Antibiotic-dependent Pouchitis Research Articles

P366 Risk factors and outcomes of chronic antibiotic-refractory pouchitis in Korean ulcerative colitis patients: a single center retrospective study

Abstract Background Chronic inflammation of the pouch after total proctocolectomy with ileal pouch-anal anastomosis (IPAA) remains a morbid complication in ulcerative colitis (UC). The goal of this study was to investigate risk factors and clinical outcomes of chronic antibiotic-refractory pouchitis (CARP) in Korean patients with UC. Methods This was a single center retrospective study on patients with UC who underwent total proctocolectomy with IPAA at Asan Medical Center in Korea between January 1987 and December 2022. CARP was defined as failure to respond to a 4-week course of a single antibiotic, needing more than 4 weeks of therapy with 5-aminosalicylates, steroids, immunomodulators or biologics/small molecules, while chronic antibiotic-dependent pouchitis (CADP) was defined as more than 3 episodes of pouchitis per year or persistent symptoms requiring long-term antibiotics to maintain disease remission. Primary outcomes were endoscopic remission defined as complete mucosal healing of chronic pouchitis and pouch failure defined as the requirement of diverting loop ileostomy or pouch excision. Univariable and multivariable logistic regression analysis were used to identify risk factors of CARP. Results A total of 251 patients were included and 232 were analyzed (Male, 57.3%; Current smoker, 13.4%; Median age at surgery, 44 years; Disease duration at surgery, 4 years; Previous exposure to biologics/small molecules, 23.7%; Extra-intestinal manifestations, 8.2%; Preoperative cytomegalovirus infection, 19.4%). The most common cause of surgery was steroid refractoriness (50.9%), followed by dysplasia/colorectal cancer (26.7%). The median time from surgery to chronic pouchitis was 48 months (interquartile range 23.5–100.0). Among 74 patients (31.9%) with chronic pouchitis, 31 patients (13.4%) were CARP and 43 patients (18.5%) were CADP. The most frequent endoscopic phenotype according to Chicago classification was focal inflammation of the pouch in all groups (chronic pouchitis, 47.3%; CARP, 35.5%; CADP, 55.8%). Patients with CARP were less likely to have concomitant probiotics compared with CADP (29.0% vs 72.1%; p<0.01). Endoscopic remission rate in chronic pouchitis, CARP, and CADP were 14.9% (11/74), 9.7% (3/31), and 18.6% (8/43), respectively (Table 1). Pouch failure rate in chronic pouchitis, CARP, and CADP were 13.5% (10/74), 16.1% (5/31), and 11.6% (5/43), respectively (Table 1). In a multivariable analysis, current smoking status was positively associated with CARP development (OR: 3.56; 95% confidence interval 1.33–9.52; p=0.01). Conclusion Current smoker with UC who underwent IPAA had a higher risk of CARP. Concomitant use of probiotics was less likely to be associated with developing CARP.

Extraintestinal Manifestations and Family History of Inflammatory Bowel Disease Increase the Risk of Pouchitis in a State-Level Epidemiology Study.

Our understanding of the epidemiology of inflammatory conditions of the pouch and effectiveness of treatment is largely based on selected populations. We created a state-level registry to evaluate the incidence of pouchitis and the effectiveness of treatments used in an initial episode of pouchitis. In a state-level retrospective cohort of all patients undergoing proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis between January 1, 2018, and December 31, 2020, we evaluated the incidence of pouchitis and compared the proportion of patients developing recurrent pouchitis and chronic antibiotic-dependent pouchitis according to initial antibiotic therapy. A total of 177 patients underwent surgery with 49 (28%) developing pouchitis within the 12 months after the final stage of IPAA. Patients with extraintestinal manifestations of inflammatory bowel disease (IBD) were significantly more likely to develop pouchitis within the first 12 months after IPAA (adjusted odds ratio 2.45, 95% confidence interval 1.03-5.81) after adjusting for family history of IBD (adjusted odds ratio 3.50, 95% 1.50-8.18). When comparing the proportion of patients who developed recurrent pouchitis or chronic antibiotic-dependent pouchitis with those who experienced an isolated episode of pouchitis, there were no significant differences among the initial antibiotic regimens used. In a state-level examination of outcomes after IPAA for ulcerative colitis, patients with extraintestinal manifestations of IBD were more likely to develop pouchitis; however, the initial antibiotic regimen chosen did not seem to affect long-term outcomes.

Dietary Patterns Are Not Associated With Disease Activity Among Patients With Inflammatory Conditions of the Pouch in a Prospective Cohort.

