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.

Comparative Effectiveness of Anti-TNF in Combination With Low-Dose Methotrexate vs Anti-TNF Monotherapy in Pediatric Crohn's Disease: A Pragmatic Randomized Trial.

BACKGROUND & AIMS: Tumor necrosis factor inhibitors, including infliximab and adalimumab, are a mainstay of pediatric Crohn's disease therapy; however, nonresponse and loss of response are common. As combination therapy with methotrexate may improve response, we performed a multicenter, randomized, double-blind, placebo-controlled pragmatic trial to compare tumor necrosis factor inhibitors with oral methotrexate to tumor necrosis factor inhibitor monotherapy. METHODS: Patients with pediatric Crohn's disease initiating infliximab or adalimumab were randomized in 1:1 allocation to methotrexate or placebo and followed for 12-36 months. The primary outcome was a composite indicator of treatment failure. Secondary outcomes included anti-drug antibodies and patient-reported outcomes of pain interference and fatigue. Adverse events (AEs) and serious AEs (SAEs) were collected. RESULTS: Of 297 participants (mean age, 13.9 years, 35% were female), 156 were assigned to methotrexate (110 infliximab initiators and 46 adalimumab initiators) and 141 to placebo (102 infliximab initiators and 39 adalimumab initiators). In the overall population, time to treatment failure did not differ by study arm (hazard ratio, 0.69; 95% CI, 0.45-1.05). Among infliximab initiators, there were no differences between combination and monotherapy (hazard ratio, 0.93; 95% CI, 0.55-1.56). Among adalimumab initiators, combination therapy was associated with longer time to treatment failure (hazard ratio, 0.40; 95% CI, 0.19-0.81). A trend toward lower anti-drug antibody development in the combination therapy arm was not significant (infliximab: odds ratio, 0.72; 95% CI, 0.49-1.07; adalimumab: odds ratio, 0.71; 95% CI, 0.24-2.07). No differences in patient-reported outcomes were observed. Combination therapy resulted in more AEs but fewer SAEs. CONCLUSIONS: Among adalimumab but not infliximab initiators, patients with pediatric Crohn's disease treated with methotrexate combination therapy experienced a 2-fold reduction in treatment failure with a tolerable safety profile. CLINICALTRIALS: gov, Number: NCT02772965.

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.

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.

HLA DQA1*05 and risk of anti-TNF treatment failure and anti-drug antibody development in children with Crohn's Disease: HLA DQA1*05 and Pediatric Crohn's Disease.

OBJECTIVES: HLA DQA1*05 has been associated with the development of anti-drug antibodies (ADA) to tumor necrosis factor antagonists (anti-TNF) and treatment failure among adults with Crohn's disease (CD). However, findings from other studies have been inconsistent with limited pediatric data. METHODS: We analyzed banked serum from patients with CD < 21 years of age enrolled in COMBINE, a multi-center, prospective randomized trial of anti-TNF monotherapy vs. combination with methotrexate. The primary outcome was a composite of factors indicative of treatment failure. The secondary outcome was ADA development. RESULTS: A trend towards increased treatment failure among HLA DQA1*05 positive participants was not significant (HR 1.58, 95% CI 0.95-2.62; p=0.08). After stratification by HLA DQA1*05 and by methotrexate vs. placebo, patients who were HLA DQA1*05 negative and assigned to methotrexate experienced less treatment failures than HLA DQA1*05 positive patients on placebo (HR 0.31, 95% CI 0.13-0.70; p=0.005).A trend toward increased ADA development among HLA DQA1*05 positive participants was not significant (odds ratio [OR] 1.96, 95% CI 0.90-4.31, p=0.09). After further stratification, HLA DQA1*05 negative participants assigned to methotrexate were less likely to develop ADA relative to HLA DQA1*05 positive patients on placebo (OR 0.12, 95% CI 0.03-0.55; p=0.008). CONCLUSIONS: In a randomized trial of children with CD initiating anti-TNF, 40% were HLA DQ-A1*05 positive, which was associated with a trend toward increased risk of both treatment failure and ADA. These risks were mitigated, but not eliminated, by adding oral methotrexate. HLA DQ-A1*05 is an important biomarker for prognosis and risk stratification.

