Refractory Acute Severe Ulcerative Colitis Research Articles

Inpatient Infliximab Biosimilar Cost-Savings: Cost Analysis of Inpatient Treatment with Originator Infliximab (Remicade™) versus Biosimilar Infliximab (Renflexis™) for Acute Severe Ulcerative Colitis

Introduction: Infliximab (IFX) is a standard, inpatient salvage therapy for the treatment of refractory acute severe ulcerative colitis (ASUC). Remicade™ is the originator IFX. Its biosimilar Renflexis™ offers a reduced cost structure. We performed a cost-minimization analysis to compare costs with Remicade™ and Renflexis™ for the inpatient treatment of ASUC. Methods: Retrospective clinical and financial data were obtained from 34 inpatients with refractory ASUC who received Renflexis™ (n = 17) or Remicade™ (n = 17) between 2019 and 2021. Clinical data included admission and discharge laboratory values. Financial data included a decision support drug cost (DSDC), constituting the total cost associated with inpatient IFX administration, and total inpatient cost of care. The following equation generated a ratio (rDSDC) representing the percentage of drug cost (or DSDC) of the total inpatient cost of care, after controlling for IFX dose and length of stay: [DSDC of IFX/Number of Units of IFX] ÷ [Total Inpatient Cost of Care/Length of Stay in Days]. Median and non-parametric Wilcoxon ranked sum test were used for analyzing patient demographics, clinical, and financial data. Results: No differences were found in baseline or discharge clinical parameters. The median unadjusted ratio of DSDC to total inpatient cost of care was 0.387 versus 0.241 in the Remicade™ versus Renflexis™ groups (p = 0.0025), respectively, representing an absolute difference of ∼14%. Median adjusted rDSDC were 0.04 versus 0.024 in the Remicade™ versus Renflexis™ groups, respectively, representing a relative cost reduction of ∼40% (p = 0.0001). Discussion: The unadjusted absolute cost reduction and adjusted relative cost reduction were, respectively, 14% and 40% in the Renflexis™ group as compared to Remicade™, when treating inpatient ASUC. Our calculation included median DSDC as a percentage of the total inpatient cost of care, controlling for IFX dose and length of stay. This reduced cost structure promotes use of Renflexis™ for ASUC inpatients and may reduce costs systemically.

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.

UPADACITINIB AS SECOND- AND THIRD-LINE SALVAGE THERAPY FOR REFRACTORY ACUTE SEVERE ULCERATIVE COLITIS

Abstract INTRODUCTION Intravenous (IV) corticosteroids (CS) remain first line therapy for acute severe ulcerative colitis (ASUC). Up to 40% are CS refractory. Prior biologic exposure, colonic drug loss and systemic toxicities limit their utility. Colectomy rates remain up to 30% in CS refractory cases emphasizing the need for expanding alternative strategies. We report our experience of upadacitinib (UPA) as 2nd and 3rd line salvage in refractory ASUC. METHODS ASUC was defined by Truelove and Witts’ criteria. Travis index was used to assess 3-day response to inpatient (IP) therapies. IP therapeutic non-response was defined as ≥ 8 bowel movements (BM)/day or > 2 BM and CRP > 45 mg/L. IP response was defined as ≤ 4 BM and CRP < 45 mg/L. Primary outcome include response to IP UPA salvage at day 3 and colectomy by week (WK) 16. Patients (pts) undergoing colectomy were followed until time to event. Secondary outcomes include post-discharge clinical and biochemical remission, clinical response and rate of adverse events at WK 8/16. Clinical remission/response was defined by STRIDE-2 guidelines using partial mayo (PM). Biochemical remission was defined as fecal calprotectin (FC) <250 ug/g or CRP <5 mg/L. No cardiovascular, thromboembolic or non-HSV infections were seen. RESULTS Four ASUC pts failing IV CS required inpatient UPA salvage (Table 1). At baseline, all pts had severe pancolonic endoscopic disease (median total mayo 11, median PM 9). Median exposure to prior advanced therapies was 4. Baseline median FC was 3000 ug/g and CRP 167 mg/dL. Pt #1, #2 received UPA as 2nd line salvage due to prior IFX failure (Table 2). Pts #3, #4 received UPA as 3rd line salvage due to IFX failure at index admission (IA). One received UPA 45 mg QD (pt #1) and three received 30 mg BID (pts #2-4). All pts achieved IP response to UPA. No pts needed colectomy at IA. Overall median length of hospital stay was 14 days. Median time to UPA response was 2.5 days. Discharge time post-UPA was 3.5 days. At WK 8, pt #1 attained response with resolution of rectal bleeding (RB), BM (-85%), CRP (-91%), FC (-82%), and PM 3 (Table 3-4). At WK 16, pt #1 met criteria for clinical and biochemical remission with PM 1, normal FC (-95%) and CRP (-98%). Pt #1,#3 achieved complete steroid taper and avoided colectomy over 16 WK. Pt #2 failed CS taper and had colectomy on day 33. Pt #3 achieved clinical and biochemical remission with PM 1 and CRP 5 mg/dL (-94%) at WK 8. At WK 16, pt #3 sustained CS free clinical and biochemical remission with normalized BM (-93%), FC (-92%), CRP (-98%) and sustained resolution of RB. Assessment of pt #4 was limited to IP UPA response pending follow up. Outcomes were similar in pts receiving UPA as 2nd and 3rd line salvage. CONCLUSION We report efficacy and safety of UPA as 2nd and 3rd line salvage for ASUC thus expanding the armamentarium for medical salvage therapy. Table 1 Baseline Disease Characteristics Table 2 Patient Specific Inpatient Therapy Table 3 Comparison of Disease Activity Parameters at Baseline, Discharge, 8 Weeks and 16 Weeks Table 4 Percentage Difference of Disease Activity Parameters at Discharge, 8 Weeks and 16 Weeks in Comparison to Baseline

