Outcomes Of 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.

P404 Monocyte distribution width differentiates bacterial gastroenteritis from Acute Severe Ulcerative Colitis in patients presenting with diarrhoea

Abstract Background Monocyte distribution width (MDW) is a haematological parameter that can be generated by newer generation blood analysers on routine full blood examination. It reflects the variation in the size of monocytes and is elevated in the setting of infection, however its utility in inflammatory disorders in unknown. We aimed to assess whether MDW can help differentiate bacterial gastroenteritis from Acute Severe Ulcerative Colitis (ASUC) among patients presenting to the Emergency Department (ED) with diarrhoea. We further aimed to assess whether MDW correlated with disease activity and clinical outcomes in ASUC. Methods We conducted a retrospective cohort study comprising three patient groups: (1) ASUC, (2) bacterial gastroenteritis and (3) a control group of patients without active inflammation. The control group consisted of outpatients with chronic hepatitis B in immune control phase with normal liver transaminases and suppressed viral load < 2000 IU/mL. Clinical outcomes, routine biomarkers and MDW were recorded. Results A total of 176 patients were identified (53 ASUC, 70 bacterial gastroenteritis and 53 controls). At time of ED presentation, patients with bacterial gastroenteritis had the highest MDW (median 23.6, IQR 20.7-25.8) compared to ASUC (19.0, IQR 17.9-21.2) and controls (16.8, IQR 15.9-18.0; P<0.001). On receiver operator characteristic curve analysis, MDW discriminated bacterial gastroenteritis from ASUC with an area under the curve (AUC) of 0.78 (95% CI 0.70-0.87, P<0.001). Using Youden’s index, a MDW threshold > 22.3 had 64.3% sensitivity, 84.6% specificity, 63.8% negative predictive value and 84.9% positive predictive value for bacterial gastroenteritis. Of the 53 patients with ASUC, 25 responded to intravenous hydrocortisone while 28 were steroid non-responders and required infliximab (IFX). 24 patients responded to IFX rescue, while the 4 IFX non-responders received tofacitinib sequential therapy. In ASUC, MDW correlated positively with established markers of disease activity including CRP (Spearman rank correlation, rho=0.54, P<0.001), platelet count (rho=0.36, P=0.009) and faecal calprotectin (rho=0.35, P=0.02). A lower MDW on the day of IFX administration appeared to predict IFX response (AUC 0.80, 95% CI 0.61-1.00, P=0.002). At follow-up (median 85 days), MDW was predictive of biochemical remission with a faecal calprotectin < 100 µg/g (AUC 0.80, 95% CI 0.64-0.95, P<0.001). Conclusion MDW is a novel biomarker that may help distinguish ASUC from bacterial gastroenteritis at time of ED presentation in patients with diarrhoea. In ASUC, MDW correlates with existing markers of activity and may help predict IFX response.

Sarcopenia assessed by computed tomography is associated with colectomy in patients with acute severe ulcerative colitis.

Altered body composition is an important characteristic of malnutrition that may better reflect the clinical course. This study aimed to evaluate the prognostic role of sarcopenia by computed tomography (CT) on colectomy in acute severe ulcerative colitis (ASUC) during index hospitalization and follow-up. 254 ASUC patients undergoing CT scans at admission were retrospectively included. Sarcopenia was assessed by the skeletal muscle index (SMI) with CT scans at L3, and patients with an SMI below the lowest sex-specific quartile were diagnosed with sarcopenia. Body mass index (BMI) < 18.5 kg/m2 was defined as clinical malnutrition. Univariate and multivariate analyses were performed to determine the association between sarcopenia and colectomy. The prevalence of sarcopenia in ASUC was 50.0%, and malnutrition was 25.2%. Among sarcopenic patients, 36.2% was malnutrition, 51.2% had normal BMI, 11.8% was overweight, and 0.8% was obese. During index hospitalization, 66.9% patients needed rescue therapy with 52.4% received medical rescue therapy and 14.6% received colectomy. During follow-up, 33.2% patients needed colectomy. Significantly more sarcopenic patients required colectomy (22.0% vs 7.1%, p = 0.001) and rescue therapy (81.9% vs 52.0%, p < 0.001) during index hospitalization and colectomy during follow-up (44.4% vs 23.7%, p = 0.001) than non-sarcopenic patients. However, BMI < 18.5 kg/m2 was not related to the clinical course. In multivariate analyses, sarcopenia remained an independent risk factor for rescue therapy and colectomy during index hospitalization and colectomy during follow-up. Sarcopenia rather than BMI was associated with clinical outcomes in ASUC and played an important role in predicting the need for colectomy.

