Infliximab Rescue Research Articles

Infliximab rescue therapy in acute severe ulcerative colitis: more does not equal better

Infliximab rescue therapy in acute severe ulcerative colitis: more does not equal better

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

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

P962 Clinical and endoscopic remission at 3 months after Acute Severe Ulcerative Colitis is predictive of maintenance therapy outcomes at 12 months - Results from PREDICT UC

Abstract Background The optimal maintenance regimen after rescue therapy for Acute Severe Ulcerative Colitis (ASUC) is unknown. We aimed to evaluate prospectively the impact of different maintenance regimens after successful infliximab (IFX) rescue, along with factors associated with Month 12 remission. Methods Clinical responders at 3 months from PREDICT UC, a randomised trial (NCT02770040) comparing standard and intensified IFX rescue strategies, were evaluated in this prospective cohort study up to Month 12. Maintenance therapies were as follows: (1) Thiopurine monotherapy (azathioprine or mercaptopurine) for thiopurine naïve patients or prior suboptimal thiopurine therapy (TP); (2) Combination thiopurine and IFX therapy 5mg/kg 8-weekly for thiopurine-experienced patients (IFX+TP combo); (3) IFX monotherapy 5mg/kg 8-weekly for thiopurine-intolerant patients (IFX mono). All patients received oral 5-aminosalicylates. Clinical and endoscopic assessments were performed at baseline (Month 3) and Month 12. Clinical remission was defined as a partial Mayo score of 0-1 and endoscopic remission as Mayo Endoscopic Score (MES) of 0-1. Results Of 138 patients randomised, 79 entered the maintenance phase. Of these, 56 (71%) received TP, 16 (20%) received IFX+TP combo and 7 (9%) received IFX mono. Baseline characteristics were similar across the 3 maintenance groups. At 12 months, 42 patients (53%) were in clinical remission, 44 patients (56%) were in endoscopic remission, and one patient underwent colectomy. The 3 maintenance groups had similar rates of clinical remission (TP 55%, IFX+TP combo 56%, IFX mono 29%; P=0.39) and endoscopic remission (TP 55%, IFX+TP combo 56%, IFX mono 57%; P=0.99) at 12 months. Clinical Remission On univariable and multivariable analysis, no factors were associated with clinical remission at 12 months, including baseline CRP, albumin, partial Mayo score, MES, UCEIS or maintenance strategy. Endoscopic Remission Factors associated with endoscopic remission at 12 months included baseline partial Mayo score of 0 (OR 3.36, 95% CI 1.24-9.10, P=0.017), MES of 0-1 (OR 3.48, 95% CI 1.08-11.27, P=0.037) and UCEIS of 0-1 (OR 3.30, 95% CI 1.24-8.76, P=0.016). However, a partial Mayo score cut-off of 0-1 did not reach significance (OR 3.46, P=0.09). No factors associated with endoscopic remission were identified on multivariable analysis. Conclusion In steroid-refractory ASUC patients who received IFX rescue, clinical and endoscopic remission at Month 3 were associated with endoscopic remission at Month 12, particularly among patients with greater depth of remission. Month 3 assessment helps identify patients at higher risk of disease progression for whom more intensive treatment may be required.

P972 Short and long-term outcomes after acute severe ulcerative colitis in children: A Canadian single centre experience

