AGA Clinical Practice Guideline on the Management of Pouchitis and Inflammatory Pouch Disorders.

BACKGROUND & AIMS: Pouchitis is the most common complication after restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. This American Gastroenterological Association (AGA) guideline is intended to support practitioners in the management of pouchitis and inflammatory pouch disorders. METHODS: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, conduct an evidence synthesis, and develop recommendations for the prevention and treatment of pouchitis, Crohn's-like disease of the pouch, and cuffitis. RESULTS: The AGA guideline panel made 9 conditional recommendations. In patients with ulcerative colitis who have undergone ileal pouch-anal anastomosis and experience intermittent symptoms of pouchitis, the AGA suggests using antibiotics for the treatment of pouchitis. In patients who experience recurrent episodes of pouchitis that respond to antibiotics, the AGA suggests using probiotics for the prevention of recurrent pouchitis. In patients who experience recurrent pouchitis that responds to antibiotics but relapses shortly after stopping antibiotics (also known as "chronic antibiotic-dependent pouchitis"), the AGA suggests using chronic antibiotic therapy to prevent recurrent pouchitis; however, in patients who are intolerant to antibiotics or who are concerned about the risks of long-term antibiotic therapy, the AGA suggests using advanced immunosuppressive therapies (eg, biologics and/or oral small molecule drugs) approved for treatment of inflammatory bowel disease. In patients who experience recurrent pouchitis with inadequate response to antibiotics (also known as "chronic antibiotic-refractory pouchitis"), the AGA suggests using advanced immunosuppressive therapies; corticosteroids can also be considered in these patients. In patients who develop symptoms due to Crohn's-like disease of the pouch, the AGA suggests using corticosteroids and advanced immunosuppressive therapies. In patients who experience symptoms due to cuffitis, the AGA suggests using therapies that have been approved for the treatment of ulcerative colitis, starting with topical mesalamine or topical corticosteroids. The panel also proposed key implementation considerations for optimal management of pouchitis and Crohn's-like disease of the pouch and identified several knowledge gaps and areas for future research. CONCLUSIONS: This guideline provides a comprehensive, patient-centered approach to the management of patients with pouchitis and other inflammatory conditions of the pouch.

Antibiotic Use in the 12 Months Prior to Ileal Pouch-Anal Anastomosis Increases the Risk for Pouchitis.

BACKGROUND & AIMS: Pouchitis is the most common complication after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC); however, clinical and environmental risk factors for pouchitis remain poorly understood. We explored the relationship between specific clinical factors and the incidence of pouchitis. METHODS: We established a population-based cohort of all adult persons in Denmark undergoing proctocolectomy with IPAA for UC from 1996-2020. We used Cox proportional hazard modeling to assess the impact of antibiotic, nonsteroidal anti-inflammatory drug (NSAID) exposure, and appendectomy on diagnosis of acute pouchitis in the first 2 years after IPAA surgery. RESULTS: Among 1616 eligible patients, 46% developed pouchitis in the first 2 years after IPAA. Antibiotic exposure in the 12 months before IPAA was associated with an increased risk of pouchitis (adjusted hazard ratio [aHR], 1.41; 95% confidence interval [CI], 1.22-1.64) after adjusting for anti-tumor necrosis factor alpha use and sex. Compared with persons without any antibiotic prescriptions in the 12 months before IPAA, the risk of pouchitis was increased in those with 1 or 2 courses of antibiotics in that period (aHR, 1.30; 95% CI, 1.11-1.52) and 3 or more courses (aHR, 1.77; 95% CI, 1.41-2.21). NSAID exposure in the 12 months before IPAA and appendectomy were not associated with risk of acute pouchitis (P = .201 and P = .865, respectively). CONCLUSIONS: In this population-based cohort study, we demonstrated that antibiotic exposure in the 12 months before IPAA is associated with an increased risk of acute pouchitis. Future prospective studies may isolate specific microbial changes in at-risk patients to drive earlier interventions.

Real-World Surgical and Endoscopic Recurrence Based on Risk Profiles and Prophylaxis Utilization in Postoperative Crohn's Disease.