P223 Early prediction and objective criteria to define failure of rescue medical therapy in acute severe ulcerative colitis

Abstract Background Medical rescue therapy (MRT) is effective in intravenous corticosteroid refractory acute severe ulcerative colitis (ASUC). We recently described the ADMIT-ASC score to identify patients on admission at high risk of steroid failure. In this setting, our primary objective in this analysis is now to identify parameters at admission which could identify non-response to MRT, following corticosteroid failure. Co-primary objective is to develop and validate a model to identify non-responders to MRT. Methods Two cohorts were studied, for discovery and validation. Retrospective analysis of 66 adult ASUC admissions receiving MRT between 2015-19 at Gold Coast University Hospital and Logan Hospital was first performed. Clinical, endoscopic and laboratory data were collected. Non-response was defined as undergoing colectomy during the index admission. Univariable and multivariable logistic regression were employed to identify predictors of non-response. A predictive model was developed based on thresholds obtained from ROC curves. The predictive model was validated in 99 patients admitted to Gold Coast University Hospital and Sunshine Coast University Hospital between 2020-23. Results In the 2015-19 cohort, out of 66 episodes who received MRT, 11 episodes (16.7%) underwent colectomy during the same admission. UCEIS at admission was the strongest predictor of non-response to MRT [OR 3.03 (95%CI 1.47-6.22), p 0.033), AUROC 0.7552 (95%CI 0.6271 – 0.8832]. UCEIS score ≥6 had sensitivity 100%, specificity 41.7%, PPV 26.3%, NPV 100%, to predict non-response to MRT. CRP on day 3 after commencing rescue therapy (CRP Day R+3) was also a predictor for non-response to MRT (OR 1.02 (95%CI 1.00-1.05), p 0.015). A score comprising 2 points involving UCEIS ≥ 6 and CRP value of ≥ 22 mg/L on day R +3 was developed (1 point each). Score of 2 points had accuracy 79.6%, specificity 75%, sensitivity 100%, PPV 47.4%, NPV 100%, AUROC 0.8750 (95%CI 0.8070-0.9429) for non-response to MRT. In the validation cohort, 6 (6.1%) patients underwent colectomy during the same admission after failing MRT. On implementing the score, a score of 2 points had accuracy 86.7%, specificity 88.1%, sensitivity 66.7%, PPV 28.6%, NPV 97.4%, AUROC 0.8095 (95%CI 0.6423-0.9768) for predicting non-response to MRT. Conclusion UCEIS score at admission and CRP on day 3 after commencing MRT are predictors of non-response to MRT. We have developed and validated a model to identify non-response to medical rescue therapy, and objective criteria to mandate surgical intervention.