Abstract Background The short and long-term course of ulcerative colitis (UC) following an episode of acute severe UC (ASUC) in children is insufficiently characterized. We aimed to assess contemporary outcomes in children hospitalized with ASUC. Methods This was a retrospective cohort study of children aged 2-17 years hospitalized with ASUC between 2010 and 2022 at a tertiary center in London, Ontario, Canada. All data were recorded using standardised Case Report Forms, de-identified, and entered into a central database registry using Research Electronic Data Capture (REDCap) Steroid non-response was defined as requirement of medical rescue therapy or colectomy. Results A total of 58 children hospitalized with ASUC were included (male: 55.2% [n =32], mean age at admission: 12.2 ± 3.5 years). The majority had extensive colitis (82.4% [n = 42]) at the time of diagnosis. 74% (n = 43) presented within one year of symptom onset and 31% (n = 18) had ASUC as their index presentation with UC. 15.5% (n = 9) of patients had prior purine analogues and 20.7% (n = 12) had received biologics prior to ASUC presentation. Median Pediatric Ulcerative Colitis Activity Index (PUCAI) score on admission was 65.0 (IQR: 60.0 – 75.0). After intravenous corticosteroid therapy 68.9% (n = 40) responded to steroids. Of the patients with steroid non-response (31% [n = 18]), 3.4% (2/58) underwent colectomy and 27.6% (16/58) patients received infliximab rescue therapy. Median PUCAI score was significantly lower on day 3 between steroid responders and steroid non-responders (37.5 vs 60, p <0.01). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 7.4% (4/54) and 8% (4/50) respectively. Short term and long-term hospitalization rates for UC exacerbation following discharge was 25.9% (14/54) and 16% (8/50) respectively. Similar rates of long-term colectomy and hospitalizations were observed between steroid responders and non-responders. On univariate analysis, no statistically significant factors associated with steroid non-response were identified. Conclusion 17% of patients hospitalized for ASUC required colectomy within 12 months of presentation. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates are still high. Future research should focus on earlier identification and treatment of children at high risk of exacerbation to prevent complications.

P550 Short and long-term outcomes after acute severe ulcerative colitis in adults: A 12 year Canadian experience in the post biologic era

Abstract Background Patients with acute severe ulcerative colitis (ASUC) are at increased risk of colectomy following an episode of acute severe exacerbation. Medical rescue therapy in steroid non-responders has reduced the need for emergency colectomy. However, impact of biologics on longer-term colectomy risk is unclear. Methods A retrospective cohort study of adult patients aged ≥18 years hospitalized with acute exacerbation of UC requiring hospitalization and managed with intravenous corticosteroids between 2010 and 2022 at two regional hospitals in London, Ontario, Canada. Steroid non-response was defined as requirement of medical rescue therapy or colectomy. Results A total of 264 adults hospitalized with ASUC were included in the analysis (male: 51.1% [n=136], mean age at admission: 40.8±17.8 years). The majority had extensive colitis (71.3% [n=169]) at the time of diagnosis. 46.3% (n=118/255) presented within one year of disease onset and 23% (n=61) had ASUC as their first presentation with UC. 25.7% (n=66/257) of patients had prior purine analogues and 23.3% (60/257) had previous biologics prior to ASUC presentation. After admission, 55.7% (n=147) responded to intravenous corticosteroids. Of the steroid non-responders, 37.5% (n=99) patients were managed with infliximab rescue therapy and only one patient received tofacitinib rescue therapy. Median CRP, stool frequency and Lindgren index score were statistically significant between steroid responders and non-responders (Table 1). A higher proportion of steroid non-responders had prior exposure to biologics or tofacitinib compared to steroid responders (31.9% vs 16.3%, p<0.01). On multivariate analysis for various factors predicting steroid non-response, assessment by Oxford criteria on day 3 was the only factor that was statistically significant (odds ratio 4.70 (95% CI 1.06-20.8), p = 0.04). Oxford criteria on day 3 had a sensitivity, specificity of 58.6% and70.8%, respectively for predicting steroid non-response. 8% (n=21) required colectomy during index admission. An additional 13% (n = 32) underwent colectomy within 12 months of discharge, for which there was no difference between steroid responders and non-responders (12.2% vs 14.7%). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 8% (20/245) and 5.4% (12/223) respectively. Hospitalization with UC exacerbation rate following discharge was 17% (38/223). Conclusion 8% of patients admitted for ASUC require colectomy during the same admission and additional 13% required colectomy within 12 months of discharge. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates remain high.

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.