Evidence-based recommendations regarding the influence of diet on inflammatory conditions of the pouch after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) are limited. We analyzed dietary patterns at enrollment in a prospective registry of patients with 1 of 4 inflammatory conditions of the pouch (acute pouchitis, chronic antibiotic-dependent pouchitis, chronic antibiotic refractory pouchitis, and Crohn's disease of the pouch). We analyzed dietary intake by disease activity at enrollment and then compared dietary patterns among patients who remained in remission throughout the 12-month follow-up to those patients who experienced a disease relapse. We also compared dietary patterns among patients with inflammatory conditions of the pouch to the United States Department of Agriculture (USDA) recommended daily goals. Among 308 patients, there were no differences in dietary patterns among patients with 1 of the 4 disease states at enrollment. Additionally, among the 102 patients in remission at baseline, there were no significant differences noted among patients who went on to experience a disease flare in the 12 months after enrollment compared to those patients who remained in remission. However, patients with inflammatory conditions of the pouch demonstrated decreased intake of several food groups and macronutrients including dairy, fruits, vegetables, whole grains, and fiber when compared to USDA recommendations. In a prospective cohort, we demonstrated no impact of dietary patterns on disease activity. The relative deficiencies in several food groups and macronutrients among patients after IPAA indicate the potential role of targeted nutritional counseling in this population.

Very Early Pouchitis Is Associated with an Increased Likelihood of Chronic Inflammatory Conditions of the Pouch.

Chronic inflammatory conditions of the pouch are common after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). We aimed to investigate the relationship between acute pouchitis within 180days of the final stage of IPAA surgery (very early pouchitis) and the future development of chronic antibiotic dependent pouchitis (CADP) and Crohn's-like disease of the pouch (CLDP). We performed a retrospective cohort study, evaluating patients who underwent proctocolectomy with IPAA between January 1, 2004 and December 31, 2016. Multivariable logistic regression was used to evaluate the relationship between very early pouchitis and the development of CADP and CLDP. Among 626 patients undergoing IPAA for UC, 137 (22%) developed very early pouchitis, 75 (12%) developed CADP, and 59 (9%) developed CLDP in a median follow-up of 5.18years (interquartile range 0.94-10.8years). Very early pouchitis was associated with a significant increase in the odds of developing CADP (adjusted odds ratio [aOR3.65, 95% CI 2.19-6.10) as was primary sclerosing cholangitis (aOR 3.97, 95% CI 1.44-11.0). Very early pouchitis was associated with increased odds for developing CLDP (aOR 2.77, 95% CI 1.54-4.98) along with a family history of inflammatory bowel disease (aOR 2.10, 95% CI 1.11-3.96). In this cohort, very early pouchitis was associated with an increased risk of developing CADP and CLDP. These findings highlight very early pouchitis as a unique risk factor for chronic inflammatory conditions of the pouch and the need for future studies evaluating potential strategies for secondary prophylaxis strategies in this population.

DOP70 Crohn’s Disease Like Inflammation of The Pouch is a Distinct Type of Pouchitis

Abstract Background Pouchitis occurs in up to 80% of patients with ulcerative colitis (UC) after total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA). The pathogenesis of pouchitis is unclear, but is thought to involve a complex interaction between the microbiome and mucosal immune system. To examine the underlying pathophysiological mechanisms of pouchitis, the present study aims to simultaneously define immuno-histological and microbial parameters associated with different pouch phenotypes. Methods Endoscopic biopsies from the pre-pouch ileum (PI) and the pouch body (PB) were obtained from 51 subjects age>18 who underwent TPC with IPAA, n=48 for UC and n=3 for familial adenomatous polyposis (FAP). Mucosal mononuclear cells (MMC) were isolated from the intra-epithelial compartment (IEC) and lamina propria (LP) and examined for lymphoid, myeloid and innate immune subsets by multiparameter flow-cytometry (FC). Histological sections were examined by two pathologists, blinded to clinical identifiers and scored for inflammatory parameters that included neutrophilic activity, lymphoplasmacytic infiltration, eosinophilia, villous atrophy and submucosal fibrosis. Metagenomic sequencing of stool was performed and analyzed for microbial beta and alpha diversity. Results IPAA subjects were classified into the following phenotypes: normal pouch (NP) n=15 (29.4%), acute pouchitis (AP) n=9 (17.6%), chronic antibiotic dependent pouchitis (CADP) n=9 (17.6%), Crohn’s disease like pouch inflammation (CDLPI) n=15 (29.4%), and FAP NP n=3 (5.9%). Among subjects with NP, the PB had a higher frequency of naïve-CD4+ and CD8+ T cells, central memory- CD4+ T cells, and naïve B cells and a lower frequency of homeostatic IELs relative to the PI (Fig. 1A). Immune remodeling of the PB was further confirmed on histology that demonstrated increased lymphoid aggregates and decreased IELs. Subjects with CDLPI had significantly higher levels of inflammation, chronicity, and lymphoid aggregates but decreased IELs in the PI than NP or AP patients (Fig. 1B and 1C). In contrast to immune parameters, the composition of the microbiota in non-inflamed UC pouches was more similar to inflamed UC pouches than to FAP pouches. Alpha diversity and genus relative abundance differences between UC and FAP pouch stool samples were not statistically significant (Fig. 1D). Conclusion CDLPI represents a distinct entity of pouchitis that is associated with heightened levels of chronic inflammation relative to AP despite similarities in microbiota.