High Body Mass Index and Response to Anti-Tumor Necrosis Factor Therapy in Pediatric Crohn's Disease.

INTRODUCTION: Obesity is common among patients with pediatric Crohn's disease (PCD). Some adult studies suggest obese patients respond less well to anti-tumor necrosis factor (TNF) treatment. This study sought compares anti-TNF response and anti-TNF levels between pediatric patients with normal and high body mass index (BMI). METHODS: The COMBINE trial compared anti-TNF monotherapy with combination therapy with methotrexate in patients with PCD. In this secondary analysis, a comparison of time-to-treatment failure among patients with normal BMI vs BMI Z -score >1, adjusting for prescribed anti-TNF (infliximab [IFX] or adalimumab [ADA]), trial treatment assignment (combination vs monotherapy), and relevant covariates. Median anti-TNF levels across BMI category was also examined. RESULTS: Of 224 participants (162 IFX initiators and 62 ADA initiators), 111 (81%) had a normal BMI and 43 (19%) had a high BMI. High BMI was associated with treatment failure among ADA initiators (7/10 [70%] vs 12/52 [23%], hazard ratio 0.29, P = 0.007) but not IFX initiators. In addition, ADA-treated patients with a high BMI had lower ADA levels compared with those with normal BMI (median 5.8 vs 12.8 µg/mL, P = 0.02). IFX trough levels did not differ between BMI groups. DISCUSSION: Overweight and obese patients with PCD are more likely to experience ADA treatment failure than those with normal BMI. Higher BMI was associated with lower drug trough levels. Standard ADA dosing may be insufficient for overweight children with PCD. Among IFX initiators, there was no observed difference in clinical outcomes or drug levels, perhaps due to weight-based dosing and/or greater use of proactive drug monitoring.

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 ).

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.

Prospective Cohort Study to Investigate the Safety of Preoperative Tumor Necrosis Factor Inhibitor Exposure in Patients With Inflammatory Bowel Disease Undergoing Intra-abdominal Surgery.

BACKGROUND & AIMS: Whether preoperative treatment of inflammatory bowel disease (IBD) with tumor necrosis factor inhibitors (TNFis) increases the risk of postoperative infectious complications remains controversial. The primary aim of this study was to determine whether preoperative exposure to TNFis is an independent risk factor for postoperative infectious complications within 30 days of surgery. METHODS: We conducted a multicenter prospective observational study of patients with IBD undergoing intra-abdominal surgery across 17 sites from the Crohn's & Colitis Foundation Clinical Research Alliance. Infectious complications were categorized as surgical site infections (SSIs) or non-SSIs. Current TNFi exposure was defined as use within 12 weeks of surgery, and serum was collected for drug-level analyses. Multivariable models for occurrence of the primary outcome, any infection, or SSI were adjusted by predefined covariates (age, sex, preoperative steroid use, and disease type), baseline variables significantly associated (P < .05) with any infection or SSI separately, and TNFi exposure status. Exploratory models used TNFi exposure based on serum drug concentration. RESULTS: A total of 947 patients were enrolled from September 2014 through June 2017. Current TNFi exposure was reported by 382 patients. Any infection (18.1% vs 20.2%, P = .469) and SSI (12.0% vs 12.6%, P = .889) rates were similar in patients currently exposed to TNFis and those unexposed. In multivariable analysis, current TNFi exposure was not associated with any infection (odds ratio, 1.050; 95% confidence interval, 0.716-1.535) or SSI (odds ratio, 1.249; 95% confidence interval, 0.793-1.960). Detectable TNFi drug concentration was not associated with any infection or SSI. CONCLUSIONS: Preoperative TNFi exposure was not associated with postoperative infectious complications in a large prospective multicenter cohort.

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.

