Faculty Bibliography

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

INTRODUCTION: 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 the effectiveness and safety in the real world are limited. We describe the effectiveness and safety of ustekinumab in patients with UC from two US tertiary IBD centers.
METHOD(S): Patients with moderately to severely active UC treated with ustekinumab at NYU Langone Medical Center (New York, NY) and University of Chicago Medical Center (Chicago, IL) 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.
RESULT(S): Sixty-six UC patients were included (Table 1). 61% of patients had extensive colitis and overall mean total Mayo score was 6.5 +/- 2.4. 92% of patients had prior exposure to biologics or tofacitinib. 43% and 45% of patients achieved clinical remission by 3 and 12 months, respectively (Figure 1). Anti-TNF non-response and endoscopic Mayo score of 3 were negative predictors of clinical remission at 3 months (Table 2). At 1 year, 50% of patients achieved endoscopic remission and 33% achieved mucosal and histo-endoscopic healing. The achievement of histo-endoscopic healing was significantly associated with lower partial Mayo score (0.5 +/- 0.6 vs. 3.5 +/- 1.7; P < 0.01) and lower stool frequency (0.3 +/- 0.5 vs. 1.4 +/- 0.7; P = 0.02). Serious adverse events occurred in 4 (6%) patients (3 UC exacerbations, 1 vasculitis).
CONCLUSION(S): In this cohort of mostly biologic-refractory UC patients, treatment with usteki-numab 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

INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) is a common surgical procedure in patients with an initial diagnosis of ulcerative colitis (UC), indeterminate colitis (IC), or familial adenomatous polyposis syndrome (FAP). Tobacco smoking has been associated with protection from onset of UC. Smoking has been reported to be both a protective factor and a risk factor for the development of pouchitis. In this systematic review and meta-analysis, we examine the influence of smoking on the risk of pouchitis.
METHOD(S): We identified 16 studies evaluating smoking as a risk factor for developing pouchitis in patients with a history of IPAA in a systematic search performed from inception through May 2020. A meta-analysis was then performed using a random-effects model to generate risk ratios.
RESULT(S): A total of 2,389 IPAA patients were included in the systematic review and meta-analysis. In the included studies, the percentage of patients with a diagnosis of pouchitis ranged from 22% to 72%. The percentage of patients with a history of smoking ranged from 7% to 63%. In total, 919 patients had pouchitis (330 current or former smokers; 589 non-smokers), and 1,470 patients did not have pouchitis (485 current or former smokers; 985 non-smokers). A history of smoking compared with never smoking was not associated with an increased risk of developing pouchitis (RR = 0.96, 95% CI 0.78-1.17, I² 5 68.6%). There was also no significant risk of pouchitis when comparing current smokers versus non-smokers (RR = 1.09, 95% CI 0.93-1.28, I² 5 0%) and former smokers versus non-smokers (RR = 0.95, 95% CI 0.70-1.28, I² 5 79.8%).
CONCLUSION(S): Smoking, past or present, is not associated with an increased risk for the development of pouchitis. This is important to consider when counseling patients on the risks of smoking and pouchitis

INTRODUCTION: Guidelines recommend testing inflammatory bowel disease (IBD) patients hospitalized with flare for Clostridioides difficile infection (CDI), though little is known about whether a delay in testing for CDI is related to adverse outcomes. We examined the relationship between time to C. difficile PCR test order, collection, and result with adverse IBD outcomes.
METHOD(S): We performed a retrospective cohort study of IBD patients hospitalized with flare through the emergency department (ED) between 2013 and January 2020 at an urban academic medical center. The time from ED presentation to CDI test order (time-to-order), sample collection (time-to-collection), and test result (time-to-result) were collected. Time-to-result was stratified by within+/-hours, 6-24 hours, and 24 hours or longer. The primary outcome was length of stay (LOS). Secondary outcomes were inpatient anti-TNF administration and surgery. Separately, we used initial hemodynamic and laboratory values to create an IBD hospitalization severity score for evaluation against LOS and time-dependent variables.
RESULT(S): We identified 122 IBD patients hospitalized with flare. There were no significant differences in baseline characteristics among time-to-result groups. There was no difference in time-toorder between the+/-hours and 6-24 hours groups (Table 1). Despite a shorter time-to-result, the average LOS in the+/-hours group was 7.3 days, longer compared to the 6-24 hours group (4.3 days, P=0.018) and the 24 hours group (4.2 days, P=0.035Table 1). There were no differences in inpatient anti-TNF administration (P=0.10) or surgery (P=0.08) among time-to-result groups. Markers of disease severity correlated with longer LOS and earlier time-to-result (Table 2). A composite of these markers was used to stratify patients by disease severity. Those with more severe disease had earlier times-to-result (12.8 hours vs. 32.2 hours, P=0.014) and had a longer LOS (7.9 vs. 3.4 days, P=0.007) with no difference in time-to-order compared to patients with less severe disease (P=0.09Table 3).
CONCLUSION(S): Earlier time-to-result for CDI is associated with longer LOS in IBD patients hospitalized with flare. This inverse relationship is confounded by disease severity at presentation. Patients with more severe disease have a shorter time-to-result and a longer LOS without any difference in time-to-order. Delay in testing was not associated with higher rates of inpatient anti- TNF administration or surgery

