Medical Therapy For Ulcerative Colitis Research Articles

P0264 Using a machine learning model to grade clip-level endoscopic inflammation reveals the heterogeneity of mucosal inflammation in ulcerative colitis

Abstract Background Endoscopic assessment of inflammation in ulcerative colitis (UC) is a therapeutic endpoint in clinical trials1 but can be limited by inter- and intra-observer variability2 and lack of sensitivity to detect the degree of inflammation throughout the colon3. We used a machine learning (ML) model to grade inflammation of full-length endoscopy videos at the clip-level (a series of smaller segments of video) in order to evaluate the uniformity of mucosal inflammation. Methods We used a previously developed ML model that predicts the endoscopy subscore4, a component of the modified Mayo Score, and applied it to 49 full-length endoscopy videos randomly selected and stratified by endoscopic severity from the Phase 3 induction trial for mirikizumab in UC (NCT03518086). A human reviewer identified the point of maximal extent and the end of the procedure to isolate the withdrawal portion of the video which was then divided into 15, 30, or 60 second clips, and the model generated an endoscopy subscore for each clip (clip-level endoscopy subscore) and for the entire video (video-level endoscopy subscore). Variability of inflammation between clips were calculated. Results Assessment of the endoscopy subscore on individual video clips during withdrawal demonstrated a patchy distribution of inflammation severity, and this was consistent regardless of the video-level endoscopic severity (Fig. 1). Notably, the segment with the most severe inflammation did not always occur proximally (Fig. 1). The variability of inflammation was greater in 15-second (Fig. 1A) than 30-second (Fig. 1B) or 60-second (Fig. 1C) clips. Video-level endoscopy subscores of 1-3 did contain the spectrum of clip-level endoscopy subscore grades of 0-3, but the greatest proportion of clips correlated with the video-level endoscopy subscore (Fig. 2). Conclusion Using a novel ML model to determine video-level and clip-level endoscopy subscores using colonoscopy videos in patients with moderate-to-severe UC, we identify heterogeneity of inflammatory activity, and this was best observed with clips at 15-second intervals. These findings provide insight into inter- and intra-rater variability of endoscopy subscore assessments by human readers and highlight relevant data that are not captured by a single video-level score. Further study is needed to optimize assessment of inflammation in this setting. References Food and Drug Administration. Ulcerative Colitis: Developing Drugs for Treatment [Internet]. 2022 [cited 2024 Oct 17]. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/ulcerative-colitis-developing-drugs-treatment Hashash, J. G., Yu Ci Ng, F., Farraye, F. A., Wang, Y., Colucci, D. R., Baxi, S., . . . & Melmed, G. Y. (2024). Inter-and intraobserver variability on endoscopic scoring systems in crohn’s disease and ulcerative colitis: A systematic review and meta-analysis. Inflammatory Bowel Diseases, izae051. Vuyyuru, S. K., Ma, C., Nguyen, T. M., Zou, G., Peyrin-Biroulet, L., Danese, S., . . . & Jairath, V. (2024). Differential efficacy of medical therapies for ulcerative colitis according to disease extent: Patient-level analysis from multiple randomized controlled trials. EClinicalMedicine, 72. Rubin, D. T., Gottlieb, K., Colombel, J. F., Schott, J. P., Erisson, L., Prucka, B., . . . & McGill, J. (2023). Development of a novel ulcerative colitis endoscopic mayo score prediction model using machine learning. Gastro Hep Advances, 2(7), 935-942.

US National Estimates of Contemporary Mortality Rates in Patients With Ulcerative Colitis Undergoing Colectomy.

Despite a growing armamentarium of medical therapies for ulcerative colitis, colectomy remains an important therapeutic option. To better inform shared decision-making about surgery, we estimated the contemporary risk of mortality after colectomy. Mortality rates were estimated using the National Inpatient Sample (2016-2020). Factors associated with postcolectomy death were evaluated in multivariable regression. Postcolectomy mortality occurred in 1.2% (95% CI: 0.8%, 1.9%) of hospitalizations. Comorbidity burden, emergent laparotomy, and delays to surgery >5 days after admission were associated with mortality. Colectomy may be associated with mortality; however, this risk is heterogeneous based on patient- and procedural-related factors.