S763 Twenty Percent of Patients With Inflammatory Conditions of the Pouch Demonstrate a More Refractory Disease State Within Twelve Months of Enrollment in a Multicenter Prospective Registry

Introduction: Up to 80% of patients will develop pouchitis after proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, and approximately 10% will develop Crohn’s disease (CD) of the pouch. We designed a geographically diverse, eight-center, prospective registry to study the disease course among patients with one of four inflammatory conditions of the pouch. The aim of this study was to evaluate patterns of changes in diagnosis during the first 12 months after enrollment. Methods: We enrolled patients with a confirmed diagnosis of acute pouchitis, chronic antibiotic dependent pouchitis (CADP), chronic antibiotic refractory pouchitis (CARP), or CD of the pouch. Diagnoses were based on standardized criteria and we obtained detailed clinical and demographic data at the time of enrollment. Patients completed follow-up assessments at 3, 6, and 12 months after enrollment, with treating physicians confirming their respective diagnoses at each time point. Associations between clinical and demographic data at baseline and a switch in diagnosis to a more refractory disease state were analyzed using chi-square testing. Results: We enrolled 318 patients (10% acute pouchitis, 27% CADP, 12% CARP, and 51% CD of the pouch). During the first 12 months after enrollment, 31 of the 157 patients (20%) without CD of the pouch at enrollment switched diagnosis to a more refractory disease state, with 20 of 31 (65%) patients ultimately being diagnosed with CD of the pouch. Among 7 patients with acute pouchitis who switched diagnoses, 5 were diagnosed with CADP, 1 with CARP, and 1 with CD of the pouch. Among 19 patients with CADP who switched diagnoses, 4 were diagnosed with CARP and 15 were diagnosed with CD of the pouch. Four patients with CARP had a change in diagnosis to CD of the pouch during the study period. Patients who experienced a change in diagnosis were significantly more likely to be current smokers when compared to patients with no change in diagnosis during the study period (23% vs. 5%, p=0.001, Table). Conclusion: In a prospective registry of 318 patients from eight centers in the United States, 20% of patients without CD of the pouch at enrollment experienced a change in diagnosis to a more refractory inflammatory condition of the pouch during the first 12 months after enrollment. Patients who were current smokers were more likely to change diagnoses, and may represent a high risk group for earlier intervention and targeted smoking cessation efforts after IPAA. Table 1. - Comparison of Baseline Demographics and Clinical Characteristics of Patients with an Inflammatory Condition of the Pouch and a Change in Diagnosis to those with No Change in Diagnosis Change in Diagnosis within 12 Months of Enrollment n=31 No Change in Diagnosis within 12 Months of Enrollment n=287 p-value Median IQR Median IQR Current Age 50 44-59 52 38-62 0.873 n % n % Female Sex 12 39 129 45 0.636 Race >0.999 White 29 94 263 92 Black 1 3 16 6 Other 1 3 8 3 Hispanic ethnicity 3 10 7 2 0.063 BMI 0.271 Normal 17 55 114 40 Overweight 7 23 99 34 Obese 7 23 71 25 Disease extent prior to surgery 0.447 Proctitis 2 6 19 7 Left-sided colitis 5 16 22 8 Extensive colitis 19 31 151 61 Unknown 4 13 52 18 Indication for surgery >0.999 Medically-refractory colitis 29 94 256 89 Dysplasia/colorectal cancer 1 3 13 5 Medically refractory + dysplasia/colorectal cancer 0 0 8 3 Other 1 3 9 3 Number of stages in surgery 0.590 1 2 6 35 12 2 10 32 114 40 Modified 2 3 10 19 7 3 15 48 103 36 IPAA surgery performed at current medical center 20 65 181 63 >0.999 Primary Sclerosing Cholangitis 2 6 23 8 >0.999 Clostridiodes difficile infection prior to IPAA 4 13 42 15 >0.999 Smoker at the time of colectomy 2 6 15 5 0.678 Current smoker 7 23 13 5 0.001 NSAIDs in the prior two weeks 12 39 104 36 0.846