P302 Serum IL-6 is associated with treatment refractoriness in acute severe ulcerative colitis

Abstract Background Response to therapy in acute severe ulcerative colitis (ASUC) is highly variable ranging from steroid response to salvage therapy failure and emergency colectomy. Biomarkers that accurately predict outcomes in ASUC early in the admission may help improve its management. We aimed to ascertain whether peripheral serum cytokine levels on admission correlate with refractoriness to medical therapy. Methods Peripheral blood was collected from 34 subjects, including 29 patients with ASUC on admission (baseline) and 5 healthy controls. All patients with ASUC received intravenous steroids, with those refractory to steroids going on to receive infliximab (IFX) salvage. Eight cytokines were measured at baseline using a multiplexed cytokine assay (Bio-Rad). Clinical response to steroids and/or to the first IFX dose was assessed and used to classify patients based on increasing order of disease refractoriness (steroid-responders, IFX-responders and IFX non-responders). These groups were then evaluated to check for correlations with baseline cytokine levels. Results Our cohort consisted of steroid responders (n=9), IFX responders (n=12) and IFX non-responders (n=8). Median serum IL-6 level was 1.6 pg/mL (IQR:1.6-2.1) in healthy controls compared to 2.7 pg/mL (IQR:1.4-6.3) in ASUC (p=0.3). In patients with ASUC, there was a positive correlation between IL-6 and treatment refractoriness (Spearman’s correlation [rs]=0.56, p=0.002). Compared with steroid responders (1.36 pg/mL), serum IL-6 was significantly higher in both IFX responders and IFX non-responders (3.44 and 5.50 pg/mL, p=0.02 and p=0.009 respectively) (Fig 1). Patients with ASUC had higher serum IL-8 compared to healthy controls (17.8 vs 6.9 pg/mL, p=0.005). There was no correlation between IL-8 levels and ASUC treatment refractoriness (rs=0.22, p=0.3). Similarly, there was no difference in IL-8 levels in ASUC patients when classified by treatment response (Kruskal Wallis, p=0.5). Serum TNF level did not differ between healthy controls and patients with ASUC (19.5 and 22.2pg/mL, p=0.5). TNF levels did not correlate with treatment refractoriness in ASUC (rs=-0.06, p=0.75) and there were no differences between the ASUC response groups (p=0.6). Levels of GM-CSF, IFN-g, IL-2, IL-4 and IL-10 were predominantly below the detection limit of each assay. Conclusion In this ASUC cohort, serum IL-6 level on admission correlated with treatment refractoriness and may help identify patients at higher risk of requiring salvage therapy as well as those at higher risk of failing IFX. Further studies are needed to elucidate the function of IL-6 in ASUC and whether it may represent a potential predictor of outcomes in ASUC.

Adjuvant use of combination of antibiotics in acute severe ulcerative colitis: A placebo controlled randomized trial

ABSTRACT Objectives Evaluation of a combination of antibiotics as an adjuvant therapy in acute severe ulcerative colitis (ASUC). Methods Patients with ASUC were randomized to either infusions of placebo or intravenous ceftriaxone and metronidazole in addition to standard care. Primary outcome was response on day three according to Oxford’s criteria. Secondary outcome measures included changes in partial Mayo score, CRP levels, fecal calprotectin (day three), and need for second-line therapy, hospital stay, and mortality (day 28). Results Fifty patients (25 in each group, median age: 33 years, 23 males) were included. The number of patients with fulminant disease in the antibiotic group were 16 (64%) as compared to 7 (28%) in the standard of care group. Complete response on day three was attained by 7 (28%) in the antibiotic and 6 (24%) standard of care group (p = 1.00). Three patients from the antibiotic group underwent colectomy and three received intravenous cyclosporine whereas four patients in the standard of care group received cyclosporine (p = 0.725). There was no significant difference in change in CRP, Partial Mayo score, and fecal calprotectin between the two groups on day three. Conclusion Combination of intravenous ceftriaxone and metronidazole did not improve outcomes in ASUC. Acronym: AAASUC trial Registration Number: CTRI/2019/03/018196 and NCT03794765

P070 Outcomes of Acute Severe Ulcerative Colitis in Older Adults.