453 The Optimal Timing of Colectomy for Acute Severe Ulcerative Colitis

Abstract Aim Acute severe ulcerative colitis (ASUC) is a medical emergency which, if left untreated, can be fatal. Some cases require colectomy. The timing of this operation is important to reduce post-operative morbidity. The primary study aim is to assess whether the timing of this operation impacts upon post-operative outcome. The secondary aim of this study is to determine whether pre-operative blood albumin level may be able to predict post-operative complication rates. Method All patients who underwent colectomy and ileostomy formation for ASUC at Bristol Royal Infirmary between 2010-2020 were identified. Patient demographic information, duration of pre-operative hospital stays, blood results and post-operative complications up until the most recent follow up were recorded. Patients undergoing elective colectomy for ulcerative colitis were analysed separately. Results Twenty-one ASUC admissions were identified who were all treated with intravenous steroids for a median of 9 (range 1-18) days before colectomy. 16 patients (76%) received either ciclosporin or infliximab rescue therapies. Median admission CRP was 41 (range 4-231). Median admission blood albumin was 29 (range 16-38). <30-day and >30-day post-operative complication rates were 52% (11/21) and 25% (5/20) respectively. Conclusions Previous literature shows significant association between the length of pre-operative medical therapy and post-operative complications. Surgeons can learn from them, so far, negative findings of our study. A surgeon’s own clinical judgement is the most important factor in the decision of when to take an ASUC patient to theatre. Biomarkers can aid a decision but cannot be used as a solitary justifier for the timing of colectomy.

ThTP7.9 The Optimal Timing of Colectomy for Acute Severe Ulcerative Colitis

Abstract Aims Acute severe ulcerative colitis (ASUC) is a medical emergency which, if left untreated, can be fatal. Some cases require colectomy. The timing of this operation is important to reduce post-operative morbidity. The primary study aim is to assess whether the timing of this operation impacts upon post-operative outcome. The secondary aim of this study is to determine whether pre-operative blood albumin level may be able to predict post-operative complication rates. Methods All patients who underwent colectomy and ileostomy formation for ASUC at Bristol Royal Infirmary between 2010-2020 were identified. Patient demographic information, duration of pre-operative hospital stays, blood results and post-operative complications up until the most recent follow up were recorded. Patients undergoing elective colectomy for ulcerative colitis were analysed separately. Results Twenty-one ASUC admissions were identified who were all treated with intravenous steroids for a median of 9 (range 1-18) days before colectomy. 16 patients (76%) received either ciclosporin or infliximab rescue therapies. Median admission CRP was 41 (range 4-231). Median admission blood albumin was 29 (range 16-38). <30-day and >30-day post-operative complication rates were 52% (11/21) and 25% (5/20) respectively. Conclusions Previous literature shows significant association between the length of pre-operative medical therapy and post-operative complications. Surgeons can learn from the, so far, negative findings of our study. A surgeon’s own clinical judgement is the most important factor in the decision of when to take an ASUC patient to theatre. Biomarkers can aid a decision, but cannot be used as a solitary justifier for the timing of colectomy.

Early Flexible Sigmoidoscopy Improves Clinical Outcomes in Acute Severe Ulcerative Colitis.

Guidelines recommend performing a flexible sigmoidoscopy in patients hospitalized with acute severe ulcerative colitis (ASUC). However, it is unclear if time to sigmoidoscopy affects relevant clinical outcomes. We aimed to assess the impact of early sigmoidoscopy on clinical outcomes using a well-characterized cohort of patients with ASUC. This is a single-center, retrospective study of all patients hospitalized with ASUC from January 1, 2012 to November 1, 2021. Early sigmoidoscopy was defined as occurring within 72 hours of admission while delayed sigmoidoscopy was defined as occurring >72 hours after admission. Primary outcomes were cumulative days of intravenous (IV) corticosteroid (CS) use, length of hospital stay, and colectomy rates. Secondary outcomes were time to infliximab (IFX) rescue and inpatient opioid medication use. A total of 112 patients hospitalized with ASUC who underwent sigmoidoscopy were included in the analysis. Eighty-seven patients (78%) had early sigmoidoscopy and 25 (22%) had delayed sigmoidoscopy. Patients in the early sigmoidoscopy group were exposed to significantly fewer days of IV CS (4.5 vs 9.2 days; P < .001), had shorter hospital stays (6.4 vs 19.3 days; P < .001), and shorter time to IFX rescue (3.5 vs 6.4 days; P = .004). Rates of colectomy in the early and delayed sigmoidoscopy groups were 17% versus 28%, respectively (P = .23). Longer time to sigmoidoscopy was associated with a 16% increased risk of colectomy (HR = 1.16, P = .002). In this well-characterized cohort, early sigmoidoscopy in ASUC was associated with favorable clinical outcomes. These findings highlight the benefits of early sigmoidoscopy in patients with ASUC. Larger prospective studies are needed to corroborate these findings.