Differential efficacy of medical therapies for ulcerative colitis according to disease extent: patient-level analysis from multiple randomized controlled trials

Disease extent in Ulcerative Colitis (UC) has prognostic implications for disease course. It is unclear whether the efficacy of medical therapies for moderate to severely active UC vary according to disease extent at enrollment. We analyzed patient level data from 11 Phase 2 and 3 clinical trials of advanced therapies in patients with moderate-to-severe UC to assess modifications of advanced therapy effects by disease extent. Primary outcome was clinical response and secondary outcomes were clinical remission, endoscopic response/remission and endoscopic improvement, and Mayo clinic subscore for both induction and maintenance studies. Binary and continuous outcomes were analyzed using the modified Poisson regression model and the mixed-effects model, respectively, adjusting for age, sex, disease duration, concomitant steroid use and prior anti-TNF use. Effect modifications with binary outcomes were quantified by ratios of risk ratio for left-sided to that for extensive colitis while effect modifications with the Mayo subscores were quantified by differences of the differences between mean scores of the left-sided and extensive colitis. Results were presented with point estimates and 95% confidence intervals as well as p-values. Eleven clinical trials enrolling 5450 UC patients (infliximab=2, adalimumab=2, golimumab=2, vedolizumab=2, tofacitinib=3) were included. In induction trials, there was evidence to suggest effect modification by disease extent for clinical response with tofacitinib (the ratio of RRs 0.67, 95% CI [0.45, 0.99], p=0.049) and clinical remission with infliximab (ratio of RRs 0.33, 95% CI [0.13, 0.85], p=0.020) favoring patients with extensive colitis. There was no evidence to suggest effect modification for endoscopic improvement and clinical outcomes. There was evidence to suggest effect modification by disease extent for clinical remission with tofacitinib (ratio of RRs 0.44, 95% CI [0.22, 0.89], p=0.020) favoring patients with extensive colitis. For symptom subscores from the Mayo Clinic score, tofacitinib was associated with a greater reduction in both stool frequency (difference of differences 0.37, 95% CI [0.08, 0.65], p=0.012) and rectal bleeding scores (difference of differences 0.25, 95% CI [0.03, 0.47], p=0.026) in patients with extensive colitis compared to left sided. These findings underscore the possibility of differential efficacy of medical therapies according to disease distribution. These results warrant further exploration in forthcoming trials to better inform treatment strategies and consideration of disease distribution as a baseline stratification factor in clinical trials. This study did not receive any financial support.

S917 Effectiveness and Safety of Weight Loss Medical Therapy in Ulcerative Colitis

S917 Effectiveness and Safety of Weight Loss Medical Therapy in Ulcerative Colitis

Ulcerative Colitis: Current and Emerging Treatment Strategies.

Historically, medical therapy for ulcerative colitis (UC) was limited to corticosteroids. Excitingly, over the past just 1–2 decades, the options for medical therapy have expanded and include biologics and small molecules, with more agents actively being developed. In this article, we review the current and emerging treatment strategies for UC stratified according to disease severity.

Pediatric ulcerative colitis: three- versus two-stage colectomy with ileal pouch-anal anastomosis.

Despite advancements in medical therapy for ulcerative colitis (UC), a significant proportion of children progress to colectomy with ileal pouch-anal anastomosis (IPAA). Procedural related complications between two- and three-stage operations in children have not been well described. We performed a retrospective review of patients who underwent a colectomy for UC or inflammatory bowel disease unclassified between 2008 and 2018. Forty-nine children underwent an IPAA at the time of colectomy (two stage) or during a subsequent operation (three stage). Preoperative hemoglobin and albumin concentrations were lower among those undergoing three-stage procedures. The rate of early complications (≤30days) was similar between the two groups (p = 0.46); however, late complications (>30days) were more commonly associated with three-stage procedures (p = 0.03). Time with a stoma was 3.2months longer among those who underwent a three-stage procedure. While three-stage procedures were more often performed during the first half of the study period (2008-2012), two-stage procedures became more common during the second half (2013-2018). During this transition to favor two-stage procedures, complication rates did not significantly change. Although three-stage procedures were thought to be associated with fewer complications, we found comparable complication rates as we transition to two-stage procedures.

