower acting.
Crohn’s disease and ulcerative colitis are heterogeneous inflammatory bowel diseases, and therapeutic requirements vary among patients. We have a limited capacity to predict disease progression for ...individual patients, therefore it is important that they are evaluated for the presence of active disease when symptoms are mild or even absent, when patients are more likely to respond to new treatment interventions. It then is important to monitor responses to treatment, to quickly identify those therapies that are ineffective, modify or change therapy, and avoid disease complications. Studies are underway to assess the effects of different monitoring strategies. Because of the heavy burden of severe inflammatory bowel disease on patients’ health and quality of life, and the association between intestinal healing and disease progression in high-risk patients, a treat-to-target strategy (based on tissue healing) is likely to be optimal.
To assess the safety of early vs late biologic switch in patients with inflammatory bowel disease.
In this retrospective study, we included patients with inflammatory bowel disease who underwent ...biologic switch between January 2014 and July 2022 at a tertiary center. The primary outcome was any infection by 6 months.
There was no statistically significant difference between patients who had early biologic switch (≤30 days, n = 51) and late switch (>30 days, n = 77) in either infectious or noninfectious adverse events by 6 and 12 months.
Early biologic switch is safe. A prolonged washout period between 2 biologics is unnecessary.
One quarter of patients with ulcerative colitis will develop a severe acute exacerbation of disease during their lifetime. Despite high dose corticosteroids, half of these patients will fail ...subsequent medical rescue therapy, and half will require colectomy within 5 years. Dulai and colleagues report the results of a fascinating, double blind, sham controlled, proof of concept trial which demonstrated that administration of short term hyperbaric oxygen therapy (HBOT) at the point of presentation with severe UC was able to rapidly induce short term remission and avoid the need for urgent second line medical rescue therapy. Further dose finding studies are underway.
This is the first UK national guideline to concentrate on acute lower gastrointestinal bleeding (LGIB) and has been commissioned by the Clinical Services and Standards Committee of the British ...Society of Gastroenterology (BSG). The Guidelines Development Group consisted of representatives from the BSG Endoscopy Committee, the Association of Coloproctology of Great Britain and Ireland, the British Society of Interventional Radiology, the Royal College of Radiologists, NHS Blood and Transplant and a patient representative. A systematic search of the literature was undertaken and the quality of evidence and grading of recommendations appraised according to the GRADE(Grading of Recommendations Assessment, Development and Evaluation) methodology. These guidelines focus on the diagnosis and management of acute LGIB in adults, including methods of risk assessment and interventions to diagnose and treat bleeding (colonoscopy, computed tomography, mesenteric angiography, endoscopic therapy, embolisation and surgery). Recommendations are included on the management of patients who develop LGIB while receiving anticoagulants (including direct oral anticoagulants) or antiplatelet drugs. The appropriate use of blood transfusion is also discussed, including haemoglobin triggers and targets.
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