Infliximab Rescue Therapy in Pediatric Severe Colitis

IntroductionClinical remission has been achieved with infliximab in patients with refractory ulcerative colitis (UC). However, there is conflicting data regarding its effectiveness as rescue therapy in adult acute severe colitis. Furthermore, pediatric inflammatory bowel disease (IBD) is associated with more severe disease that may be less amenable to attempted rescue. We reviewed our experience and outcomes with pediatric severe colitis after attempted inpatient rescue with infliximab. MethodsA single-institution, retrospective review was conducted of pediatric patients with UC or indeterminate colitis who received inpatient rescue infliximab therapy from 1/2000 to 1/2019. Rescue infliximab therapy was considered if a child failed non-biologic therapy or progressed to fulminant or toxic colitis. Primary outcome was failed therapy resulting in colectomy. A p-value of <0.05 determined significance. ResultsThirty patients met inclusion criteria. The median age at administration of rescue infliximab treatment was 14 years [IQR 13,17]. Rescue therapy with infliximab was successful in 33% (n = 10), while 67% (n = 20) underwent colectomy. Children on maintenance steroids were less likely to be successfully rescued with infliximab and require colectomy (p = 0.03). Children requiring colectomy had a longer hospital stay (p = 0.03), more abdominal radiographs (p = 0.01), and were on a longer duration of antibiotics (p = <0.01) compared to children who were successfully rescued with infliximab. There was no difference in baseline vital signs or laboratory abnormalities between the two groups. ConclusionIn severe acute ulcerative or indeterminate colitis cases where infliximab has not been previously used, rescue infliximab can be used to avoid colectomy but has a high failure rate. Level of EvidenceIV. Type of StudyRetrospective study.

P356 CRAB Score, An Indian Insight into in hospital and long-term Colectomy following Acute Severe Ulcerative Colitis (ASUC)

Abstract Background Oxford and Swedish index were developed to predict in hospital colectomy in ASUC and not for long-term prediction say one to two years. Oxford index, Swedish index and other predictors of Colectomy are based on western Data. In hospital colectomy rates were also rapidly decreasing during the last two decades with the advent of rescue therapy like infliximab and cyclosporine but the colectomy rate within one or two years of ASUC is not significantly reduced. Study by Alice et al had shown that with advent of infliximab and cyclosporine rescue therapy oxford index no longer predicts in-hospital colectomy rates also in addition to its shortcoming in predicting long-term colectomy rates. Our study Aims to find out the predictors of in hospital and long-term colectomy in an Indian cohort of ASUC patients. Methods Prospective observational study conducted in department of Medical Gastroenterology medical college Trivandrum over a period of 5 years (2015-2020). ASUC is defined by Truelove Witts criteria Patients with ASUC were followed up for a period of 24 months to look for progression to colectomy. Results Total 81 patients were taken up for the study (47 males and 34 females). 15 patients progress to colectomy during the follow up period of 24 months (11 patients had colectomy done during the same hospital admission and 4 patients during the follow up period of 24 months). Among the variables analysed Albumin, CRP and Hb were significant in predicting colectomy in 24 months. On regression analysis CRP and Albumin were independent predictors of 24-month colectomy and coefficient of Beta was multiplied to albumin and CRP and total score was obtained and termed it as CRAB (CRP + Albumin) score (CRAB score = CRP*0.2 – Albumin*0.26). This score was plotted to AUROC and the score has AUROC of 0.923 and at a Score of &amp;gt;0.4 has sensitivity of 82 and specificity of 92% 24-month chance for colectomy following ASUC. The score was validated in a validation cohort of 31 patients and in validation cohort also at &amp;gt;0.4 the score has sensitivity of 83 and specificity of 96% in predicting colectomy. Those without pancolitis and those with a precipitating factor for colitis exacerbation won’t progress to Colectomy. Conclusion CRAB score is a simple prognostic score that can predict 24-month colectomy in ASUC patients with high sensitivity and specificity. Those without pancolitis and those with a precipitating factor for colitis exacerbation won’t progress to Colectomy.