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

INTRODUCTION: Chronic inflammatory conditions of the pouch are common after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). AIMS: We aimed to investigate the relationship between acute pouchitis within 180 days 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). METHODS: 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. RESULTS: 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 5.18 years (interquartile range 0.94-10.8 years). 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). CONCLUSION: 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.

Patients With Pouchitis Demonstrate a Significant Cost Burden in the First Two Years After Ileal Pouch-Anal Anastomosis.

Pouchitis, the most common long-term complication after colectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), can lead to increased health care costs and diminished quality of life.1 In this study, we aimed to compare the total costs among patients diagnosed with pouchitis in the first 2 years after an IPAA with those among patients who were not diagnosed with pouchitis, using a large administrative claims database. Additionally, we aimed to investigate the specific drivers of cost among patients with an IPAA during the 2-year study period, including inpatient hospitalizations, emergency department visits, and pharmacy-related costs.

A Randomized Trial Comparing the Specific Carbohydrate Diet to a Mediterranean Diet in Adults With Crohn's Disease.

BACKGROUND & AIMS: This study compared the effectiveness of the Specific Carbohydrate Diet (SCD) to the Mediterranean diet (MD) as treatment for Crohn's disease (CD) with mild to moderate symptoms. METHODS: Adult patients with CD and with mild-to-moderate symptoms were randomly assigned 1:1 to consume the MD or SCD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks according to their assigned diet. After 6 weeks, participants were instructed to follow the diet independently. The primary outcome was symptomatic remission at week 6. Key secondary outcomes at week 6 included fecal calprotectin (FC) response (FC <250 µg/g and reduction by >50% among those with baseline FC >250 µg/g) and C-reactive protein (CRP) response (high-sensitivity CRP <5 mg/L and >50% reduction from baseline among those with high-sensitivity CRP >5 mg/L). RESULTS: The study randomized 194 patients, and 191 were included in the efficacy analyses. The percentage of participants who achieved symptomatic remission at week 6 was not superior with the SCD (SCD, 46.5%; MD, 43.5%; P = .77). FC response was achieved in 8 of 23 participants (34.8%) with the SCD and in 4 of 13 participants (30.8%) with the MD (P = .83). CRP response was achieved in 2 of 37 participants (5.4%) with the SCD and in 1 of 28 participants (3.6%) with the MD (P = .68). CONCLUSIONS: The SCD was not superior to the MD to achieve symptomatic remission, FC response, and CRP response. CRP response was uncommon. Given these results, the greater ease of following the MD and other health benefits associated with the MD, the MD may be preferred to the SCD for most patients with CD with mild to moderate symptoms. ClinicalTrials.gov Identifier: NCT03058679.

Same Day Infusion of Iron Therapy Is Associated With No Increased Risk for Adverse Events Among Patients Receiving Biological Infusions for Inflammatory Bowel Disease.

GOALS: The goal of this study was to compare the relative safety of administering iron infusions on the same day as intravenous (IV) biological therapy to the administration of these treatments on different days in patients with inflammatory bowel disease (IBD). BACKGROUND: IV iron therapy is often required in patients with IBD. Many patients with IBD who receive IV iron therapy in the outpatient setting also receive biological infusion therapy for treatment of their IBD. STUDY: Patients with IBD who received IV iron therapy at a single infusion center were included. We compared documented infusion-related reactions in patients with patients receiving an iron infusion on the same day as their biological infusion to those who received their iron infusion on a different day. RESULTS: Among 481 patients, 129 received an iron infusion on the same day as a biologic infusion. There was no significant difference in the incidence of infusion reaction when comparing patients who received biological infusion therapy in the same session as the iron infusion to those patients who received a biological infusion on a different day (5% vs. 7%, P =0.246) or any IBD-related therapy (5% vs. 8%, P =0.206). CONCLUSIONS: The frequency and type of infusion reactions in patients receiving IV iron therapy on the same day after IV therapy with biologics was not increased compared with patients who received a biological infusion on a different day. A sequential infusion of biological therapy followed by IV iron therapy may be a safe and cost-effective approach.