S3184 Tofacitinib-Induced Remission in a Case of Infliximab and Steroid Refractory Acute Severe Ulcerative Colitis

S3184 Tofacitinib-Induced Remission in a Case of Infliximab and Steroid Refractory Acute Severe Ulcerative Colitis

S3207 Induction of Remission in TNF-Alpha Inhibitor Refractory Acute Severe Ulcerative Colitis With Upadacitinib: A Case Report

S3207 Induction of Remission in TNF-Alpha Inhibitor Refractory Acute Severe Ulcerative Colitis With Upadacitinib: A Case Report

WITHDRAWN: Non-Anti-TNF Biologics as Salvage Therapy for Refractory Acute Severe Ulcerative Colitis, A Systematic Review

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P621 Combination treatment of biologics with immunomodulator increases risk of infection after discharge in biologics naive steroid refractory acute severe ulcerative colitis patient: A KASID multicenter study

Abstract Background Biologics such as infliximab is the main treatment for steroid refractory acute severe ulcerative colitis (ASUC), However, there are only a few studies on the effectiveness and safety of biologics in steroid refractory ASUC. In this study, we evaluated the effectiveness and safety of biologics as a rescue therapy for biologics naïve steroid refractory ASUC patient in Korea. Methods We retrospectively included patients who were hospitalized at seven tertiary medical centers for ASUC management between January 2015 to December 2020, and data on the demographic and clinical variables, disease activity, treatment method, treatment response, adverse event, readmission due to any reasons were checked Results A total of 230 ASUC patients were included, of which 220 were biologic naïve patient. The response rate of steroid in these patients was 74%, and infliximab was administered as rescue therapy to 53 patients who failed initial steroid treatment. The response rate to infliximab as rescue therapy was 96%, and 2 patients who did not respond received colectomy. One of the two patients who underwent colectomy died of sepsis. There was no infliximab-related adverse event during hospitalization. Although infliximab itself was not a factor associated with infection after discharge (10% vs. 16%, p=0.355), combination therapy with thiopurine was a risk factor for infection after discharge. (Odd ratio 7.302, 95% CI 2.101-25.372, p=0.002). A total of 12 infections occurred in patients treated with infliximab after discharge (3 pneumonia, 1 skin infection, 3 cytomegalovirus colitis, 4 Clostridium difficile infection) and were associated with readmission. (40.1% vs. 75%, p=0.031) Conclusion As a rescue therapy in biologics naive steroid refractory ASUC, infliximab showed a 96% therapeutic response. Although infliximab itself did not increase the risk of infection after discharge, the combination with thiopurine increased the risk of infection after discharge

P472 Cyclosporine versus infliximab in patients with Acute Severe Ulcerative Colitis: A single-centre retrospective study

Abstract Background In steroid refractory acute severe ulcerative colitis (ASUC), cyclosporine or infliximab are potential rescue treatments to avoid colectomy. Our objective is to assess the short-term and long-term efficacy and safety of cyclosporine versus infliximab as rescue agents. Methods We performed a retrospective analysis of 121 patients admitted with ASUC to a single gastroenterology centre during 2010-2020. ASUC was defined by the Truelove & Witts criteria. Primary outcome was short-term colectomy-free rate, secondary outcomes were severe adverse events, re-hospitalization or need of treatment with steroids within 2 years due to flare ups and colectomy rate at 2-year follow-up. Results 119 patients initially received intravenous corticosteroids, while 2 patients underwent emergency colectomy on the first day. Sixty-four (53%) were females, median age of all patients was 33 (IQR 27-49) years. 66 (55%) patients responded to intravenous corticosteroids (IVS), while 53 (45%) failed to respond to steroid therapy: 45 (37%) patients received second-line rescue therapy (29 with cyclosporine, 16 with infliximab). Evaluating the short-term efficacy of treatment there was no significant difference between cyclosporine and infliximab: during admission colectomy was performed in 10.3% vs. 12.5% of patients, respectively (p=0.826). In terms of long-term outcomes, the colectomy rate was higher in the infliximab group at 2-year follow-up, although the difference did not reach statistical significance (10.3% vs. 31.2%, p=0.079). The need for oral steroids during follow-up was comparable in both groups (38,5% vs. 50%, p=0.481). Comparing patients who did not undergo colectomy, patients in the infliximab group were more often re-hospitalized due to the need for IVS at 2-year follow-up (7.7% vs. 50%, p=0.002). No severe side effects due to infliximab and cyclosporine were observed. Conclusion In the treatment of steroid refractory ASUC infliximab and cyclosporine were equally effective in short-term period and there was no difference in safety, however cyclosporine treated patients trended to have better long-term outcomes, with significantly rarer re-hospitalization. Additional analysis is needed for other factors that may have contributed to differences in long-term outcomes between the cyclosporine and infliximab groups.