Dose-Intensified Infliximab Rescue Therapy on Short-term Colectomy Rates in Patients With Severe Ulcerative Colitis.

Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang City, Liaoning Province, China

S2792 A Tale of Three Stomas: A Challenging Case of Inflammatory Bowel Disease

Introduction: Inflammatory bowel disease (IBD) and diverticular disease have many overlapping sequelae. It can be difficult to distinguish between them in an acute presentation. Here, we report a challenging case of IBD that originally presented as complicated diverticular disease. We highlight the diagnostic and management considerations. Case Description/Methods: A 75-year-old female without personal or family history of IBD presented in June 2021 with abdominal pain and fever, was diagnosed with uncomplicated diverticulitis and treated with a course of antibiotics. She recovered clinically but presented in July 2021 with worsening abdominal pain and bloody diarrhea. She was found on imaging to have a colonic perforation and abscess. She was taken for a Hartmann procedure with sigmoidectomy and colostomy formation, with surgical pathology suggestive of acute diverticulitis. Abdominal pain and bloody ostomy output continued. She presented to our medical center in September 2021. Evaluation showed deep ulcerations and spontaneous friability, concerning for IBD. She was started on steroids but she proved refractory. We then offered rescue infliximab, after which she clinically improved. She was maintained on infliximab as an outpatient. Before repeat endoscopic evaluation, she presented again to the hospital with abdominal pain and was found to have another colonic perforation. She underwent a completion subtotal colectomy, extensive lysis of adhesions and received an end ileostomy. Pathology showed severely active chronic pancolitis with ulceration. She currently is in clinical remission, not currently on any IBD therapy. Discussion: The diagnosis for this patient has proved difficult, given her initial acute presentation. Complicated diverticulitis has overlapping features with IBD, and is more prevalent than IBD. It is less prevalent in the IBD population, with one study showing prevalence in ulcerative colitis (UC) of 10.8% compared to 27.8% in healthy controls. Endoscopic evaluation was important in understanding the presence of IBD, though it has been challenging to define a distinct entity of UC versus Crohn’s disease given her history of abscess and colonic perforation. The rate of intra-abdominal abscess in UC is low but has been described. In one single center analysis, the rate of intra-abdominal abscess in UC vs Crohn’s disease with 0.8% vs 2.4%, respectively. After surgical recovery, we plan for small bowel evaluation to further delineate the extent of inflammation.Figure 1.: Image from colonoscopy from 9/21/21 showing erythema, ulceration, friability.

Dose-Intensified Infliximab Rescue Therapy for Severe Ulcerative Colitis Does Not Reduce Short-term Colectomy Rates or Increase Postoperative Complications.