BACKGROUND: Approximately 40% of patients with acute severe ulcerative colitis (ASUC) do not respond to steroids. There is paucity of data on the outcomes of ASUC in the older adults (≥60 years of age). The primary objective of our study was to assess steroid failure rate. The secondary outcomes assessed were need for colectomy during same admission, at 3 and 12 months; mortality during admission for ASUC, at 3 months and 12 months. METHODS: All admissions for ASUC (fulfilling Truelove and Witts Criteria) between January 1, 2015 and July 31, 2020 at Gold Coast University Hospital and from January 1, 2018 to July 31, 2020 at Logan Hospital were analysed. Review of electronic medical records was performed and clinical, endoscopic, laboratory data were collected. Steroid failure was defined as need for rescue therapy (medical or surgical). For comparisons of proportions, we used Pearson's chi-square analyses or Fisher's exact tests. Non-parametric data were compared using Kruskal-Wallis test. Parametric data were compared using paired t-test. To test for independent predictive factors a logistic regression model was constructed with steroid failure as the dependent variable. RESULTS: We analyzed 194 episodes (153 patients) of ASUC, of which 41 episodes (32 patients) were in patients who were ≥ 60 years of age at the time of ASUC event. 29 episodes (23 patients) in whom UC was diagnosed ≥60 years of age. Fourteen (43.75%) female, median disease duration 2 years (0–6), median Charlson Comorbidity Index 3 (2–4). Fourteen (34.1%) episodes occurred in patients on biological therapy (6 on anti-TNF antagonists, 8 on Vedolizumab), 15 (36.6%) episodes were on oral corticosteroids at admission. Eighteen (43.9%) required rescue therapy (2 episodes underwent colectomy, 16 episodes received medical rescue therapy (11 infliximab, 5 cyclosporine); 7 patients received IFX 5 mg/kg, 4 patients received IFX 10 mg/kg. In adults ≥60 years, 5 (12.2%) episodes had a colectomy during the admission for ASUC (vs 7.8% in adults < P 0.0001) when compared to patients < 60 years of age. There was no mortality in patients < 60 years of age. On univariate analysis of admission variables. albumin (OR 0.83, P 0.015, CI 0.70–0.96), CRP (OR 1.01, P 0.033, CI 1.00–1.02), UCEIS score (OR 3.68, P 0.016, CI 1.27–10.60) were significant for predicting steroid failure. On multivariate regression analysis, UCEIS score and albumin remained significant. CONCLUSION: In patients who are ≥ 60 years of age, steroid failure rate, the need for colectomy during the same admission and colectomy at 12 months is similar to a population.

The Importance of Sarcopenia as a Prognostic Marker for Clinical Course and Postoperative Outcomes in Acute Severe Ulcerative Colitis Patients

Background: Acute severe ulcerative colitis (ASUC) is a life-threatening condition, which needs timely referral for first-line and second-line therapy. Although various clinical parameters for predicting response to intravenous steroid (IVS), rescue medical therapy, or colectomy and for evaluating postoperative outcomes already exist, there is few data concerning the role of sarcopenia in ASUC. The relationship between sarcopenia and clinical course in ASUC was evaluated in this study. Methods: This cohort study included ASUC patients with abdominal CT scan. Quantification of body composition was assessed. Multivariable regression was performed to find out a practical predictive index for clinical course and colectomy of ASUC. Findings: Of 233 included patients, 151 showed nil response to IVS therapy, among whom 32 received surgery without rescue medical therapy. 50 patients suffered colectomy after medical rescue therapy failure during one-year follow-up. Of 82 surgical patients, 42 recovered eventfully. Multivariable regression analysis showed sarcopenia (OR=2.962; 95% CI, 1.532-5.726; p=0.001) remained an independent risk factor for IVS failure, subcutaneous fat areas (OR=0.985; 95% CI, 0.970-1.000; p=0.046) was an independent predictor for colectomy during one year after second-line medical failure, and sarcopenia (OR, 4.157; 95% CI, 1.364-12.667; p=0.012) remained an independent risk factor for postoperative complications. During follow-up, patients with colectomy after first-line medical had higher health-related quality of life and sarcopenic patients suffered the pouchitis more frequently. Interpretation: The sarcopenia was superior to other common indicators in predicting clinical course and postoperative outcomes in ASUC. Funding Statement: This work was supported by National Natural Science Foundation of China (grant number 81800474). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: This cohort study was approved by the Ethics Committee of Medical School of Zhejiang University, China.

Has infliximab influenced the course and prognosis of acute severe ulcerative colitis?

Ulcerative colitis (UC) still has no definitive cure since its etiology remains unclear. In recent years, considerable progress has been made with regard to our knowledge of the pathogenesis of UC. Advances in biotechnology have led to the development of biologic therapies which selectively target single key mediators or receptors involved in the pathogenesis of the disease – ie, tumor necrosis factor (TNF)-α, integrin, interleukins 12/23. Biologic therapies caused a revolution in the treatment of UC, providing specific options for patients refractory to conventional treatment. In recent years, antibodies anti-TNFα and anti-integrin have shown efficacy in improving the course and prognosis of ambulatory patients with moderate-to-severe UC. Nevertheless, whether biologics have brought so many benefits also for hospitalized patients with acute severe UC is still debated. Acute severe UC is a potentially life-threatening condition that affects up to 25% of patients during the course of their disease. It requires hospital admission due to the risk of complications and death, and it can necessitate urgent colectomy. Major adverse outcomes of acute severe UC are mortality and colectomy. The aim of this systematic review of the literature was to analyze the impact of biologics, in particular infliximab, on the course and prognosis of acute severe UC. Mortality and colectomy rates were considered as outcome measures.