S752 Early Pouchitis Is Associated With an Increased Likelihood of Chronic Antibiotic Dependent Pouchits and Crohn’s-Like Disease of the Pouch

Introduction: Approximately 80% of patients will develop pouchitis at some point after an IPAA for ulcerative colitis (UC), with 17% of patients developing chronic antibiotic dependent pouchitis (CADP) and and 10% developing Crohn’s-like disease of the pouch. Few reliable risk factors for these chronic inflammatory conditions of the pouch have been identified. We aimed to investigate the relationship between early pouchitis, defined as acute pouchitis within the first 180 days of the final stage of IPAA surgery, and the future development of CADP and Crohn’s-like disease of the pouch. Methods: We performed a retrospective cohort study, evaluating patients who underwent proctocolectomy with IPAA at our center between January 1, 2004 and December 31, 2016. Multivariable logistic regression was used to evaluate the relationship between early pouchitis and the development of CADP and Crohn’s-like disease of the pouch, adjusting for other relevant clinical and demographic factors. Results: Among 626 patients undergoing IPAA for UC, 137 (22%) developed early pouchitis, 75 (12%) developed CADP, and 59 (9%) developed Crohn’s-like disease of the pouch. Patients developing early pouchitis were significantly more likely to be of Hispanic ethnicity compared to patients who did not develop early pouchitis (5.6% vs. 1.4%, p=0.006, Table). Early pouchitis was associated with a significant increase in the odds of developing CADP (adjusted odds ratio [aOR] 3.65, 95% CI 2.19-6.10). A preoperative diagnosis of PSC was also associated with an increase in the odds of developing CADP (aOR 3.97, 95% CI 1.44-11.0). Early pouchitis was also associated with an increased likelihood of developing Crohn’s-like disease of the pouch (aOR 2.68, 95% CI 1.50-4.80) as was a family history of inflammatory bowel disease (aOR 2.10, 95% CI 1.11-3.96). The median duration of follow up for all patients in the study was 5.18 years (interquartile range 0.94 – 10.8 years). Conclusion: In a cohort of patients with UC who underwent IPAA, the development of pouchitis within the first 180 days of surgery was associated with an increased risk of developing CADP and Crohn’s-like disease of the pouch. These findings highlight early pouchitis as a unique risk factor for chronic pouch-related disorders and the need for future studies evaluating potential interventions including secondary prophylaxis strategies in this population. Table 1. - Univariate comparison of demographic and clinical characteristics of patients with and without pouchitis in the two years following an ileal pouch-anal anastomosis Patients without early pouchitis (n=489) Patients with early pouchitis (n=137) p-value Median IQR Median IQR Age at surgery, in years 40.3 28.8-52.4 43.1 33.7-54.5 0.094 Disease duration prior to surgery 5.9 2.2-14.2 6.3 2.0-13.6 0.854 n % n % Race 0.923 White 424 89.3 121 89.0 Non-White 51 10.7 15 11.0 Hispanic 6 1.4 7 5.6 0.006 Family history of Crohn's disease or ulcerative colitis 83 16.2 14 20.0 0.421 Indication for surgery 0.059 Medically-refractory colitis 376 76.9 118 86.1 Dysplasia or cancer 72 14.7 11 8.0 Other indications/multiple indications 41 8.4 8 5.8 Disease extent prior to surgery 0.405 Proctitis 23 5.0 3 2.3 Left-sided colitis 133 29.1 40 30.8 Extensive colitis 301 65.9 87 66.9 Stages involved in IPAA surgery 0.977 1 92 18.9 24 17.5 2 173 35.5 51 37.2 Modified 2 183 37.5 11 37.2 3 40 8.2 51 8.0 Abscess or pelvic sepsis after IPAA surgery 94 19.2 23 16.8 0.518 Evidence of an IPAA leak immediately after IPAA surgery 38 7.8 8 5.8 0.444 Primary Sclerosing Cholangitis 13 2.7 6 4.4 0.299 Medications used prior to colectomy Systemic aminosalicylate 380 77.7 115 83.9 0.113 Topical aminosalicylate 230 47.0 72 52.6 0.253 Thiopurine 299 61.2 91 66.4 0.256 Methotrexate 58 11.9 9 6.6 0.077 Anti-TNF 252 51.5 69 50.4 0.809 Vedolizumab 11 2.3 6 4.4 0.175 Cyclosporine 13 2.7 13 9.5 < 0.001 Prednisone use at the time of last stage of surgery 192 39.3 58 42.7 0.487

Prevalence of Clostridioides difficile Infection After Ileal Pouch-anal Anastomosis in Patients With Chronic Antibiotic-dependent Pouchitis and Crohn's-like Disease of the Pouch.