Mo1824 – Histologic Healing Rates of Medical Therapies for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Mo1824 – Histologic Healing Rates of Medical Therapies for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Histologic Healing Rates of Medical Therapies for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Histologic remission is a potentially valuable means of assessing disease activity and treatment response in ulcerative colitis (UC). However, the efficacy of existing therapies to achieve this outcome is unclear. We performed a systematic review and meta-analysis of histologic outcomes in UC randomized controlled trials and examined the relationship between histologic and endoscopic outcomes. MEDLINE, EMBASE, CENTRAL, and the Cochrane IBD Register were searched for randomized controlled trials of aminosalicylates, corticosteroids, immunosuppressives, biologics, and small molecules. Histologic and endoscopic remission and response data were independently extracted and pooled using binomial-normal random-effect or fixed-effect models. Pooled efficacy estimates were calculated as risk ratios (RRs) using the Mantel-Haenszel method. Univariable and multivariable random-effect meta-regression models examined factors associated with histologic remission. Seventy-four studies (68 induction and 7 maintenance) were identified. Topical aminosalicylate enemas [37.2%, 95% confidence interval (CI), 29.0-46.3] and suppositories (44.9%, 95% CI, 28.9-62.3) had the highest induction of histologic remission rates. Aminosalicylate enemas (RR = 4.14, 95% CI, 2.35-7.31), aminosalicylate suppositories (RR = 3.94, 95% CI, 1.26-12.32), and budesonide multimatrix (RR = 1.47, 95% CI 1.08-1.99) had higher histologic remission rates than placebo. Data were lacking for biologics and immunosuppressives. The pooled histologic remission rate for placebo in induction studies was 10.4% (95% CI, 7.1-15.2). Histologic and endoscopic remission correlated strongly (r = 0.66; 95% CI, 0.50-0.78). In multivariate analysis of placebo-arm data, less severe clinical disease activity and corticosteroid use were associated with higher histologic remission rates. Similarly, mild clinical disease activity was associated with higher histologic remission rates when active-arm data were analyzed. Histologic remission rates for current UC treatments ranged from 15.0% to 44.9% according to drug class and patient population with the highest rates observed for topical aminosalicylates. Placebo remission rates were low with relatively narrow CIs. These data provide benchmarks to inform future trial design. Histologic remission is a potential treatment target in clinical practice.

Factors affecting clinical decision-making in inflammatory bowel disease and the role of point-of-care calprotectin.

Objectives:Patient-reported symptoms correlate poorly with mucosal inflammation. Clinical decision-making may, therefore, not be based on objective evidence of disease activity. We conducted a study to determine factors associated with clinical decision-making in a secondary care inflammatory bowel disease (IBD) population, using a cross-sectional design.Methods:Decisions to request investigations or escalate medical therapy were recorded from outpatient clinic encounters in a cohort of 276 patients with ulcerative colitis (UC) or Crohn’s disease (CD). Disease activity was assessed using clinical indices, self-reported flare or faecal calprotectin ≥ 250 µg/g. Demographic, disease-related and psychological factors were assessed using validated questionnaires. Logistic regression was performed to determine the association between clinical decision-making and symptoms, mucosal inflammation and psychological comorbidity.Results:Self-reported flare was associated with requesting investigations in CD [odds ratio (OR) 5.57; 95% confidence interval (CI) 1.84–17.0] and UC (OR 10.8; 95% CI 1.8–64.3), but mucosal inflammation was not (OR 1.62; 95% CI 0.49–5.39; and OR 0.21; 95% CI 0.21–1.05, respectively). Self-reported flare (OR 7.96; 95% CI 1.84–34.4), but not mucosal inflammation (OR 1.67; 95% CI 0.46–6.13) in CD, and clinical disease activity (OR 10.36; 95% CI 2.47–43.5) and mucosal inflammation (OR 4.26; 95% CI 1.28–14.2) in UC were associated with escalation of medical therapy. Almost 60% of patients referred for investigation had no evidence of mucosal inflammation.Conclusions:Apart from escalation of medical therapy in UC, clinical decision-making was not associated with mucosal inflammation in IBD. The use of point-of-care calprotectin testing may aid clinical decision-making, improve resource allocation and reduce costs in IBD.