BACKGROUND & AIMS: Preoperative risk stratification may help guide prophylactic biologic utilization for the prevention of postoperative Crohn's disease (CD) recurrence; however, there are limited data exploring and validating proposed clinical risk factors. We aimed to explore the preoperative clinical risk profiles, quantify individual risk factors, and assess the impact of biologic prophylaxis on postoperative recurrence risk in a real-world cohort. METHODS: In this multicenter retrospective analysis, patients with CD who underwent ileocolonic resection (ICR) from 2009 to 2020 were identified. High-risk (active smoking, ≥2 prior surgeries, penetrating disease, and/or perianal disease) and low-risk (nonsmokers and age >50 y) features were used to stratify patients. We assessed the risk of endoscopic (Rutgeert score, ≥i2b) and surgical recurrence by risk strata and biologic prophylaxis (≤90 days postoperatively) with logistic and time-to-event analyses. RESULTS: A total of 1404 adult CD patients who underwent ICR were included. Of the high-risk factors, 2 or more ICRs (odds ratio [OR], 1.71; 95% CI, 1.13-2.57), active smoking (OR, 1.73; 95% CI, 1.17-2.53), penetrating disease (OR, 1.41; 95% CI, 1.02-1.94), and history of perianal disease alone (OR, 1.99; 95% CI, 1.42-2.79) were associated with surgical but not endoscopic recurrence. Surgical recurrence was lower in high-risk patients receiving prophylaxis vs not (10.2% vs 16.7%; P = .02), and endoscopic recurrence was lower in those receiving prophylaxis irrespective of risk strata (high-risk, 28.1% vs 37.4%; P = .03; and low-risk, 21.1% vs 38.3%; P = .002). CONCLUSIONS: Clinical risk factors accurately illustrate patients at risk for surgical recurrence, but have limited utility in predicting endoscopic recurrence. Biologic prophylaxis may be of benefit irrespective of risk stratification and future studies should assess this.

One-Year Comparative Effectiveness of Upadacitinib vs Tofacitinib for Ulcerative Colitis: A Multicenter Cohort Study.

INTRODUCTION: The comparative effectiveness of upadacitinib and tofacitinib for ulcerative colitis (UC) is poorly understood. METHODS: In this retrospective cohort study, we compared steroid-free clinical remission (SFCR) and endoscopic response/remission at 52 weeks among adults initiating upadacitinib or tofacitinib for UC. RESULTS: A total of 155 patients initiated upadacitinib (n = 81; 30% prior tofacitinib exposure) or tofacitinib (n = 74; 0% prior upadacitinib exposure). After inverse probability of treatment-weighted logistic regression, upadacitinib was associated with significantly higher odds of SFCR (odds ratio 3.01, 95% confidence interval 1.39-6.55) vs tofacitinib. There were no differences for endoscopic response/remission. DISCUSSION: Upadacitinib was more effective at achieving SFCR in UC at 52 weeks vs tofacitinib.

The Natural History After Ileal Pouch-Anal Anastomosis for Ulcerative Colitis: A Population-Based Cohort Study From the United States.

INTRODUCTION: There are limited data regarding the natural history after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). The principal objectives of this study were to identify 4 key outcomes in the natural history after IPAA within 1, 3, 5, and 10 years: the incidence of pouchitis, Crohn's-like disease of the pouch, use of advanced therapies after IPAA, and pouch failure requiring excision in a network of electronic health records. METHODS: We performed a retrospective cohort study in TriNetX, a research network of electronic health records. In addition to evaluating incidence rates, we also sought to identify factors associated with pouchitis and advanced therapy use within 5 years of IPAA after 1:1 propensity score matching, expressed as adjusted hazard ratios (aHRs). RESULTS: Among 1,331 patients who underwent colectomy with IPAA for UC, the incidence of pouchitis increased from 58% in the first year after IPAA to 72% at 10 years after IPAA. After propensity score matching, nicotine dependence (aHR 1.61, 95% confidence interval [CI] 1.19-2.18), antitumor necrosis factor therapy (aHR 1.33, 95% CI 1.13-1.56), and vedolizumab prior to colectomy (aHR 1.44, 95% CI 1.06-1.96) were associated with an increased risk of pouchitis in the first 5 years after IPAA. The incidence of Crohn's-like disease of the pouch increased to 10.3% within 10 years of IPAA while pouch failure increased to 4.1%. The incidence of advanced therapy use peaked at 14.4% at 10 years after IPAA. DISCUSSION: The incidence of inflammatory conditions of the pouch remains high in the current era, with 14% of patients requiring advanced therapies after IPAA.