Dose-intensified rescue therapy with infliximab for hospitalized patients with ulcerative colitis has become increasingly popular in recent years. However, there is ongoing debate about both the efficacy of these regimens to reduce the rate of colectomy and the associated risks of increased infliximab exposure. The purpose of this study was to compare the colectomy and postoperative complication rates in hospitalized patients with severe ulcerative colitis receiving standard infliximab induction therapy (3 doses of 5 mg/kg at weeks 0, 2, and 6) and dose-intensified regimens including a higher weight-based dosing or more rapid interval. This was a retrospective cohort study. This study was conducted at an academic tertiary care hospital. A total of 145 adult patients received inpatient rescue infliximab therapy for the treatment of ulcerative colitis between 2008 and 2020. The primary outcome was colectomy rate within 3 months of rescue therapy. Secondary outcomes include mid-term colectomy rates, as well as perioperative complications in patients receiving colectomy within 3 months of rescue infliximab initiation. The proportion of dose-intensified regimens increased over time. Unadjusted 3-month colectomy rates were 14% in patients who received standard rescue infliximab dosing, 16% in patients given a single dose-escalated dose, and 24% in patients given multiple inpatient dose-escalated doses. These rates were not statistically significantly different. Of the patients requiring colectomy within 3 months of infliximab rescue, those who received multiple inpatient doses of dose-escalated therapy had a higher percentage of colectomy during the initial hospitalization but a lower rate of perioperative complications. This study was limited by the use of retrospective data and the limited power to account for the heterogeneity of disease. No significant difference was found in colectomy rates between patients receiving standard or dose-intensified regimens. However, dose-intensified regimens, including multiple inpatient doses given to patients with more severe disease, were not associated with a greater risk of perioperative complications. See Video Abstract at http://links.lww.com/DCR/B864 . ANTECEDENTES:La terapia de rescate de dosis intensificada con infliximab para pacientes hospitalizados con colitis ulcerosa se ha vuelto cada vez más popular en los últimos años. Sin embargo, existe un debate en curso sobre la eficacia de estos regímenes para reducir la tasa de colectomía y los riesgos asociados a una mayor exposición al infliximab.OBJETIVO:El propósito de este estudio fue comparar las tasas de colectomía y complicaciones posoperatorias en pacientes hospitalizados con colitis ulcerosa grave que recibieron terapia estándar de inducción de infliximab (3 dosis de 5 mg/kg en las semanas 0, 2, 6) y regímenes de dosis intensificada que incluyen una dosificación más alta basada en el peso o intervalo más rápido.DISEÑO:Fue un estudio de cohorte retrospectivo.ENTORNO CLÍNICO:Este estudio se realizó en un hospital académico de tercer nivel.PACIENTES:Un total de 145 pacientes adultos que recibieron terapia de rescate con infliximab para el tratamiento de la colitis ulcerosa entre 2008 y 2020.PRINCIPALES MEDIDAS DE VALORACIÓN:El resultado principal fue la tasa de colectomía dentro de los 3 meses posteriores a la terapia de rescate. Los resultados secundarios incluyen tasas de colectomía a mediano plazo, así como las complicaciones perioperatorias en pacientes que reciben colectomía dentro de los 3 meses posteriores al inicio de infliximab de rescate.RESULTADOS:La proporción de regímenes de dosis intensificada aumentó con el tiempo. Las tasas de colectomía de 3 meses no ajustadas fueron del 14% en los pacientes que recibieron dosis estándar de infliximab de rescate, del 16% en los pacientes que recibieron una dosis única escalonada y del 24% en los pacientes que recibieron múltiples dosis hospitalarias escalonadas. Estas tasas no fueron estadísticamente significativas. De los pacientes que requirieron colectomía dentro de los 3 meses posteriores al rescate de infliximab, aquellos que recibieron terapia de múltiples dosis hospitalarias escalonadas tuvieron un mayor porcentaje de colectomía durante la hospitalización inicial pero una menor tasa de complicaciones perioperatorias.LIMITACIONES:Datos retrospectivos y poder limitado para explicar la heterogeneidad de la enfermedad.CONCLUSIONES:No se encontraron diferencias significativas en las tasas de colectomía entre los pacientes que recibieron regímenes estándar o de dosis intensificada. Sin embargo, los regímenes de dosis intensificadas, incluidas múltiples dosis hospitalarias administradas a pacientes con enfermedad más grave, no se asociaron con un mayor riesgo de complicaciones perioperatorias. Consulte Video Resumen en http://links.lww.com/DCR/B864 . (Traducción-Dr. Ingrid Melo ).