Mortality associated with medical therapy in ulcerative colitis.

Mortality associated with medical therapy in ulcerative colitis.

Medical Therapy of Ulcerative Colitis

Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease (IBD) characterized by continuous colonic mucosal inflammation that extends proximally from the rectum. Most patients present with bloody diarrhea, abdominal pain, tenesmus, and urgency. The course of UC is characterized by periods of flares and remission, and can significantly impact quality of life. Most patients are successfully treated medically, though 15 to 25% of patients require total proctocolectomy. Treatment of UC depends on the extent and severity of the disease, and response to prior therapies. This review outlines the medical treatment of UC and the therapies available for the induction and maintenance of remission. Figures include endoscopic and histologic images of UC, and algorithms cover outpatient inductions for mild-to-moderate disease and moderate-to-severe-disease, outpatient management of known steroid-refractory/steroid-intolerant patient, and approach to inpatient management of acute severe UC. Tables list disease severity by Truelove and Witts criteria, IBD medication adverse effects and monitoring parameters, induction dosing of 5-aminosalicylates, and rates of clinical response, remission, and mucosal healing in patients receiving anti-tumor necrosis factor (TNF) agents versus placebo by trial. This review contains 5 highly rendered figures, 4 tables, and 118 references.

Surgical management of acute ulcerative colitis.

The medical therapy of ulcerative colitis (UC) has improved significantly allowing many patients to defer or avoid surgery. Despite this about 25% of patients with inflammatory bowel disease (IBD) complicated by acute colitis undergo emergency colectomy. Emergency colectomy is needed in acute severe colitis unresponsive to medical management and for life threatening complications like toxic megacolon, perforation and severe hemmorhage. Most important predictive factor for postoperative morbidity and mortality after colectomy is the timing of surgery. Prolonged unsuccessful medical treatment will delay surgery and increase the risk of postoperative complications in these seriously ill, immunocompromised, malnourished, and deteriorating patients.

Colonoscopic evaluation in ulcerative colitis.

Colonoscopic evaluation is an important tool in the evaluation of ulcerative colitis (UC). UC is divided by disease extent into proctitis, proctosigmoiditis, left-sided colitis, and pan-colitis. In addition, a cecal or peri-appendiceal patch and backwash ileitis are associated with UC. The extent and behavior of UC has been characterized further using various indices and scoring systems; among these systems is the Mayo Score, which is widely used in current clinical trials for new medications. As these medical therapies for UC have developed, achieving mucosal healing with medications has become an important therapeutic objective.

Treat To Target Deep Remission with Mucosal Healing: New Goals of Medical Therapy in Ulcerative Colitis

Treat To Target Deep Remission with Mucosal Healing: New Goals of Medical Therapy in Ulcerative Colitis

Patient Preferences for Surgical Versus Medical Therapy for Ulcerative Colitis

Therapy options for mesalamine-refractory ulcerative colitis (UC) include immunosuppressive medications or surgery. Chronic immunosuppressive therapy increases risks of infection and cancer, whereas surgery produces a permanent change in bowel function. We sought to quantify the willingness of patients with UC to accept the risks of chronic immunosuppression to avoid colectomy. We conducted a state-of-the-art discrete-choice experiment among 293 patients with UC who were offered a choice of medication or surgical treatments with different features. Random parameters logit was used to estimate patients' willingness to accept trade-offs among treatment features in selecting surgery versus medical treatment. A desire to avoid surgery and the surgery type (ostomy versus J-pouch) influenced patients' choices more than a specified range of 10-year mortality risks from lymphoma or infection, or disease activity (mild versus remission). To avoid an ostomy, patients were willing to accept a >5% 10-year risk of dying from lymphoma or infection from medical therapy, regardless of medication efficacy. However, data on patients' stated choice indicated perceived equivalence between J-pouch surgery and incompletely effective medical therapy. Patient characteristics and disease history influenced patients' preferences regarding surgery versus medical therapy. Patients with UC are willing to accept relatively high risks of fatal complications from medical therapy to avoid a permanent ostomy and to achieve durable clinical remission. However, patients view J-pouch surgery, but not permanent ileostomy, as an acceptable therapy for refractory UC in which medical therapy is unable to induce a durable remission.