S990 Cost Analysis of Inpatient Originator Infliximab (Remicade) vs Biosimilar Infliximab (Renflexis) for Acute Severe Ulcerative Colitis: A Cost Minimization Study

Introduction: Infliximab (IFX) is a standard, inpatient salvage therapy for treatment of refractory acute severe ulcerative colitis (ASUC). Inpatient IFX, as the originator Remicade, significantly increases colectomy-free survival in this population. The biosimilar Renflexis offers reduced cost as compared to Remicade. We performed a cost-minimization analysis to compare costs with Remicade and Renflexis for inpatient treatment of ASUC. Methods: Retrospective clinical and financial data was obtained from 34 inpatients with refractory ASUC who had received treatment with Renflexis (17) or Remicade (17) between 2019-2021. Clinical data included admission and discharge serum albumin (alb), hemoglobin (Hgb), C-reactive protein (CRP), and colectomy rate within 30 days of treatment (CR-30). Financial data included a decision support drug cost (DSDC), depicting the total cost associated with inpatient infliximab administration, and total inpatient care cost, depicting the full cost of the inpatient admission. The following equation generated a ratio (rDSDC) which represents the percentage of how much the DSDC accounts for the total inpatient care cost, after controlling for dose of infliximab and length of stay. [DSDC of IFX/Number of Units of IFX] ÷ [Total Inpatient Cost of Care/Length of Stay in Days] Mean and unpaired T-test (parametric test) were used for clinical data analysis. Median and non-parametric test called Wilcoxon ranked sum test were used for financial data analysis. (Figure) Results: No differences were found in baseline or discharge clinical parameters including baseline CRP (P=0.64), alb (P=0.1294), Hgb (P=0.5051), discharge CRP (P=0.1244), alb (P=0.8728), Hgb (P=0.4875), or CR-30 (23.53% vs. 29.41%, p=0.6975) (Table). Median rDSDC was 0.387 vs. 0.241 in the Remicade vs. Renflexis groups, respectively (Figure, p = 0.0025) representing a difference of ∼14%. Conclusion: A 14% reduction in cost attributed to DSDC was found using Renflexis, as compared to Remicade, treating inpatient ASUC. Our calculation included median decision support drug cost as a percentage of the total inpatient care cost, controlling for dose of infliximab and length of stay. Such a reduced cost structure promotes use of Renflexis for ASUC inpatients, which may result in improved utilization, improved health outcomes, and reduced costs for patients and hospitals. Further studies may confirm non-inferiority and demonstrate cost-effectiveness.Figure 1 Table 1. - Remicade (n=17) Renflexis (n=17) P- Value Admission C-reactive protein 117.73 mg/L 103.98 mg/L 0.6400 Albumin 2.74 g/dL 2.45 g/dL 0.1294 Hgb 11.34 g/dL 10.82 g/dL 0.5051 Discharge C-reactive protein 17.18 mg/L 30.99 mg/L 0.1244 Albumin 2.36 g/dL 2.4 g/dL 0.8728 Hgb 10.11 g/dL 9.71 g/dL 0.4875 Colectomy rate within 30 days of Treatment 23.53% (n=4) 29.41% (n=5) 0.6975 Median ratio of decision support drug cost to total inpatient cost of care after accounting for number of units of IFX administered and length of inpatient stay in days 0.387 0.241 0.0025

Cyclosporine Therapy as a Rescue Treatment in Steroid Refractory Acute Severe Ulcerative Colitis: A Real Life Data From a Tertiary Center.