Efficacy and Safety of Liraglutide in Patients With an Ileal Pouch-Anal Anastomosis and Chronic High Bowel Frequency: A Placebo-Controlled, Crossover, Proof-of-Concept Study.

INTRODUCTION: After colectomy with ileoanal pouch anastomosis (IPAA), many patients develop high bowel frequency (BF) refractory to antimotility agents, despite normal IPAA morphology. Low circulating levels of glucagon-like protein-1 (GLP-1), a modulator of gastroduodenal motility, have been reported after colectomy. METHODS: Double-blind crossover study of 8 IPAA patients with refractory high BF treated with daily administration of the GLP-1 receptor agonist liraglutide or placebo. RESULTS: Liraglutide, but not placebo, reduced daily BF by more than 35% ( P < 0.03). DISCUSSION: Larger randomized controlled studies are warranted to delineate the treatment potential of GLP-1 receptor agonists in IPAA patients suffering from noninflammatory high BF.

Patients With Inflammatory Bowel Disease Are at Increased Risk of Hospitalization Due to Respiratory Syncytial Virus.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at increased risk of developing respiratory infections. Respiratory syncytial virus (RSV) is a common respiratory virus with adverse outcomes in older adults. This study aimed to determine whether patients with IBD are at increased risk of a serious infection due to RSV. METHODS: We conducted a retrospective study using the multi-institutional research network TriNetX to assess the risk of hospitalization in a cohort of patients with IBD compared with that in a non-IBD control cohort with RSV infection from January 1, 2007, to February 27, 2023. One-to-one (1:1) propensity score matching was performed for demographic variables and RSV risk factors between the 2 cohorts. Risk was expressed as adjusted odds ratio (aOR) with 95% confidence interval (CI). RESULTS: There were 794 patients in the IBD-RSV cohort and 93,074 patients in the non-IBD-RSV cohort. The mean age of the IBD-RSV cohort was 55.6 ± 20 years, 59% were female, 80% were White, and 56.9% had Crohn's disease. The IBD-RSV cohort was at an increased risk of hospitalization (aOR 1.30, 95% CI 1.06-1.59). There was no difference in the risk (aOR 0.83, 95% CI 0.58-1.19) of a composite outcome of hospitalization-related complications between the 2 cohorts. Recent systemic corticosteroid use (<3 months) was associated with an increased risk of hospitalization (aOR 1.86, 95% CI 1.30-2.59) in the IBD-RSV cohort. DISCUSSION: We found that adult patients with IBD and RSV infection are at an increased risk of hospitalization and may benefit from the new RSV vaccine recommended for adults aged 60 years and older.

Changes in Therapy Are Not Associated With Increased Remission in Patients With Crohn's Disease of the Pouch.

INTRODUCTION: There is a paucity of data on the real-world effectiveness of therapies in patients with Crohn's disease of the pouch. METHODS: This was a prospective multicenter study evaluating the primary outcome of remission at 12 months of therapy for Crohn's disease of the pouch. RESULTS: One hundred thirty-four patients were enrolled. Among the 77 patients with symptoms at baseline, 35 (46.7%) achieved remission at 12 months. Of them, 12 (34.3%) changed therapy. There was no significant association between therapy patterns and remission status. DISCUSSION: Approximately 50% with symptoms at enrollment achieved clinical remission at 12 months, most of whom did so without a change in therapy.

Histologic Activity From Neoterminal Ileal Biopsies in Patients With Crohn's Disease in Endoscopic Remission is Associated With Postoperative Recurrence.