Disease Monitoring of the Ileoanal Pouch: How to Utilize Biomarkers, Imaging, and Pouchoscopy.

PURPOSE OF REVIEW: Restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis has been associated with multiple short- and long-term complications. In this review, we examine the role of biomarkers, imaging, and pouchoscopy in the assessment of patients after ileal pouch-anal anastomosis, with a particular focus on the emergence of novel biomarkers and techniques for evaluating and risk stratifying patients after this procedure in the hopes of improving outcomes in this specific population. RECENT FINDINGS: There are indications that that the incidence of pouchitis may be increasing in recent decades. Calprotectin and other non-invasive imaging tests such as ultrasound may offer advantages in distinguishing patients with inflammatory conditions of the pouch from other etiologies. In the search for other biomarkers that may identify patients at risk for inflammatory conditions of the pouch, the stool microbiota and metabolomics may play a key role in identifying those patients at greatest risk for complications. Advances in biomarkers, imaging, and standardized pouchoscopy scoring offer immediate improvements in clinical care and will prompt future research efforts.

Relationship Between Stages of Ileal Pouch-Anal Anastomosis, Timing of Restoration of Fecal Continuity, and Pouchitis.

BACKGROUND: The most common complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is pouchitis. AIMS: We aimed to investigate whether a shorter period between pouch creation and restoration of fecal flow through an IPAA was associated with an increased risk of development of pouchitis within the first 2 years after IPAA. METHODS: We performed a retrospective cohort study evaluating patients undergoing colectomy with IPAA for UC between January 1, 2004 and December 31, 2016. We used Kaplan-Meier testing and Cox Proportional Hazards Modeling to evaluate the relationship between the time between restoration of fecal continuity and time to subsequent development of pouchitis, adjusting for other clinical and demographic factors. RESULTS: We identified 624 patients who underwent proctocolectomy with IPAA for UC, of whom 246 (39%) developed pouchitis within the first 2 years after IPAA. There was no difference when comparing the median time to restoration of continuity among those patients who developed pouchitis and those who did not (49 days vs. 49 days, p = 0.85) or in multivariable analysis. Primary sclerosing cholangitis (Hazard Ratio [HR] 2.14, 95% CI 1.12-4.08), family history of inflammatory bowel disease (HR 1.49, 95% CI 1.08-2.06), and delayed pouch creation (HR 0.75, 95% CI 0.57-1.00) were significantly associated with time to development of pouchitis. CONCLUSION: Although a staged approach to IPAA may have benefits in the surgical management of UC, the timing interval between pouch creation and restoration of continuity did not impact the subsequent development of early pouchitis in this cohort.

Incidence, Risk Factors, and Outcomes of Pouchitis and Pouch-Related Complications in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Acute pouchitis is the most common non-surgical complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). We used validated case-finding definitions for pouchitis to search administrative claims data and determine the incidence of pouchitis in the first 2 years after IPAA. METHODS: We identified all patients who underwent proctocolectomy with IPAA for UC in the IQVIA Legacy PharMetrics Adjudicated Claims Database, from January 1, 2007 through June 1, 2016. The primary outcome was the development of pouchitis within 2 years after IPAA. Secondary outcomes included isolated acute vs recurrent pouchitis, immunosuppressive therapy, further surgery, and admission to the hospital. RESULTS: Among 594 patients, the cumulative incidence of pouchitis within 2 years of IPAA was 48% (95% CI, 44%-52%). The cumulative incidence of isolated acute pouchitis was 29% (95% CI, 26%-33%). Compared to patients with isolated acute pouchitis, patients who received a diagnosis of recurrent pouchitis (cumulative incidence, 19%: 95% CI, 16%-22%) demonstrated increased outpatient visits, emergency department visits, and inpatient admissions (all P < .001). Patients who developed pouchitis were more likely to have a history of primary sclerosing cholangitis (adjusted odds ratio [aOR], 3.94; 95% CI, 1.05-14.8) and anti-tumor necrosis factor alpha therapy prior to colectomy (aOR 1.63; 95% CI, 1.09-2.45). Among patients with pouchitis, the cumulative frequency of new immunosuppressive therapy was 40% (95% CI, 35%-46%) and the cumulative incidence of pouch excision was 1.0% (95% CI, 0.4%-3.0%). The cumulative incidence of a new diagnosis of Crohn's disease after IPAA for UC was 9.0% (95% CI, 7.2%-11%). CONCLUSIONS: In a geographically diverse population, 48% of patients with UC developed pouchitis within the first 2 years after IPAA. Patients with pouchitis had greater use of healthcare resources, indicating a significant burden of disease.

