Faculty Bibliography

Background: Ustekinumab has been recently approved for the treatment of moderately to severely active ulcerative colitis (UC). The registry trials for ustekinumab in UC demonstrated efficacy and safety, but data on real-world outcomes are limited. We describe the effectiveness and safety of ustekinumab in patients with UC from 2 US tertiary inflammatory bowel disease centers. Methods: Patients with moderately to severely active UC treated with ustekinumab at NYU Langone Health (New York, New York) and University of Chicago Medical Center (Chicago, Illinois) between January 2016 and March 2020 were retrospectively included. The primary outcome was clinical remission at 3 and 12 months, defined as a partial Mayo score of ≤2, with a combined rectal bleeding and stool frequency subscore of ≤1. Results: Sixty-six UC patients were included. Ninety-two percent of patients had prior exposure to biologics or tofacitinib. Forty-three percent and 45% of patients achieved clinical remission by 3 and 12 months, respectively. Anti-TNF nonresponse and endoscopic Mayo score of 3 were negative predictors of clinical remission. Thirty-three percent of those followed for a year achieved concurrent endoscopic and histologic healing, which was significantly associated with lower partial Mayo score (P < 0.01) and lower stool frequency (P = 0.02). Serious adverse events occurred in 4 (6%) patients (3 UC exacerbations, 1 vasculitis). Conclusions: In this cohort of mostly biologic-refractory UC patients, treatment with ustekinumab achieved remission in nearly half of them at 12 months, and was associated with an overall favorable safety profile. These results are modestly better than the pivotal trials.

The inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), are chronic, progressive, inflammatory conditions of the gastrointestinal tract. Imbalance in the gut microbial community, or dysbiosis, and the subsequent immune response, represent the critical relationship between genetic susceptibility, microbes, and environment factors, that result in IBD. Gastrointestinal pathogens - a common cause of dysbiosis - have been implicated as an environmental trigger in new onset IBD, as well as flare of existing IBD. In this article, we systematically review clinical data regarding the association between specific gastrointestinal pathogens and IBD. Numerous bacteria, viruses, fungi, and parasites have been implicated in the pathogenesis of IBD, and exacerbations of existing disease. In this article, we will also specifically discuss the less recognized microbes that have an inverse association with IBD, including certain bacterial pathogens, such as Helicobacter pylori, and parasites, such as Trichuris species. Future prospective and experimental studies are required to establish causality and clarify potential mechanisms of enteric pathogens in modifying the risk and course of IBD.

Background: This study evaluated the prevalence of adjunctive pharmacotherapies use among ileal pouch-anal anastomosis (IPAA) patients. Methods: The IBD Partners database was queried to compare IPAA patients with and without pouch-related symptoms (PRS). Within the cohort of patients with PRS, patient reported outcomes were compared among opioid, nonsteroidal anti-inflammatory drug (NSAID), and probiotic users. Results: There were no differences in patient reported outcomes based on NSAID or probiotic usage. Opioid users reported increased bowel frequency, urgency, poor general well-being, abdominal pain, and depression (P < 0.05 for all variables). Conclusions: In IPAA patients with PRS, opioid use, but not NSAIDs or probiotics, was associated with a higher burden of PRS.

INTRODUCTION: Hospitalization for flare of inflammatory bowel disease (IBD) is associated with significant morbidity and healthcare costs. We aimed to examine the relationship between IBD severity at presentation and adverse outcomes in patients hospitalized with flare. Additionally, we aimed to create and validate a predictive model for length of stay (LOS) using markers of disease severity.
METHOD(S): We conducted a retrospective cohort study of IBD patients hospitalized with flare at two urban academic medical centers. We collected demographic and IBD-related data including the presence of Clostridioides difficile and markers of disease severity at presentation. The primary outcome was a composite of adverse inpatient IBD outcomes, including LOS >7 days, anti-TNF administration, and surgery. The data was split into training (70%) and validation (30%) samples. Employing variables of disease severity, models (including logistic regression, Classification and Regression Tree (CART), and Random Forest (RF) modeling techniques) were created to predict LOS >7 days using the training sample. These models were adjusted for surgery and anti-TNF administration, and their performance was subsequently validated.
RESULT(S): A total of 187 IBD patients hospitalized with flare were included (Table 1). The composite primary outcome was achieved in 71 patients (38%) with 51 (27%) hospitalized for >7 days. In univariate analyses, C-reactive protein and C. difficile positivity correlated with anti-TNF administration and surgery (Table 2). Adjusting for anti-TNF administration and surgery, tachycardia (OR 1.07; 95% CI 1.05-1.10), hypotension (1.07; 1.03-1.11), hypoalbuminemia (2.87; 1.81-4.74), leukocytosis (1.17; 1.09-1.27), anemia (1.10; 1.05-1.15) and C. difficile posi-tivity (2.63; 1.27-5.47) were predictive of prolonged LOS (Table 2). In multivariate analyses, tachycardia predicted the primary composite outcome of all adverse effects (OR 1.07; 95% CI 1.03-1.11). C. difficile positivity (OR 4.33; 95% CI 1.36-14.9), hypoalbuminemia (3.25; 1.29-9.01), and tachycardia (1.11; 1.06-1.16) predicted prolonged LOS (.7 days). The CART and RF models had acceptable accuracy, sensitivity, and specificity for predicting LOS >7 days (Table 3).
CONCLUSION(S): C. difficile positivity, hypoalbuminemia, and tachycardia at presentation predicted prolonged length of stay in a multicenter cohort of IBD patients hospitalized with flare. CART and Random Forest models perform well in predicting prolonged length of stay in these patients