INTRODUCTION: Following ileocolic resection (ICR), the clinical importance and prognostic implications of histologic activity on biopsies in Crohn's disease (CD) patients with endoscopic remission are not well defined. The aim of this study was to determine if histologic activity in patients with endoscopic remission is associated with future risk of endoscopic and/or radiologic postoperative recurrence (POR). METHODS: In this multicenter retrospective cohort study, adult patients with CD who underwent ICR between 2009 and 2020 with endoscopic biopsies of ileal mucosa from Rutgeerts i0 on index colonoscopy were included. The composite rate of endoscopic (Rutgeerts score ≥i2b) and radiologic (active inflammation on imaging) recurrence was compared in patients with and without histologic activity using a Kaplan-Meier survival analysis. A multivariable Cox proportional hazard regression model including clinically relevant risk factors of POR, postoperative biologic prophylaxis, and histology activity was designed. RESULTS: A total of 113 patients with i0 disease on index colonoscopy after ICR were included. Of these, 42% had histologic activity. Time to POR was significantly earlier in the histologically active versus normal group ( P = 0.04). After adjusting for clinical risk factors of POR, histologic activity (HR 2.37, 95% CI 1.17-4.79; P = 0.02) and active smoking (HR 2.54, 95% CI 1.02-6.33; P = 0.05) were independently associated with subsequent composite POR risk. DISCUSSION: In patients with postoperative CD, histologic activity despite complete endoscopic remission is associated with composite, endoscopic, and radiographic recurrence. Further understanding of the role of histologic activity in patients with Rutgeerts i0 disease may provide a novel target to reduce disease recurrence in this population.

Factors Associated With Performing IPAA After Total Colectomy for Ulcerative Colitis.

BACKGROUND: IPAA is considered the procedure of choice for restorative surgery after total colectomy for ulcerative colitis. Previous studies have examined the rate of IPAA within individual states but not at the national level in the United States. OBJECTIVE: This study aimed to assess the rate of IPAA after total colectomy for ulcerative colitis in a national population and identify factors associated with IPAA. DESIGN: This was a retrospective cohort study. SETTINGS: This study was performed in the United States. PATIENTS: Patients who were aged 18 years or older and who underwent total colectomy between 2009 and 2019 for a diagnosis of ulcerative colitis were identified within a commercial database. This database excluded patients with public insurance, including all patients older than 65 years with Medicare. MAIN OUTCOME MEASURES: The primary outcome was IPAA. Multivariable logistic regression was used to assess the association between covariates and the likelihood of undergoing IPAA. RESULTS: In total, 2816 patients were included, of whom 1414 (50.2%) underwent IPAA, 928 (33.0%) underwent no further surgery, and 474 (16.8%) underwent proctectomy with end ileostomy. Younger age, lower comorbidities, elective case, and laparoscopic approach in the initial colectomy were significantly associated with IPAA but socioeconomic status was not. LIMITATIONS: This retrospective study included only patients with commercial insurance. CONCLUSIONS: A total of 50.2% of patients who had total colectomy for ulcerative colitis underwent IPAA, and younger age, lower comorbidities, and elective cases are associated with a higher rate of IPAA placement. This study emphasizes the importance of ensuring follow-up with colorectal surgeons to provide the option of restorative surgery, especially for patients undergoing urgent or emergent colectomies. See Video Abstract . FACTORES ASOCIADOS CON LA REALIZACIN DE ANASTOMOSIS ANALBOLSA ILEAL DESPUS DE UNA COLECTOMA TOTAL POR COLITIS ULCEROSA: ANTECEDENTES:La anastomosis ileo-anal se considera el procedimiento de elección para la cirugía reparadora tras la colectomía total por colitis ulcerosa. Estudios previos han examinado la tasa de anastomosis ileo-anal dentro de los estados individuales, pero no a nivel nacional en los Estados Unidos.OBJETIVO:Evaluar la tasa de anastomosis bolsa ileal-anal después de la colectomía total para la colitis ulcerosa en una población nacional e identificar los factores asociados con la anastomosis bolsa ileal-anal.DISEÑO:Se trata de un estudio de cohortes retrospectivo.LUGAR:Este estudio se realizó en los Estados Unidos.PACIENTES:Los pacientes que tenían ≥18 años de edad que se sometieron a colectomía total entre 2009 y 2019 para un diagnóstico de colitis ulcerosa fueron identificados dentro de una base de datos comercial. Esta base de datos excluyó a los pacientes con seguro público, incluidos todos los pacientes >65 años con Medicare.MEDIDAS DE RESULTADO PRINCIPALES:El resultado primario fue la anastomosis ileal bolsa-anal. Se utilizó una regresión logística multivariable para evaluar la asociación entre las covariables y la probabilidad de someterse a una anastomosis ileal.RESULTADOS:En total, se incluyeron 2.816 pacientes, de los cuales 1.414 (50,2%) se sometieron a anastomosis ileo-anal, 928 (33,0%) no se sometieron a ninguna otra intervención quirúrgica y 474 (16,8%) se sometieron a proctectomía con ileostomía terminal. La edad más joven, las comorbilidades más bajas, el caso electivo, y el abordaje laparoscópico en la colectomía inicial se asociaron significativamente con la anastomosis ileal bolsa-anal, pero no el estatus socioeconómico.LIMITACIONES:Este estudio retrospectivo incluyó sólo pacientes con seguro comercial.CONCLUSIONES:Un 50,2% de los pacientes se someten a anastomosis ileo-anal y la edad más joven, las comorbilidades más bajas y los casos electivos se asocian con una mayor tasa de colocación de anastomosis ileo-anal. Esto subraya la importancia de asegurar el seguimiento con cirujanos colorrectales para ofrecer la opción de cirugía reparadora, especialmente en pacientes sometidos a colectomías urgentes o emergentes. (Traducción-Dr. Yolanda Colorado ).