Fecal chromogranins and secretogranins are increased in patients with ulcerative colitis but are not associated with disease activity

BackgroundLittle is known of the importance of chromogranins (Cg) and secretogranins (Sg) in ulcerative colitis (UC). We therefore investigated fecal levels of CgA, CgB, SgII and SgIII, and their association with inflammatory activity, disease duration and medical therapy in UC. MethodsAnalyses of CgA, CgB, SgII, SgIII and calprotectin in stool samples from 41 UC patients and 29 healthy controls were performed. Two stool samples, during relapse and remission, respectively, were obtained from each UC patient. ResultsThe levels of fecal CgA and SgII were higher in UC patients with active disease as compared to healthy controls. CgB and SgII were positively correlated with disease duration, but none of the granins were positively correlated with calprotectin, Mayo score, CRP or serum concentrations of TNF in UC patients with active disease. Also UC patients in remission had higher levels of CgA, CgB, SgII, and SgIII as compared to healthy controls. However, levels of fecal CgA, CgB, SgII and SgIII were lower during active disease relative to remission. Moreover, fecal levels of CgA and SgII were higher in UC patients in remission treated with thiopurines than in thiopurine-naïve patients in remission. ConclusionFecal chromogranins and secretogranins are increased in UC but are not associated with disease activity, but seem to increase with duration of the disease. Thus, fecal granins might reflect structural changes associated with chronicity of disease, or medical therapy.

Treatment of Ulcerative Colitis in the Elderly: A Systematic Review

Ulcerative colitis (UC) is increasingly recognized as a disease affecting the elderly. Approximately 10%–30% of the UC population is over the age of 60 years. Additionally, younger patients with UC are aging and thus comprise a second group of elderly IBD patients. To date, there have been no clinical trials that have evaluated treatment efficacy of UC in the elderly population. The aim of our study was to conduct a systematic review of all randomized controlled trials (RCTs) addressing treatment outcome in UC; we also sought to identify the elderly population, defined as age 60 years or older, represented in these studies, to see if pooled data would lead to meaningful conclusions regarding treatment efficacy and safety profile in the elderly. A search of the MEDLINE database via PubMed and the EMBASE database via Scopus was performed to identify all RCTs evaluating medical therapy for UC in humans, published within the English language through September 2012. Studies were grouped into three categories: biological agent (BA) therapy; immunosuppressant (IS) therapy; and 5-aminosalicylic acid (5-ASA) therapy. To estimate the number of elderly patients in each study, mean age plus 1 and 2 standard deviations (SD) was calculated to find the closest approximation to age 60. Of 876 studies, 112 RCTs were included in the final analysis—20 studies for BA, 20 for IS, and 72 for 5-ASA agents. While nearly all studies reported either a mean or median age, only 38% additionally reported the SD and age range. The mean composite age was 39.2 years for the BA studies, 38.5 years for the IS studies, and 42.8 years for the 5-ASA studies, consistent with a young middle-aged patient. We estimated that no more than 16% of patients per study would have qualified as elderly, and in most cases a much smaller percentage (<8%). Additionally, there were no BA or IS RCTs that reported results by age subgroup analysis. Four studies in the 5-ASA group report age-specific analyses and showed no difference in treatment efficacy by age. None of the 112 RCTs reported age sub-analyses of safety, tolerability, adverse events, or withdrawal rates. There is insufficient evidence to evaluate efficacy of treatment and adverse events from treatment for UC in the elderly. With the rising number of elderly patients with UC, there is a need for more clinical trials that specifically address UC treatment in this unique population.