Recurrent or chronic antibiotic therapy is a therapeutic hallmark of chronic antibiotic-dependent pouchitis (CADP) or Crohn's-like disease of the pouch. Antibiotics alter the gut microbiome, which may increase the risk of Clostridioides difficile infection (CDI). The aim of this study was to determine the prevalence of CDI in patients with CADP and Crohn's-like disease of the pouch. We conducted a retrospective cohort study of patients with CADP or Crohn's-like disease of the pouch at a tertiary academic medical center. The primary outcome was prevalence of CDI. Secondary outcomes included antibiotic therapy at the time of CDI diagnosis, treatment regimens for CDI, and subsequent outcomes. Overall, 18 of 198 (9.1%) included patients developed CDI. Treatment with antibiotics at the time of CDI diagnosis occurred in 7 of 18 (39%) patients. Preoperative history of CDI was significantly associated with increased risk of developing CDI following ileal pouch anal anastomosis (IPAA) compared with those with no prior history of CDI (12 of 18 [67%] vs 11 of 180 [6%]; P < .001). In 16 of 18 (89%) patients, CDI treatment was initiated with predominantly oral vancomycin (72%) or metronidazole (17%). Although chronic inflammatory conditions of the pouch arise postoperatively, the prevalence of CDI in this population appears to be similar compared with the general population of patients with inflammatory bowel disease prior to and post IPAA. Preoperative CDI appears to be the greatest risk for postoperative CDI and may require extra vigilance in the assessment of CDI after IPAA.

Treatment Patterns and Standardized Outcome Assessments Among Patients With Inflammatory Conditions of the Pouch in a Prospective Multicenter Registry.

BackgroundMuch of our understanding about the natural history of pouch-related disorders has been generated from selected populations. We designed a geographically diverse, prospective registry to study the disease course among patients with 1 of 4 inflammatory conditions of the pouch. The primary objectives in this study were to demonstrate the feasibility of a prospective pouch registry and to evaluate the predominant treatment patterns for pouch-related disorders.MethodsWe used standardized diagnostic criteria to prospectively enroll patients with acute pouchitis, chronic antibiotic-dependent pouchitis (CADP), chronic antibiotic refractory pouchitis (CARP), or Crohn’s disease (CD) of the pouch. We obtained detailed clinical and demographic data at the time of enrollment, along with patient-reported outcome (PRO) measures.ResultsWe enrolled 318 patients (10% acute pouchitis, 27% CADP, 12% CARP, and 51% CD of the pouch). Among all patients, 55% were on a biologic or small molecule therapy. Patients with CD of the pouch were more likely to use several classes of therapy (P < .001). Among patients with active disease at the time of enrollment, 23% with CARP and 40% with CD of the pouch were in clinical remission at 6 months after enrollment.ConclusionsIn a population where most patients had refractory inflammatory conditions of the pouch, we established a framework to evaluate PROs and clinical effectiveness. This infrastructure will be valuable for long-term studies of real-world effectiveness for pouch-related disorders.

Impact of fecal microbiota transplantation on chronic recurrent pouchitis in ulcerative colitis with ileo-anal anastomosis: study protocol for a prospective, multicenter, double-blind, randomized, controlled trial

BackgroundAlmost 15% of patients with ulcerative colitis (UC) will require a proctocolectomy with ileal pouch–anal anastomosis (IPAA) as a result of fulminant colitis, dysplasia, cancer, or medical refractory diseases. Around 50% will experience pouchitis, an idiopathic inflammatory condition involving the ileal reservoir, responsible for digestive symptoms, deterioration in quality of life, and disability. Though the majority of initial cases of pouchitis are easily managed with a short course of antibiotics, in about 10% of cases, inflammation of the pouch becomes chronic with very few treatments available.Previous studies have suggested that manipulating the composition of intestinal flora through antibiotics, probiotics, and prebiotics achieved significant results for treating acute episodes of UC-associated pouchitis. However, there is currently no established effective treatment for chronic antibiotic-dependent pouchitis. Fecal microbiota transplantation (FMT) is a novel therapy involving the transfer of normal intestinal flora from a healthy donor to a patient with a medical condition potentially caused by the disrupted homeostasis of intestinal microbiota or dysbiosis.MethodsOur project aims to compare the delay of relapse of chronic recurrent pouchitis after FMT versus sham transplantation. Forty-two patients with active recurrent pouchitis after having undergone an IPAA for UC will be enrolled at 12 French centers. The patients who respond to antibiotherapy will be randomized at a ratio of 1:1 to receive either FMT or sham transplantation.DiscussionOn April 30, 2014, the World Health Organization published an alarming report on antibiotic resistance. Finding an alternative medical treatment to antibiotics in order to prevent relapses of pouchitis is therefore becoming increasingly important given the risk posed by multiresistant bacteria. Moreover, if the results of this study are conclusive, FMT, which is less expensive than biologics, could become a routine treatment in the future.Trial registrationClinicalTrials.gov, NCT03524352. Registered on 14 May 2018.