Machine Learning and Health Science Research: Tutorial.

Machine learning (ML) has seen impressive growth in health science research due to its capacity for handling complex data to perform a range of tasks, including unsupervised learning, supervised learning, and reinforcement learning. To aid health science researchers in understanding the strengths and limitations of ML and to facilitate its integration into their studies, we present here a guideline for integrating ML into an analysis through a structured framework, covering steps from framing a research question to study design and analysis techniques for specialized data types.

Increasing Incidence of Pouchitis Between 1996 and 2018: A Population-Based Danish Cohort Study.

BACKGROUND & AIMS: Current knowledge regarding the epidemiology of pouchitis is based on highly selected, mostly single-center, patient cohorts. Our objective was to prospectively determine the population-based incidence of pouchitis in patients with ulcerative colitis in the first 2 years after ileal pouch-anal anastomosis and analyze time trends of the incidence of pouchitis. METHODS: Using national registries, we established a population-based cohort of all Danish patients undergoing proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis between 1996 and 2018. The primary outcome was the development of pouchitis within the first 2 years after surgery, evaluated by time period. We used Kaplan-Meier and Cox proportional hazard modeling to evaluate the time to development of pouchitis. RESULTS: Overall, 1664 patients underwent an ileal pouch-anal anastomosis. The cumulative incidence of pouchitis in the 2 years after ileal pouch-anal anastomosis increased throughout the study period, from 40% in the period from 1996 to 2000 (95% CI, 35%-46%) to 55% in the period from 2015 to 2018 (95% CI, 48%-63%). Patients undergoing surgery between 2015 and 2018 also showed an increased risk of pouchitis compared with the earliest study period (1996-2000) after adjusting for sex, age, and socioeconomic status (hazard ratio, 1.57; 95% CI, 1.20-2.05). CONCLUSIONS: This population-based study showed a 15% absolute and 38% relative increase in the incidence of pouchitis among patients undergoing surgery between 1996 and 2018, with the greatest cumulative incidence of pouchitis shown in the most recent era (2015-2018). The striking increase in the incidence of pouchitis highlights the need for further research into causes and prevention of pouchitis.