Risk stratifying in real life.

Risk stratifying in real life.

Induction infliximab levels among patients with acute severe ulcerative colitis compared with patients with moderately severe ulcerative colitis.

Infliximab is effective as salvage therapy for patients with steroid refractory acute severe ulcerative colitis (UC). Although current data suggest that the pharmacokinetics of infliximab are influenced by inflammatory burden in patients with acute severe UC, data comparing infliximab trough levels in patients with acute severe UC vs. moderately severe UC are scarce. To compare infliximab trough and anti-infliximab antibody levels at a standard fixed time-point during induction between patients with acute severe and moderately severe UC. A multi-centre retrospective study comparing infliximab drug and antibody levels 14 days after the first infusion in hospitalised acute severe UC versus out-patients with moderately severe UC was performed. Sixteen acute severe UC patients, hospitalised between 2010-2015 and refractory to intravenous corticosteroids, were treated with infliximab 5 mg/kg salvage therapy. They were compared to 16 moderately severe UC out-patient controls. Mean infliximab trough levels at day 14 were significantly lower in patients with acute severe UC compared to moderately severe UC (7.15 ± 5.3 vs. 14.4 ± 11.2 μg/mL, P = 0.007). Seven patients (three acute severe and four moderate severe UC) were primary nonresponders to infliximab induction therapy. Infliximab level at day 14 did not differ between responders and nonresponders (9.8 ± 9 vs. 12.1 ± 10.6 μg/mL, respectively, P = N.S.). However, week 2 median antibody-to-infliximab levels were numerically higher among primary nonresponders (3.4 ± 5.7 vs. 1.2 ± 4 μg/mL-eq, respectively, P = 0.06). Infliximab trough levels at day 14 were lower in patients with acute severe UC compared to moderately severe UC, possibly due to a higher inflammatory burden and/or increased drug clearance. However, drug levels at day 14 were not lower among nonresponders compared with responders. Controlled trials are warranted to examine whether an a-priori-intensified infliximab induction protocol will lead to an improved outcome in acute severe UC.

Anxiety and Psychological Stress in Acute Severe Ulcerative Colitis: Prevalence and Effect on Outcome

Introduction There is increasing evidence that psychological stress and associated mood disorders are linked with, and adversely affect the course of IBD. The authors hypothesise that: (1) anxiety and stress are more common in acute severe ulcerative colitis (ASUC) than in patients with inactive UC; (2) anxiety and stress are more common in patients presenting for the first time with UC; (3) anxiety and stress worsen outcome in ASUC. Methods 39 ASUC patients (aged 28 (18–74) years (median (range)); disease duration 10 (0–240) months), requiring hospital admission and intravenous hydrocortisone with a Baron9s sigmoidoscopic score ≥2, completed questionnaires to assess anxiety (Hospital Anxiety and Depression Score (HADS-A)) and stress levels (Perceived Stress Questionnaire: Recent, R-PSQ, General, G PSQ). Outcomes were assessed, using the Travis criteria (day 3) and colectomy rates at day 70, in relation to upper and lower tertiles of the anxiety and stress scores. In addition, the psychometric scores of the ASUC patients were compared to those of 27 outpatients with inactive UC. Results Patients with ASUC had higher stress levels (R-PSQ Index 0.52 (0.03) (mean (SEM)), G-PSQ 0.46 (0.03)) than in patients with inactive UC (0.35 (0.03), p=0.001, 0.39 (0.02), p=0.046, respectively) but there was no difference in anxiety scores (HADS-A 9.6 (0.8), 8.4 (0.7), p=0.9, respectively). However, in patients with ASUC, there was a positive correlation between stress and anxiety scores (R-PSQ, r2=0.27, p=0.0008; G-PSQ, r2=0.14, p=0.02)). Although stress scores were similar, anxiety levels were higher in the 11 newly presenting ASUC patients (12 (1.4)) than in those previously diagnosed (8.6 (0.9), p=0.049). There was no difference in those responding to intravenous hydrocortisone (by Travis criteria) or in day 70 colectomy rates between patients who were highly (upper tertile) anxious (Travis response 8/13, colectomy rate 2/13) or highly (upper tertile) stressed (R-PSQ: Travis response 8/12, colectomy rate 6/13; G-PSQ Travis response 5/13, colectomy rate 4/13) compared to those less (lower tertile) anxious (5/13, 3/13, respectively) or stressed (lower tertile) (R-PSQ, 5/13, 1/13; G-PSQ 5/12, 1/13, respectively). Conclusion Perceived stress levels are greater in patients with ASUC than in those in remission and anxiety scores are highest in patients newly presenting with UC, but neither stress nor anxiety influenced disease outcome.