Cyclosporine is a rescue treatment alternative to avoid colectomy in corticosteroid refractory acute severe ulcerative colitis. In this study, we aimed to evaluate the long-term efficacy and safety of cyclosporine therapy in acute severe ulcerative colitis patients. Acute severe ulcerative colitis (basal Lichtiger score > 10) patients who did not respond to 40 mg intravenous methylpredniso- lone therapy after 3-5 days were included in the study. The presence of clinical response and remission was assessed at 1st week, 1st, 6th, and 12th month according to the Lichtiger index. In this study, 40 patients, whose steroid refractory acute severe ulcerative colitis and basal Lichtiger score > 10 points were enrolled. The median disease duration was 49.3 months (2-204). All patients received cyclosporine for 132 ± 78 days (7-270). Clinical response was obtained on seventh day in 82.5%. The clinical response rates of the first and sixth months were 72.5% and 62.5%, respectively. A total of 17/40 (42.5%) patients underwent colectomy within 1 year. In the patients who underwent colectomy, the basal LS (14.2 ± 1.9 vs 12.3 ± 1.7) (P = .002) was higher and the basal hemoglobin value (11.8 ± 2.3 vs 10.1 ± 1.5) (P = .037) was lower than those who did not undergo colectomy. Our findings suggest that cyclosporine treatment may be successfully and safely used in steroid refractory acute severe ulcerative colitis patients. Cyclosporine is a drug that has recently started to come up again with the introduction of new maintenance treatments. Especially in patients who develop a loss of response to infliximab therapy, or where infliximab therapy is contraindicated, or who have azathioprine intolerance, or are unresponsive.

Surgical Management of Medical Refractory Acute Severe Ulcerative Colitis in Immune Thrombocytopenic Purpura: Killing Two Birds With One Stone.

Surgical Management of Medical Refractory Acute Severe Ulcerative Colitis in Immune Thrombocytopenic Purpura: Killing Two Birds With One Stone.

P333 Endoscopic severity and CRP predict failure of medical rescue therapy in patients with acute severe ulcerative colitis

Abstract Background The efficacy of Infliximab and Cyclosporin A as medical rescue therapy in patients with corticosteroid refractory acute severe ulcerative colitis (ASUC) is well established. We aimed to identify predictors of failure of medical rescue therapy and colectomy during the same admission in this population. Methods Patients hospitalized with ASUC who received infliximab or cyclosporin A after failing intravenous corticosteroid therapy between 1st January 2013 to 31stJuly, 2020 at two Australian tertiary IBD centres were retrospectively analysed. Patients who underwent colectomy during the same admission after medical rescue therapy were defined as non-responders. Logistic regression analysis was performed to identify predictors of colectomy during same admission. Results 226 episodes of ASUC [110 (48.7%) female, median disease duration 2 years] were analysed. 104 (46%) episodes required rescue therapy [94 episodes received medical rescue (16 cyclosporine/78 Infliximab) and 10 underwent direct colectomy]. In patients receiving medical rescue therapy, 16 (17%) underwent colectomy during same admission and 28 (29.8%) underwent colectomy by 12 months. On multivariable analysis, UCEIS score at admission [Coef 0.100 (0.02-0.17), p 0.011] and CRP on Day 3 post-rescue therapy [Coef 0.004 (0.0007-0.007), p 0.018] were significant for predicting colectomy during the same admission. A score with 1 point for each variable (UCEIS score ≥ 7 and CRP value of ≥ 22 mg/L on day 3 post medical rescue therapy) was developed. A score of 2 points had sensitivity 57%, specificity 97%, PPV 80%, NPV 91%, accuracy 89% for predicting colectomy during the same admission and sensitivity 33%, specificity 94%, PPV 80%, NPV 67%, accuracy 69% for predicting colectomy at 12 months. Conclusion UCEIS and CRP on day 3 after rescue therapy are predictors of non-response to medical rescue therapy and need for colectomy during the admission for the ASUC episode. Combination of UCEIS ≥ 7 and CRP ≥ 22mg/L on day 3 post medical rescue therapy has a PPV of 80% for colectomy during same admission and at 12 months. The score can be used to make decisions about colectomy or further medical rescue therapy.