Exploring the ameliorative potential of probiotic Dahi containingLactobacillus acidophilusandBifidobacterium bifidumon dextran sodium sulphate induced colitis in mice

Conventional medical therapies for ulcerative colitis (UC) are still limited due to the adverse side effects like dose-dependent diarrhoea and insufficient potency to keep in remission for long-term periods. So, new alternatives that provide more effective and safe therapies for ulcerative colitis are constantly being sought. In the present study, probiotic LaBb Dahi was selected for investigation of its therapeutic effect on DSS-induced colitis model in mice. LaBb Dahi was prepared by co-culturing Dahi culture of Lactococci along with selected strain of Lactobacillus acidophilus LaVK2 and Bifidobacterium bifidum BbVK3 in buffalo milk. Four groups of mice (12 each) were fed for 17 d with buffalo milk (normal control), buffalo milk plus DSS (Colitis control), Dahi plus DSS, and LaBb Dahi plus DSS, respectively, with basal diet. The disease activity scores, weight loss, organ weight, colon length, myeloperoxidase (MPO) and β-glucoronidase activity was assessed, and the histopathological picture of the colon of mice was studied. All colitis control mice evidenced significant increase in MPO, β-glucoronidase activity and showed high disease activity scores along with histological damage to colonic tissue. Feeding with LaBb Dahi offered significant reduction in MPO activity, β-glucoronidase activity and improved disease activity scores. We found significant decline in length of colon, organ weight and body weight in colitis induced controls which were improved significantly by feeding LaBb Dahi. The present study suggests that LaBb Dahi can be used as a potential nutraceutical intervention to combat UC related changes and may offer effective adjunctive treatment for management of UC.

Drivers of Cost After Surgical and Medical Therapy for Chronic Ulcerative Colitis

We previously reported the costs associated with surgery for chronic ulcerative colitis in the Olmsted County population and found that direct medical costs after surgery were significantly reduced compared with before surgery. However, in that study, costs associated with chronic medical therapy for ulcerative colitis were not assessed in nonsurgical patients. To gain insight into the drivers of costs of treatment for chronic ulcerative colitis, we assessed direct costs after surgical and medical therapy in 120 patients in the Rochester Epidemiology Project database. A cohort of 60 patients who recovered from surgery for ulcerative colitis from 1988 to 2006 were 1:1 matched by age, sex, and referent year to medically managed patients. Direct health care costs were estimated from an institutional database, and observed cost differences over a 2-year period were calculated. Statistical significance was assessed by paired t tests and bootstrapping; mean costs are adjusted 2009 constant dollars. Two-year direct health care costs in the surgical and medical cohorts were $10,328 vs $6,586 (p = 0.19). In the surgical cohort, Brooke ileostomy patients were observed to have higher costs than patients with ileal pouches ([INCREMENT]$8187, p = 0.04), and after ileal pouch, pouchitis was associated with increased costs ([INCREMENT]$12,763, p < 0.01). In the medical cohort, disease extent ([INCREMENT]$6059, p = 0.04) but not disease severity was associated with increased costs. This study was limited by the relatively small population size and by its performance in a county with a tertiary referral center. Before the introduction of biologic therapies for ulcerative colitis, patients were observed to have similar health care costs after surgical and medical therapy. In medically treated patients, disease extent was associated with increased costs, whereas in surgically treated patients, permanent ileostomy and pouchitis were observed to be associated with increased costs.

Thrombosis, an Early Presentation and Extensive Spondylosis, a Late Complication of Inflammatory Bowel Disease

Inflammatory bowel disease(IBD) comprises two major disease entities, ulcerative colitis and Crohn's disease, that may be complicated by a variety of extra-intestinal manifestations. We reported a 55 years old male patient presented by leg thrombosis years before developing florid intestinal manifestations of IBD. After a detailed history taking and investigations, the patient proved to have ulcerative colitis with extensive spondylosis of the spine and had thrombocytosis. The condition of the patient improved on medical therapy for ulcerative colitis plus anti-platelet drug.