A Personalized Approach to Managing Patients With an Ileal Pouch-Anal Anastomosis.

Quality of life after ileal pouch-anal anastomosis (IPAA) surgery is generally good. However, patients can be troubled by pouch-related symptoms and pouch disorders that can be inflammatory, mechanical/surgical, and functional. Management of patients with IPAA begins with measures to maintain a healthy pouch such as optimizing pouch function, providing tailored advice on a healthy diet and lifestyle, screening for and addressing metabolic complications of IPAA, pouch surveillance, and risk stratification for risk of pouchitis and pouch failure. Pouchitis is the most common inflammatory disorder. Primary pouchitis is a spectrum currently classified into three progressive phases—an antibiotic-responsive, an antibiotic-dependent, and an antibiotic-refractory phase. It is predominately microbially mediated in acute antibiotic-responsive pouchitis and predominately immune mediated in chronic antibiotic-refractory pouchitis (CARP). Secondary prophylaxis is recommended for recurrent antibiotic-responsive and for antibiotic-dependent pouchitis. Secondary causes of antibiotic-refractory pouchitis should be ruled out before a diagnosis of CARP is made. CARP is best classified as primary sclerosing cholangitis associated, immunoglobulin G4-associated, and autoimmune. Primary sclerosing cholangitis-associated CARP can be treated with budesonide or oral vancomycin. Early recognition of immunoglobulin G4-associated pouchitis minimizes ineffective antibiotic use. Autoimmune CARP can be managed in a manner similar to UC. The current place of immunosuppressives in the treatment algorithm depends on availability and early access to biological agents. Vedolizumab and ustekinumab are the preferred first- and second-line biologics for autoimmune CARP owing to their efficacy, better side effect profile, and low immunogenicity and need for concomitant immunomodulatory therapy. Antitumor necrosis factor should be reserved for autoimmune CARP failing the above and for CD of the pouch. There are no guidelines for the surveillance of pouches for dysplasia. Incidence varies based on a patient's risk. Since incidence is low, a risk-stratified approach is recommended.

Pouchitis: diagnosis and management.

Pouchitis is the most common complication in patients who undergo ileal pouch-anal anastomosis (IPAA), occurring more frequently in patients with ulcerative colitis. Pouchitis - the inflammation of the pouch - can be due to idiopathic or secondary causes. Chronic antibiotic-dependent pouchitis (CADP) and chronic antibiotic-resistant pouchitis (CARP) are the most difficult forms of chronic idiopathic pouchitis to treat. Crohn's disease of the pouch may develop de novo in ulcerative colitis patients following colectomy with IPAA. It carries a high risk for pouch failure, and its diagnosis and management are challenging. The purpose of this review is to illustrate the present trends in the diagnosis and treatment of idiopathic pouchitis and Crohn's disease of the pouch. The use of the newer biologic agents, vedolizumab and ustekinumab, has shown promising results in patients with CADP, CARP, and Crohn's disease of the pouch. Fecal microbiota transplantation has also been reported to have encouraging preliminary results in small studies and case series for the treatment of chronic pouchitis. Promising new treatments are emerging for difficult-to-treat forms of pouchitis. Larger prospective and head-to-head comparative studies among the various treatments are needed to evaluate the efficacy and safety of these agents across the pouchitis subgroups, and to identify predictors of response.

2111 Antibiotic Dependent Pouchitis Successfully Managed With Vedolizumab in a Patient With a Prior History of Renal Malignancy