Development of the Endoscopic Pouch Score for Assessment of Inflammatory Conditions of the Pouch.

Pouchoscopy provides a critical objective measure in the evaluation of patients with suspected inflammatory conditions of the pouch; however, there remain significant gaps in the reliability of the endoscopic scales used in the assessment of these conditions.1,2 Reliability and reproducibility in the assessment of patients after ileal pouch-anal anastomosis (IPAA) are critical, as evidenced by recent efforts to improve standardization in the evaluation of patients with pouch-related disorders.3.

Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2021.

BACKGROUND & AIMS: Gastrointestinal diseases account for considerable health care use and expenditures. We estimated the annual burden, costs, and research funding associated with gastrointestinal, liver, and pancreatic diseases in the United States. METHODS: We generated estimates using data from the National Ambulatory Medical Care Survey; National Hospital Ambulatory Medical Care Survey; Nationwide Emergency Department Sample; National Inpatient Sample; Kids' Inpatient Database; Nationwide Readmissions Database; Surveillance, Epidemiology, and End Results program; National Vital Statistics System; Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research; MarketScan Commercial Claims and Encounters data; MarketScan Medicare Supplemental data; United Network for Organ Sharing registry; Medical Expenditure Panel Survey; and National Institutes of Health (NIH). RESULTS: Gastrointestinal health care expenditures totaled $119.6 billion in 2018. Annually, there were more than 36.8 million ambulatory visits for gastrointestinal symptoms and 43.4 million ambulatory visits with a primary gastrointestinal diagnosis. Hospitalizations for a principal gastrointestinal diagnosis accounted for more than 3.8 million admissions, with 403,699 readmissions. A total of 22.2 million gastrointestinal endoscopies were performed, and 284,844 new gastrointestinal cancers were diagnosed. Gastrointestinal diseases and cancers caused 255,407 deaths. The NIH supported $3.1 billion (7.5% of the NIH budget) for gastrointestinal research in 2020. CONCLUSIONS: Gastrointestinal diseases are responsible for millions of health care encounters and hundreds of thousands of deaths that annually costs billions of dollars in the United States. To reduce the high burden of gastrointestinal diseases, focused clinical and public health efforts, supported by additional research funding, are warranted.

Comparative Safety of Biologic Agents in Patients With Inflammatory Bowel Disease With Active or Recent Malignancy: A Multi-Center Cohort Study.

BACKGROUND & AIMS: Safety of biologic agents is a key consideration in patients with inflammatory bowel disease (IBD) and active or recent cancer. We compared the safety of tumor necrosis factor (TNF)-α antagonists vs non-TNF biologics in patients with IBD with active or recent cancer. METHODS: We conducted a multicenter retrospective cohort study of patients with IBD and either active cancer (cohort A) or recent prior cancer (within ≤5 years; cohort B) who were treated with TNFα antagonists or non-TNF biologics after their cancer diagnosis. Primary outcomes were progression-free survival (cohort A) or recurrence-free survival (cohort B). Safety was compared using inverse probability of treatment weighting with propensity scores. RESULTS: In cohort A, of 125 patients (483.8 person-years of follow-up evaluation) with active cancer (age, 54 ± 15 y, 75% solid-organ malignancy), 10 of 55 (incidence rate [IR] per 100 py, 4.4) and 9 of 40 (IR, 10.4) patients treated with TNFα antagonists and non-TNF biologics had cancer progression, respectively. There was no difference in the risk of progression-free survival between TNFα antagonists vs non-TNF biologics (hazard ratio, 0.76; 95% CI, 0.25-2.30). In cohort B, of 170 patients (513 person-years of follow-up evaluation) with recent prior cancer (age, 53 ± 15 y, 84% solid-organ malignancy; duration of remission, 19 ± 19 mo), 8 of 78 (IR, 3.4) and 5 of 66 (IR 3.7) patients treated with TNFα antagonists and non-TNF biologics had cancer recurrence, respectively. The risk of recurrence-free survival was similar between both groups (hazard ratio, 0.94; 95% CI, 0.24-3.77). CONCLUSIONS: In patients with IBD with active or recent cancer, TNFα antagonists and non-TNF biologics have comparable safety. The choice of biologic should be dictated by IBD disease severity in collaboration with an oncologist.