Increased Hospitalization for IBD Patients Seen in the ER During the COVID-19 Pandemic.

BackgroundDuring the COVID-19 pandemic, the focus of many health care systems shifted in order to prioritize and allocate resources toward treating those affected by COVID-19. What this has meant for other patient populations remains unclear. We aimed to determine if there have been changes to acute care access for patients with inflammatory bowel disease (IBD) during the COVID-19 pandemic.MethodsA retrospective cohort study was performed in IBD patients seen during (March 1, 2020 to August 31, 2020) and before (March 1, 2019 to August 31, 2019) the COVID-19 pandemic. IBD-related emergency room (ER) access, hospitalization, inpatient care and follow-up and post-discharge ER access were assessed.ResultsA total of 1229 participants were included. A higher proportion of patients accessed ER during the pandemic (44.6% versus 37.2%, P = 0.0097). A higher proportion of hospitalizations resulted from IBD-related ER visits during the pandemic period (41.6% versus 32.4%, OR = 1.48, 95% CI = 1.14 to 1.94, P = 0.0047), though length of stay was shorter (7.13 ± 8.95 days versus 10.11 ± 17.19 days, P = 0.015) and use of rescue infliximab was less. No change was seen in inpatient surgical intervention. Despite similar proportions of follow-up appointments post-hospital discharge (pre-pandemic, 77.9% versus pandemic, 78.3%), more ER visits occurred in the first 30 days following hospitalization for patients in the pandemic cohort (24.4% versus 11.1%, P = 0.0015).ConclusionThese data highlight the need for ER services and hospitalization amongst IBD patients during the COVID-19 pandemic. This suggests that a return to pre-pandemic IBD care infrastructure is needed to mitigate the need for acute care access.

P304 Intensified versus conventional infliximab induction in acute severe steroid-refractory Ulcerative Colitis

Abstract Background Infliximab is effective as salvage therapy in severe steroid-refractory Ulcerate Colitis. However, up to one third of patients do not respond to this treatment and require surgery. There is still insufficient evidence regarding the benefits of intensified infliximab induction regimens in this setting. Methods Retrospective study including, 51 patients meeting the Truelove and Witts criteria for severe acute Ulcerative Colitis with refractoriness to intravenous steroids requiring infliximab rescue therapy. We compared patients under conventional infliximab induction therapy (n=29) with patients performing an intensified infliximab induction regimen (n=22), defined as a higher dose/shorter interval of treatment during induction. Results There was no difference in respect to median age [IQR] (32.0 [27.0–43.0] vs, 42.0 [29.0–58.0], p=0.116), and male gender (69.0 % vs, 63.6%, p=, 0.458) between patients with conventional or intensified infliximab. Compared to patients with conventional induction, patients under optimized infliximab presented reduced admission to intermediary/intensive care unit (4.5% vs, 31.0%, p=, 0.019), and surgery (13.6% vs, 41.4%, p=, 0.031). There were no differences in deaths (3.4% vs, 9.1%, p=0.396), readmission rates (17.2% vs, 28.6%, p=, 0.270), and median duration [IQR] of hospitalization (19.0 [10.5–31.0] vs, 12.0 [8.0–15.5], p=0.094) between patients with conventional or intensified regimens. In a multivariate analysis, the use of an intensified infliximab induction regimen was associated with a lower risk of surgery (OR, 0.224, 95%CI [0.054–0.929], p=, 0.039). Conclusion In this small cohort, there was some suggestions that intensified infliximab induction may improve treatment outcomes in acute severe steroid refractory Ulcerative Colitis.