INTRODUCTION: Pouchitis is a known complication of ileal pouch-anal anastomosis (IPAA). The mechanism is unknown but is felt to be due to altered bacterial flora and then a dysregulated immune response in the pouch. Although one of the mainstays of treatment is antibiotics, long-term use for patients with chronic pouchitis (CP) may not be addressing the underlying mechanism while also subjecting the patient to the risk of prolonged antibiotics. New limited data supports the use of biologics in the management of CP. We report a case of a man with a history of chronic antibiotic dependent pouchitis (CADP) and prior malignancy who was successfully managed with vedolizumab. CASE DESCRIPTION/METHODS: 44 year-old male with past medical history of ulcerative colitis status-post IPAA, renal oncytoma status-post resection (2017), non-insulin dependent diabetes, and fatty liver disease presented with persistently increased bowel movements. He endorsed weeks of twenty bowel movements per day to the point that he was awoken from sleep. He presented to urgent care where he was started on ciprofloxacin and metronidazole yet he continued to be symptomatic. He then presented to gastroenterology clinic and was started on xifaxin. He subsequently underwent a pouchoscopy showing CP (confirmed by biopsy). After some discussion, the plan was to initiate a biologic as he was refractory to antibiotics. However he was concerned about starting systemic immunosuppression given his prior malignancy. As he was post resection with reported cure and no plan to undergo further treatment, he was started on vedolizumab. On vedolizumab he endorsed resolution of symptoms with a dramatic improvement in quality of life. DISCUSSION: The challenge in management of CP arises when there is dependence on antibiotics and continued symptoms. Recent studies support the use of biologics (i.e. vedolizumab). These papers document resolution of symptoms and endoscopic improvement of disease. However there has yet to be robust data evaluating the efficacy or safety of biologics for this indication in those with prior malignancy. In this case there was initial hesitation but given the remote nature and clinical stability of the malignancy as well as gut-specificity of vedolizumab the decision was made to pursue therapy. This case highlights the successful use of vedolizumab for the treatment of CADP. The use of biologics in CP needs to further be studied, especially in a cost-benefit analysis looking further into outcomes related to long-term antibiotic use.

Chronic Antibiotic Dependent Pouchitis Is Associated With Older Age at the Time of Ileal Pouch Anal Anastomosis (J-pouch) Surgery.

BackgroundRisk factors for the development of chronic antibiotic dependent pouchitis (CADP) are not well understood.MethodsUsing multivariable logistic regression, we compared clinical factors between 194 patients with acute antibiotic responsive pouchitis or CADP.ResultsIndividuals with CADP were significantly older (40.9 vs 30.8 years, P < 0.001) and demonstrated a longer disease duration before IPAA (10.3 vs 7.0 years, P = 0.004). Age ≥55 years at the time of IPAA was significantly associated with CADP (adjusted odds ratio = 4.35, 95% confidence interval = 1.01–18.7).ConclusionsAlthough older age should not represent a barrier to IPAA, further studies evaluating etiologies of this association are warranted.

P048 Type and durability of antibiotic therapy among patients with chronic antibiotic dependent pouchitis

BACKGROUND: The management of chronic antibiotic dependent pouchitis (CADP) is associated with significant morbidity and burden to patients with an ileal pouch-anal anastomosis (IPAA). When individuals fail to respond to standard antibiotic therapy for pouchitis, little guidance is available in choosing subsequent antibiotic regimens. We performed a retrospective study to evaluate specific antimicrobials as well as duration of therapy among patients treated for CADP in our multidisciplinary IBD center. METHODS: We identified patients with CADP between January 1, 2009 and December 1, 2016. Patients diagnosed with Crohn’s disease of the pouch and acute antibiotic responsive pouchitis were excluded. For each individual with CADP, we analyzed the type and duration of up to 4 antibiotic regimens. Standard descriptive statistics are presented, including medians and interquartile ranges (IQR) for duration assessments and Wilcoxon-rank sum testing for comparisons of duration of antibiotic therapy. RESULTS: A total of 288 patients were evaluated for pouch related disorders during the study period. From the initial population, 90 (31%) were excluded due to a diagnosis of Crohn's disease of the pouch and 75 (26%) were excluded due to a diagnosis of acute antibiotic responsive pouchitis. In total, there were 123 patients (53% male, mean age at time of IPAA 40.9 years) who were diagnosed with CADP. Most patients underwent a 2-stage IPAA and had pancolitis prior to colectomy. In the majority of patients (93/123; 75%), the first antibiotic regimen consisted of a fluoroquinolone alone (43%) or a fluoroquinolone in combination with either metronidazole (30%) or another antibiotic (2%). Metronidazole was used in 15%, and other antibiotics in 10% of the patients. Of the 123 patients, 93%, 76%, and 59% needed a second, third, or fourth antibiotic regimen, respectively. The use of fluoroquinolones alone or in combination decreased to 54%, 48%, and 40% of patients for the second, third, and fourth regimen. In particular, amoxicillin/clavulanate, sulfamethoxazole/trimethoprim, rifaximin and doxycycline were increasingly used in the third and fourth antibiotic approach (31% and 42%, respectively). The duration of the different antibiotic regimens varied, but fluoroquinolones alone were given for a significantly longer duration during the first 4 consecutive regimens compared to other antibiotics indicating a better persistence of therapy (regimen 1 median fluoroquinolone duration 32 weeks vs others 7.5 weeks (IQR 4–36), P &lt; 0.001; regimen 2 median 20 weeks vs 8 weeks (IQR 4–28), P = 0.038; regimen 3 median 21 weeks vs 8 weeks (IQR 4–36), P = 0.005; regimen 4 median 20 weeks vs 10 weeks (IQR 4–20), P = 0.011). CONCLUSION(S): In a retrospective cohort of patients with CADP, we found that standard therapy with a fluoroquinolone alone or in combination was most common as the initial treatment for CADP. Although fluoroquinolones in particular demonstrated significant longevity, over time the proportion of the population treated with alternative antibiotic regimens such as amoxicillin/clavulanate, sulfamethoxazole/trimethoprim, doxycycline, and rifaximin increased presumably due to loss of response to standard therapy. Further studies are needed to individualize the therapeutic approach and determine the optimal antibiotic regimen with greatest durability and long-term response for this challenging patient population.