INTRODUCTION: Current guidelines recommend preoperative risk stratification to guide postoperative prophylactic biologic therapy for the prevention of Crohn's disease (CD) recurrence1. Few data have corroborated the quantified risk of postoperative recurrence (POR) and validated the proposed risk stratification. We aimed to assess the impact of biologic therapy on POR based on guideline-recommended risk stratification.
METHOD(S): CD patients who underwent an ileocolic resection from 1992-2019 were identified at two tertiary referral centers. Patients were stratified into cohorts with high-risk features (smoking, age < 30 years, and >=2 prior surgeries) and low-risk features (nonsmokers, age >50 years, resection length < 10 cm, and disease duration < 10 years). POR, defined as endoscopic (Rutgeerts . i1) or radiographic evidence of disease at least >6 months after surgery, was compared between groups. Recurrence-free survival analysis using Cox proportional hazard modeling and Kaplan-Meier curves were used to estimate POR and the impact of biologic prophylaxis.
RESULT(S): A total of 950 patients with ileocolic resection for CD were included (mean age 37.9, 47%): 785 (82.6%) high-risk and 165 (17.4%) low-risk patients. In the high-risk group, the majority (58.2%) received biologic prophylaxis (43.4% anti-TNF, 7.1% vedolizumab, and 7.8% ustekinumab) while 41.8% had no therapy. In contrast, 60% of low-risk patients had no therapy while 40% received biologic prophylaxis (32.7% anti-TNF, 8% vedolizumab, and 2.4% ustekinumab). In the high-risk group, biologic prophylaxis was significantly associated with earlier POR compared to no therapy (P < 0.001). In the low-risk group, there was no significant difference between biologic and no therapy in time to POR (P = 0.10; Figure 1). When assessing specific risk factors on multivariable analysis, >=2 prior surgeries was the only independent risk factor for POR (P < 0.05) (Table 1).
CONCLUSION(S): The risk stratification proposed for POR in current guidelines may have limited utility in predicting disease recurrence. Low-risk individuals are unlikely to benefit from postoperative biologic prophylaxis. Multiple prior surgeries is the strongest risk factor for POR and these patients may benefit from postoperative biologic prophylaxis

INTRODUCTION: The outbreak of novel severe acute respiratory virus syndrome coronavirus 2 (SARS-CoV 2), the causative virus of coronavirus disease 2019 (COVID-19), has become a global pandemic. In the United States, cases exceed 2 million, with the New York City (NYC) metropolitan area at the epicenter. Patients with inflammatory bowel disease (IBD) are generally considered higher risk of infection due to immunosuppressive therapies, however, data are lacking regarding outcomes of COVID-19 in patients with IBD compared to the general population. We aim to investigate the impact of IBD on COVID-19 outcomes.
METHOD(S): We prospectively collected data on all patients with IBD [Crohn's disease (CD), ulcerative colitis (UC)] with confirmed or highly suspected COVID-19 (fever and/or close contact plus respiratory symptoms) and all non-IBD patients with confirmed COVID-19 from March 3 to May 10, 2020 at an academic medical center in NYC. Patient demographics, co-morbidities, and medication history were recorded. The endpoints were severe outcomes of COVID-19, including hospitalization, ventilator requirement, ICU admission and death. Adjusted analyses were performed for predictors of a composite endpoint of ventilator, ICU and death.
RESULT(S): We identified 83 patients with IBD [CD (n = 56, 67%) or UC (n = 27, 33%)] with confirmed or suspected COVID-19 and 8277 non-IBD patients with confirmed COVID-19 (Table 1). IBD patients had a lower median age (34 vs. 53 years; P < 0.001) and a higher proportion of Caucasians (69% vs. 41%; P < 0.001). IBD patients were less likely to have any co-morbidity (29% vs. 52%; P < 0.001), and had higher rates of immunomodulator (IMM) or biologic use. IBD patients with confirmed COVID-19 had lower rates of hospitalizations (14% vs. 51%; P < 0.001) and ICU admissions (2% vs. 13%; P = 0.04; Table 2). On multivariable analysis restricted to confirmed COVID-19, the presence of IBD was not associated with severe outcomes (OR 0.55, 95% CI 0.12-2.44, P = 0.43). Age, male gender, number of comorbidities, thiopurine and steroid use were significant predictors of severe COVID-19 outcomes, while TNF-antagonists had a protective effect (Table 3).
CONCLUSION(S): In this large cohort study, IBD was not a risk factor for severe outcomes of COVID-19. Age, co-morbidities, and exposure to thiopurines and steroids were associated with severe outcomes of COVID-19. TNF-antagonists may be protective from severe outcomes of COVID-19, but this requires further study

BACKGROUND:Ileal pouch-anal anastomosis is a common surgical procedure in patients with an initial diagnosis of ulcerative colitis or indeterminate colitis. Tobacco smoking has been associated with protection from onset of ulcerative colitis. Smoking has been reported to be both a protective factor and a risk factor for the development of pouchitis. AIM/OBJECTIVE:To examine the influence of smoking on the risk of pouchitis. METHODS:We identified 15 studies evaluating smoking as a risk factor for developing pouchitis in ulcerative colitis or indeterminate colitis patients with a history of ileal pouch-anal anastomosis in a systematic search performed from inception through May 4, 2020. A meta-analysis was then performed using a random-effects model to generate risk ratios (RR) and 95% confidence intervals (CI). RESULTS: = 78.5%). CONCLUSIONS:Smoking, past or present, is not associated with an increased risk for the development of pouchitis in patients with ulcerative colitis or indeterminate colitis.