P452 Oral ciclosporin is a convenient, effective and safe rescue therapy in steroid refractory Acute Severe Ulcerative Colitis: A single tertiary centre experience

Abstract Background Parenteral ciclosporin (CsA) is an effective rescue therapy for acute severe ulcerative colitis (ASUC) and has similar efficacy to infliximab (IFX). Although CsA is cheaper and can facilitate bridging to any IBD therapy, including newer biologics, its use is limited by variable pharmacokinetics and possibility of significant systemic toxicity particularly associated with the intravenous preparation. Despite favourable pharmacokinetics and bioavailability, the use of lipid-emulsified oral CsA in steroid-refractory ASUC is undefined. Methods All patients who received oral CsA (Neoral®) rescue therapy for ASUC at Addenbrooke’s Hospital, Cambridge, UK from Nov 2014 to May 2020 were identified from electronic healthcare records. Baseline data and outcomes were extracted and compared to patients who received IFX rescue therapy. Statistical significance was assessed using non-parametric tests. Survival estimates were computed using the Kaplan-Meier method. Results A total of 37 patients received oral CsA for refractory ASUC. Median time from admission to CsA initiation was 5 days (IQR 4–6 d) and median initial dose was 8 mg/kg/d (IQR 7–8 mg/kg/d). At admission, the median CRP was 26 (IQR 14–95) and Truelove and Witt’s severity criteria met in 21/37 (57%). 70% of patients (26/37) avoided colectomy during the index admission. No parameters were demonstrated to predict need for acute colectomy. Median follow-up after hospital discharge was 3 years (IQR 2-5years). For those who avoided acute colectomy, median duration of therapy was 4 months (IQR 2.5-5months) with bridging to azathioprine (24/26, 92%), vedolizumab (1/26, 4%), or 5-ASA (1/26, 4%). Estimated colectomy-free survival in responders were 84%, 84% and 78% at 12, 24, and 60 months. No parameters were shown to predict colectomy-free survival. Comparable colectomy-free outcomes were obtained for contemporaneous IFX-treated ASUC patients in our hospital. 9 of 26 patients remained biologic-naïve and colectomy-free after a median of 3 years. Estimated colectomy and biologic-free survival were 51%, 47% and 18% at 12, 24, and 60 months. 15 patients experienced adverse events, which were all mild and self-limiting. There were 3 infective complications. No patients required drug cessation and no serious adverse events associated with parenteral CsA occurred. Conclusion In this cohort, oral CsA was a safe, well tolerated and effective rescue therapy for steroid-refractory ASUC. A proportion of patients remain biologic and colectomy-free for up to 5 years. Given the feasibility to bridge to effective maintenance therapies, including newer biologics, oral CsA should be considered as a rescue therapy in ASUC and avoids many of the side effects associated with intravenous CsA.

Hypoalbuminemia and Bandemia Predict Failure of Infliximab Rescue Therapy in Acute Severe Ulcerative Colitis.

Infliximab rescue therapy is effective in patients with corticosteroid refractory acute severe ulcerative colitis, but predictors of response remain poorly understood. We aimed to identify predictors of colectomy in this high-risk patient population. Patients hospitalized with acute severe ulcerative colitis who received infliximab after failing intravenous corticosteroid therapy between July 2012 and June 2017 were retrospectively identified. Stepwise regression with backward elimination was used to identify predictors of colectomy at 90days and 1year. Ninety-day and 1-year colectomy rates were compared between the patients who received 5mg/kg and 10mg/kg IFX rescue dose. Sixty-three patients met the eligibility criteria. Twenty-nine patients received 5mg/kg, and 34 received 10mg/kg infliximab dose. Serum albumin on admission (OR 0.10; p = 0.04) and band neutrophil percentage at the time of infliximab administration (OR 1.21; p = 0.02) were independent predictors of 90-day colectomy. A combination of serum albumin ≤ 2.5g/dl and band neutrophil count ≥ 13% had a 100% positive predictive value for 90-day colectomy. Unadjusted 90-day and 1-year colectomy rates were similar in the 5mg/kg and 10mg/kg infliximab groups. After adjusting for confounding factors, 10mg/kg infliximab dose was potentially protective for 90-day (OR 0.07; p = 0.06) but not for 1-year colectomy (OR 0.19; p = 0.16). Bandemia and low serum albumin are independent predictors of failure of infliximab rescue therapy in acute severe ulcerative colitis. Serum albumin ≤ 2.5g/dl and band neutrophil count ≥ 13% had a 100% positive predictive value for 90-day colectomy.