Creation of a Case-Finding Definition for Identifying Patients With Acute Pouchitis in Administrative Claims Data.

Acute pouchitis is the most common complication after a restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, affecting 40% of patients within the first year after surgery.1 Although up to 80% of patients can develop pouchitis symptoms,2,3 substantial gaps remain in our understanding of the epidemiology and burden of pouchitis. Administrative claims have been used to advance the knowledge of other areas of inflammatory bowel disease4-6; however, a prerequisite to conducting such studies in pouchitis is a valid, reliable case-finding algorithm. Given concerns that the International Classification of Diseases (ICD) code for pouchitis may not be reliably used by clinicians (resulting in a low sensitivity), the objectives of the study were to (1) develop a series of case-finding definitions for acute pouchitis and (2) compare the performance of these case-finding definitions to that of a single ICD code for pouchitis.

Efficacy and Safety of Upadacitinib in a Randomized Trial of Patients With Crohn's Disease.

BACKGROUND & AIMS: We evaluated the efficacy and safety of upadacitinib, an oral selective Janus kinase 1 inhibitor, in a randomized trial of patients with Crohn's disease (CD). METHODS: We performed a double-blind, phase 2 trial in adults with moderate to severe CD and inadequate response or intolerance to immunosuppressants or tumor necrosis factor antagonists. Patients were randomly assigned (1:1:1:1:1:1) to groups given placebo; or 3 mg, 6 mg, 12 mg, or 24 mg upadacitinib twice daily; or 24 mg upadacitinib once daily and were evaluated by ileocolonoscopy at weeks 12 or 16 of the induction period. Patients who completed week 16 were re-randomized to a 36-week period of maintenance therapy with upadacitinib. The primary endpoints were clinical remission at week 16 and endoscopic remission at week 12 or 16 using the multiple comparison procedure and modeling and the Cochran-Mantel-Haenszel test, with a 2-sided level of 10%. RESULTS: Among the 220 patients in the study, clinical remission was achieved by 13% of patients receiving 3 mg upadacitinib, 27% of patients receiving 6 mg upadacitinib (P < .1 vs placebo), 11% of patients receiving 12 mg upadacitinib, and 22% of patients receiving 24 mg upadacitinib twice daily, and by 14% of patients receiving 24 mg upadacitinib once daily, vs 11% of patients receiving placebo. Endoscopic remission was achieved by 10% (P < .1 vs placebo), 8%, 8% (P < .1 vs placebo), 22% (P < .01 vs placebo), and 14% (P < .05 vs placebo) of patients receiving upadacitinib, respectively, vs none of the patients receiving placebo. Endoscopic but not clinical remission increased with dose during the induction period. Efficacy was maintained for most endpoints through week 52. During the induction period, patients in the upadacitinib groups had higher incidences of infections and serious infections vs placebo. Patients in the twice-daily 12 mg and 24 mg upadacitinib groups had significant increases in total, high-density lipoprotein, and low-density lipoprotein cholesterol levels compared with patients in the placebo group. CONCLUSIONS: In a phase 2 trial of patients with CD, upadacitinib induced endoscopic remission in a significant proportion of patients compared with placebo. Upadacitinib's benefit/risk profile supports further development for treatment of CD. (Clinicaltrials.gov, Number: NCT02365649).