P591 Low donor microbial engraftment after combined endoscopic and oral faecal microbiota transplant (FMT) in patients with antibiotic dependent pouchitis

P591 Low donor microbial engraftment after combined endoscopic and oral faecal microbiota transplant (FMT) in patients with antibiotic dependent pouchitis

Combined Endoscopic and Oral Fecal Microbiota Transplantation in Patients with Antibiotic-Dependent Pouchitis: Low Clinical Efficacy due to Low Donor Microbial Engraftment

Background and Objective: A significant number of pouch patients develop antibiotic-dependent pouchitis (ADP). Microbial dysbiosis is thought to be a major driver of clinical symptoms in ADP. The objective of this proof of concept study was to evaluate safety, efficacy, and donor microbial engraftment of an intensified fecal microbiota transplant (FMT) consisting of a single endoscopic FMT followed by daily oral FMT for 2 weeks in patients with ADP. Methods: We performed a prospective placebo-controlled double-blind FMT trial in patents with established ADP and planned to enroll 20 patients in this proof of concept study. In case of non-response, patients were offered an optional open label active FMT treatment. The endpoints were safety, clinical remission without need for antibiotics during 16 weeks of follow-up, quantitative changes of fecal calprotectin (FCP), and engraftment of donor FMT as determined by metagenomic sequencing of the V4 region of the 16S rRNA gene. Results: Due to a lower than expected clinical remission rate and low FMT engraftment, enrollment in the study was stopped prematurely after 6 patients were included. All 6 patients enrolled in the placebo-controlled portion failed to respond and needed antibiotic rescue therapy shortly after FMT. FCP increased in the majority of patients in the setting of relapse after FMT. In the active open label FMT extension study 1 out of 5 patients achieved antibiotic-free clinical remission. FMT engraftment after active FMT was observed only in this single patient, whereas engraftment of donor FMT occurred in none of the other patients receiving active FMT, paralleling the lack of clinical response. Conclusions: Low donor FMT engraftment resulted in low clinical efficacy of FMT in patients with ADP. Before embarking on larger clinical trials with FMT in patients with ADP or other forms of pouchitis, it is mandatory to explore approaches for superior FMT engraftment.

Vedolizumab for treatment of chronic refractory pouchitis: a systematic review with pool analysis.

about 1%-2% of patients with chronic refractory pouchitis, in the context of ulcerative colitis, end up with a permanent ileostomy. The aim of this systematic review was to collect all published studies involving patients treated with vedolizumab for chronic refractory or antibiotic-dependent pouchitis and then pool the data regarding the effectiveness of this therapeutic strategy. a MEDLINE and Web of Science search of all studies published in English until March 17, 2019 was conducted using the terms "vedolizumab and pouchitis". seven studies with a total of 44 patients with chronic pouchitis were included. Twenty-three out of 44 patients (52.3%) had undergone previous treatment with anti-tumor necrosis factor (TNF) drugs. At week 12, 33 out of 44 patients (75%) reported clinical improvement. Endoscopic improvement, evaluated within 6 months of the start of vedolizumab therapy, was obtained in 28 out of the 38 patients in whom such data were available (73.7%). this first systematic review published in the literature on this issue suggests that vedolizumab has significant efficacy in chronic refractory or antibiotic-dependent pouchitis, also in patients who failed to respond to other treatments including those with anti-TNF agents.

Su1883 - Older age at the Time of Ileal Pouch-Anal Anastomosis Surgery is Associated with Chronic Antibiotic Dependent Pouchitis in a Multidisciplinary Inflammatory Bowel Disease Center

Su1883 - Older age at the Time of Ileal Pouch-Anal Anastomosis Surgery is Associated with Chronic Antibiotic Dependent Pouchitis in a Multidisciplinary Inflammatory Bowel Disease Center

Long-term follow-up of the use of maintenance antibiotic therapy for chronic antibiotic-dependent pouchitis

ObjectiveRestorative proctolectomy is considered the procedure of choice in patients with ulcerative colitis who have failed medical therapy. Chronic pouchitis occurs in 10%–15% of patients, which often require long-term antibiotics...