P095 Association between tissue oncostatin M expression and infliximab response in corticosteroid refractory acute severe ulcerative colitis

P095 Association between tissue oncostatin M expression and infliximab response in corticosteroid refractory acute severe ulcerative colitis

High-Dose Infliximab Rescue Therapy for Hospitalized Acute Severe Ulcerative Colitis Does Not Improve Colectomy-Free Survival

Optimization strategies with infliximab (IFX) are increasingly used as rescue therapy for steroid refractory acute severe ulcerative colitis (ASUC). We aim to determine if intensified IFX induction improves colectomy rate and identifies outcome predictors. Hospitalized adult patients who received IFX for ASUC between 2010 and 2016 were identified. We compared standard inductions (5mg/kg) vs high-dose induction (10mg/kg) with 3-month colectomy rate as primary outcome. Seventy-two patients (62.5% male, median age 38.5) were identified. Thirty-seven patients (51.3%) received 5mg/kg IFX and 35 received 10mg/kg. Baseline clinical, biochemical and endoscopic parameters were well matched between these two groups. 10mg/kg was more likely to be used by clinicians from 2014 onwards (p < 0.001). Three-month colectomy rate was 9.7%; which was not significantly different between the standard (5.4%) and high-dose (14.3%) IFX induction (p = 0.205). CRP ≥ 60 (OR 10.9 [95% CI 1.23-96.50], p = 0.032), hemoglobin ≤ 90g/L (OR 15.6 [95% CI 2.61-92.66], p = 0.036) and albumin < 30g/L (OR 9.4 [95% CI 1.06-83.13], p = 0.044) were associated with increased risk of colectomy at 3months in univariate regression analysis. Use of high-dose infliximab rescue therapy did not improve 3-month colectomy-free survival in this cohort. Tailored use in high-risk patients may be beneficial although further validation is required.

Post-Operative Morbidity and Mortality of a Cohort of Steroid Refractory Acute Severe Ulcerative Colitis: Nationwide Multicenter Study of the GETECCU ENEIDA Registry

Despite the increased use of rescue medical therapies for steroid refractory acute severe ulcerative colitis, mortality related to this entity still remains high. We aimed to assess the mortality and morbidity related to colectomy and their predictive factors in steroid refractory acute severe ulcerative colitis, and to evaluate the changes in mortality rates, complications, indications of colectomy, and the use of rescue therapy over time. We performed a multicenter observational study of patients with steroid refractory acute severe ulcerative colitis requiring colectomy, admitted to 23 Spanish hospitals included in the ENEIDA registry (GETECCU) from 1989 to 2014. Independent predictive factors of mortality were assessed by binary logistic regression analysis. Mortality along the study was calculated using the age-standardized rate. During the study period, 429 patients underwent colectomy, presenting an overall mortality rate of 6.3% (range, 0-30%). The main causes of death were infections and post-operative complications. Independent predictive factors of mortality were: age ≥50 years (OR 23.34; 95% CI: 6.46-84.311; p < 0.0001), undergoing surgery in a secondary care hospital (OR 3.07; 95% CI: 1.01-9.35; p = 0.047), and in an emergency setting (OR 10.47; 95% CI: 1.26-86.55; p = 0.029). Neither the use of rescue medical treatment nor the type of surgical technique used (laparoscopy vs. open laparotomy) influenced mortality. The proportion of patients undergoing surgery in an emergency setting decreased over time (p < 0.0001), whereas the use of rescue medical therapy prior to colectomy progressively increased (p > 0.001). The mortality rate related to colectomy in steroid refractory acute severe ulcerative colitis varies greatly among hospitals, reinforcing the need for a continuous audit to achieve quality standards. The increasing use of rescue therapy is not associated with a worse outcome and may contribute to reducing emergency surgical interventions and improve outcomes.

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.

PTH-096 Oral Ciclopsorin in Steroid Refractory, Acute, Severe Ulcerative Colitis

IntroductionCiclosporin (CsA) has been shown to be effective in treatment of steroid refractory severe ulcerative colitis and reducing the need for colectomy1. Most published evidence concerns intravenous infusions; however oral...