P520 Very early intestinal ultrasound predicts intravenous corticosteroid failure in hospitalized severe ulcerative colitis patients

Abstract Background Intestinal ultrasound (IUS) is an objective marker for inflammation in ulcerative colitis (UC). Few studies have examined if repeated IUS can predict treatment outcomes in UC. Our aim was to determine if IUS changes after 48±24h of intravenous corticosteroids can predict treatment outcomes in hospitalized patients with severe UC. Methods We performed a blinded observational multicenter study at three university hospitals in Denmark. Bowel wall thickness (BWT), colour doppler signals (CDS), inflammatory mesenteric fat (I-fat), haustration, and bowel wall stratification (BWS) were assessed before treatment initiation and after 48±24h. Treatment response was assessed with a partial Mayo score (pMayo) at day 6±1, defined as a ≥30% and ≥3 point reduction with either a rectal bleeding subscore of 0 or 1 OR a decrease in rectal subscore ≥1 point. If infliximab was administered earlier (≥3 days), pMayo was evaluated at administration. The treating physician was blinded to the IUS findings, and the IUS examiner was blinded to all non-IUS disease parameters. Results Fifty-six patients were recruited between February 2019 and March 2021 (Table 1). Thirty-seven (66%) responded to intravenous corticosteroid therapy within seven days of treatment, while 19 (34%) did not. There was no difference in baseline BWT between groups. However, at follow-up, significant differences between responders and non-responders were identified in both absolute BWT (median 3.1mm vs 4.9mm), absolute reduction ΔBWT (median -1.9mm vs -0.2mm), and percentage reduction (median -35.9% vs -4.1%) all p&amp;lt;0.005, (Figure 1). Receiver operating characteristic curve analysis for BWT at 48±24h to predict non-response showed an area under the curve of 0.85. BWT ≥4mm had a sensitivity of 84.2 (95% CI 60.4–96.6), specificity of 75.7 (95% CI 58.8–88.2), a negative predictive value of 90.3 (95% CI 74.2–98.0), and a positive predictive value of 64 (95% CI 42.5–82.0) for determining non-response. The absence of I-fat, and the presence of BWS and haustration all had significant odds ratio (OR) for detecting response at follow-up. However, BWT was the only significant parameter in the multivariable analysis and, thereby, the most important parameter for response assessment (BWT &amp;gt;20% reduction adjusted OR 10.8 (95% CI 2.5 - 56.6) and BWT ≤4mm adjusted OR 8.8 (95% CI 1.9 - 51.3), both p&amp;lt;0.01). Conclusion Changes in IUS BWT after 48±24h following intravenous corticosteroid treatment in hospitalized severe ulcerative colitis patients, identify responders with high accuracy. IUS might be utilized as an early corticosteroid non-response marker to guide accelerated rescue infliximab regimes.

Infliximab rescue therapy in a patient with acute severe ulcerative colitis and coronavirus disease 2019 followed by Escherichia coli 0157:H7 infection: a case report

The management of patients with acute severe ulcerative colitis and SARS-CoV-2 presents a clinical challenge. We report on the first case of a patient with acute severe ulcerative colitis and mild coronavirus disease 2019 (COVID-19) who received rescue infliximab therapy, followed by a relapse caused by enterohemorrhagic Escherichia coli 0157:H7. The treatment challenges we faced were biologic therapy administration during active COVID-19, about which little was known at the time, and how to treat EHEC due to the risk of hemolytic uremic syndrome. Acute severe ulcerative colitis was treated with rescue infliximab therapy, and enteric infection with an antibiotic, both with satisfactory clinical response. The decision to induce biologic therapy for inflammatory bowel disease relapse in SARS-CoV-2-positive patients should be made on a case-to-case basis and should be driven by the dominant disease. Our patient tested positive for SARS-CoV-2, but actually had mild disease. At the same time, she had acute severe ulcerative colitis, so we started anti-tumor necrosis factor therapy despite serological tests and the recommendation to delay biological therapy administration for two-weeks. Second, due to severity of the first flare, COVID-19, and the patient's general condition, we opted for an antibiotic treatment of Escherichia coli 0157:H7 while monitoring the parameters of potential hemolytic uremic syndrome development.

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.