Classification and Management of Disorders of the J Pouch.

Total abdominal proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) is associated with substantial complications despite the benefits of managing refractory and/or neoplasia-associated disease. For the purpose of this review, we focused on the diagnosis of some of the most common inflammatory and structural pouch disorders and their respective management. Pouchitis is the most common complication, and it is typically responsive to antibiotics. However, chronic antibiotic refractory pouchitis (CARP) has been increasingly recognized, and biologic therapies have emerged as the mainstay of therapy. Crohn's-like disease of the pouch (CLDP) can affect up to 10% of patients with UC after IPAA. Medical options are similar to CARP therapies, including biologics with immunomodulators. Studies have shown higher efficacy rates of biologics for CLDP when compared with those for CARP. In addition, managing stricturing and fistulizing CLDP is challenging and often requires interventional endoscopy (balloon dilation and/or stricturotomy) and/or surgery. The implementation of standardized diagnostic criteria for inflammatory pouch disorders will help in advancing future therapeutic options. Structural pouch disorders are commonly related to surgical complications after IPAA. We focused on the diagnosis and management of anastomotic leaks, strictures, and floppy pouch complex. Anastomotic leaks and anastomotic strictures occur in approximately 15% and 11% of patients with UC after IPAA, respectively. Further complications from pouch leaks include the development of sinuses, fistulas, and pouch sepsis requiring excision. Novel endoscopic interventions and less invasive surgical procedures have emerged as options for the management of these disorders.

The Comparative Effectiveness of Ciprofloxacin and Metronidazole for an Initial Episode of Pouchitis: A Propensity-Matched Study.

INTRODUCTION: There is minimal evidence regarding the comparative effectiveness of individual antibiotics in the treatment of pouchitis. We sought to evaluate the comparative effectiveness of ciprofloxacin monotherapy, metronidazole monotherapy, and combination therapy (ciprofloxacin and metronidazole) in the treatment of an initial episode of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis (UC). METHODS: We performed a retrospective cohort study in TriNetX, a global federated research network of electronic health records. Primary outcomes were failure of initial antibiotic therapy and the development of recurrent pouchitis in the first 12 months after an initial episode of pouchitis. One-to-one propensity score matching was performed for age, sex, race, primary sclerosing cholangitis, nicotine dependence, obesity, and previous exposure to tumor necrosis factor inhibitors between the cohorts. RESULTS: Among 271 patients who developed pouchitis (mean age at ileal pouch-anal anastomosis 35.8 years, male sex 57%) and were treated with ciprofloxacin, metronidazole, or combination therapy, 190 (70%) developed recurrent pouchitis. After propensity score matching, there was no significant difference in the odds of early relapse or nonresponse with ciprofloxacin compared with metronidazole monotherapy (adjusted odds ratio 0.56, 95% confidence interval 0.23-1.34) or when either monotherapy was compared with combination therapy. There was also no significant difference in odds of recurrent pouchitis when comparing patients treated with ciprofloxacin with metronidazole monotherapy (adjusted odds ratio 0.86, 95% confidence interval 0.40-1.84) or either monotherapy with combination therapy. DISCUSSION: In this retrospective cohort study, we demonstrated no significant difference in the real-world effectiveness of ciprofloxacin, metronidazole, or combination therapy for the initial episode of pouchitis.

Rate of Colectomy Increases Within 12 Months of Sequential Therapy for Ulcerative Colitis.

INTRODUCTION: Patients with medically refractory ulcerative colitis who previously would have undergone surgery can now elect for subsequent medical therapy. METHODS: In a commercially insured population, we evaluated the proportion of patients initiating second-line, third-line, or fourth-line treatment who underwent colectomy in the following 12 months. RESULTS: Among 3,325 patients with ulcerative colitis, the colectomy rate within 12 months of a switch in therapy increased from 12% with the first switch to 17% and 19% with the second and third switches, respectively ( P < 0.001). DISCUSSION: Treatment effectiveness declines with successive switching; however, even after initiating fourth-line therapy, most patients remain surgery-free.

Anastomotic Configuration and Temporary Diverting Ileostomy Do Not Increase Risk of Anastomotic Stricture in Postoperative Crohn's Disease.

INTRODUCTION: Surgical management of Crohn's disease (CD) is common. Postoperative complications include anastomotic stricturing (AS). The natural history and risk factors for AS have not been elucidated. METHODS: A retrospective cohort study of patients with CD who underwent ileocolonic resection (ICR) with ≥1 postoperative ileocolonoscopy between 2009 and 2020. Postoperative ileocolonoscopies with corresponding cross-sectional imaging were evaluated for evidence of AS without neoterminal ileal extension. Severity of AS and endoscopic intervention at time of detection were collected. Primary outcome was development of AS. Secondary outcome was time to AS detection. RESULTS: A total of 602 adult patients with CD underwent ICR with postoperative ileocolonoscopy. Of these, 426 had primary anastomosis, and 136 had temporary diversion at time of ICR. Anastomotic configuration consisted of 308 side-to-side, 148 end-to-side, and 136 end-to-end. One hundred ten (18.3%) patients developed AS with median time of 3.2 years to AS detection. AS severity at time of detection was associated with need for repeat surgical resection for AS. On multivariable Cox proportional hazard regression, anastomotic configuration and temporary diversion were not associated with risk of or time to AS. Preoperative stricturing disease was associated with decreased time to AS (adjusted hazard ratio 1.8; P = 0.049). Endoscopic ileal recurrence before AS was not associated with subsequent AS detection. DISCUSSION: AS is a relatively common postoperative CD complication. Patients with previous stricturing disease behavior are at increased risk of AS. Anastomotic configuration, temporary diversion, and ileal CD recurrence do not increase risk of AS. Early detection and intervention for AS may help prevent progression to repeat ICR.

Change in Biologic Class Promotes Endoscopic Remission Following Endoscopic Postoperative Crohn's Disease Recurrence.

GOALS: Assess the outcomes of various therapeutic regimens to treat initial endoscopic postoperative recurrence despite biologic prophylaxis. BACKGROUND: Postoperative biologic prophylaxis reduces postoperative Crohn's disease (CD) recurrence rates. Optimal treatment strategies for endoscopic recurrence have not been elucidated. STUDY: Retrospective cohort study of adult CD patients who underwent ileocolonic resection between 2009 and 2020. Patients with endoscopic postoperative recurrence despite prophylactic biologic therapy and ≥1 subsequent colonoscopy were included. Treatment changes after recurrence were categorized as (1) therapy optimization or continuation or (2) new biologic class. The primary outcome was composite endoscopic or surgical recurrence at the time of or prior to subsequent follow-up colonoscopy. RESULTS: Eighty-one CD patients with endoscopic recurrence (54.3% i2b, 22.2% i3, and 23.5% i4) despite biologic prophylaxis (86.4% anti-tumor necrosis factor, 8.6% vedolizumab, 4.9% ustekinumab) were included. Most patients received therapy optimization or continuation (76.3%, n=61) following recurrence compared to being started on a new biologic class. Sixty patients (N=48 therapy optimization; N=12 new biologic class) experienced composite recurrence (78.3% endoscopic, 21.7% surgical). On multivariable modeling, initiation of a new biologic class was associated with reduced risk for composite recurrence compared to therapy optimization or continuation (aOR: 0.26; P=0.04). Additionally, initiation of a new biologic class was associated with endoscopic improvement when adjusting for endoscopic severity at the time of recurrence (aOR: 3.4; P=0.05). On sensitivity analysis, a new biologic class was associated or trended with improved rates of endoscopic healing and composite recurrence when directly compared to therapy optimization or continuation. CONCLUSION: In patients with CD who experience endoscopic recurrence despite biologic prophylaxis, changing the mechanism of biologic action may promote endoscopic improvement.