INTRODUCTION: Inflammatory bowel disease (IBD) can have a detrimental effect on patients' functional capacity. Recently, a self-report version of the IBD Disability Index (IBD-DI) was developed to assess how disease burden affects patients' ability to work and maintain relationships. There have been few studies tracking IBD-DI over time or with treatment of disease.
METHOD(S): We prospectively identified patients with Crohn's disease (CD) and ulcerative colitis (UC) starting a new biologic agent (anti-TNF, anti-integrin, or anti IL12/23). Patients were surveyed at induction of therapy and 60 days after, approximating the start of maintenance. Surveys included clinical disease activity indices [Harvey Bradshaw Index (HBI), Simple Clinical Colitis Activity Index (SCCAI), partial Mayo Score] and scales that assessed depression (PHQ-9), quality of life [Short IBD Questionnaire (SIBDQ)]), illness perception [Brief Illness Perception Questionnaire (BIPQ)], and IBD-DI (with higher sores indicating more disability). We reviewed baseline colonoscopies (simple endoscopic and Mayo endoscopic subscore), biomarkers of inflammation (ESR, CRP, calprotectin), comorbidities, and IBD history.
RESULT(S): 61 patients (35 males and 26 females) completed the induction survey and 35 completed survey 2. The mean age was 34 years, 59% had CD, 41% had UC, and 38% were non-white (Table 1). There was a strong correlation between the IBD-DI and the HBI, SIBDQ, and PHQ-9 (r = 0.62, 0.81, 0.82, P < 0.001; Table 2). There was a moderate correlation with SCCAI (r = 0.53, P < 0.01), Mayo and pMayo (r = 0.44, r = 0.39, P < 0.001), and with the domains of the BIPQ assessing illness effect on wellbeing, symptoms and emotions (P < 0.001). The IBD-DI did not correlate with baseline biomarkers of inflammation or endoscopic scores. There were no statistically significant differences in IBD-DI scores between males and females or between patients with CD or UC (Table 3). There was a statistically significant improvement in IBD-DI scores from survey 1 to survey 2 (mean 33.9 out of 100 to 27.1, P < 0.001).
CONCLUSION(S): In this prospective cohort, there was a strong correlation between IBD-DI and indices of disease activity, depression, and quality of life. There was an improvement in IBD-DI scores after induction with biologics. This is the first study to assess this metric longitudinally and with treatment of disease using the self-report IBD-DI. Future studies must track the IBD-DI during maintenance therapy and assess how it relates to therapeutic response

INTRODUCTION: Utilizing recently-developed inflammatory bowel disease (IBD)-specific scales, we aimed to correlate sexual dysfunction (SD) with clinical and psychosocial IBD metrics, and track SD longitudinally, specifically in patients initiating biologic therapies.
METHOD(S): We surveyed Crohn's disease (CD) and ulcerative colitis (UC) patients starting a biologic agent (anti-TNF, anti-integrin, or anti-IL12/23) at induction of therapy and 60 days after. Surveys included the IBD- Female and Male Sexual Dysfunction Scales (IBD-FSDS and MSDS), the PROMIS Brief Sexual Function and Satisfaction Profile, as well as disease activity indices [Harvey-Bradshaw index (HBI), partial Mayo score], and scales for depression [Patient Health Questionnaire-9 (PHQ-9)], quality of life (QoL) [Short IBD Questionnaire (SIBDQ)], functional disability [IBD-Disability Index (IBDDI)], and illness perception [Brief Illness Perception Questionnaire (BIPQ)]. We reviewed baseline colonoscopies [simple endoscopic score (SES) and Mayo endoscopic subscore (MES)], biomarkers of inflammation (ESR, CRP, calprotectin), comorbidities, and IBD history.
RESULT(S): 61 patients (35 males and 26 females) completed survey 1 and 35 completed survey 2. The mean age was 34 years, 59% had CD, 41% had UC, and 38% were non-white. At induction, there was a high degree of SD as measured by the MSDS and FSDS (mean MSDS 9, FSDS 15). Initial SD scores were strongly correlated with PROMIS scores (r = 0.82, P < 0.001) and MES (r = 0.74, P < 0.001), and moderately correlated with the HBI (r = 0.48, P = 0.003) and Mayo score (0.46, P = 0.03). SD also correlated with the SIBDQ (r = 0.54, P < 0.001), PHQ-9 (r = 0.41, P < 0.001), IBDDI (r = 0.46, P < 0.001), and with domains of the BIPQ assessing illness effect on emotions and wellbeing (r = 0.58, P < 0.001; r = 0.50, P < 0.001). SD did not correlate with baseline biomarkers of inflammation (Table 2). FSDS scores improved from survey 1 to 2 (mean 18.2 to 11.3, P = 0.01). MSDS scores also numerically improved (10.1 to 8.5), but did not reach significance (Table 3). HBI, SCCAI and pMayo scores improved with a clinically significant response seen in 22% of patients.
CONCLUSION(S): In this prospective observational cohort, SD scores correlated with depression, QoL metrics, and disease activity, but did not correlate with biomarkers of inflammation. There was a moderate improvement in disease activity and SD scores after induction therapy with biologics, but a degree of SD persisted. Further studies must track this effect during maintenance therapy

Background/UNASSIGNED:The Swedish Quality Register for Inflammatory Bowel Disease (SWIBREG) contains clinical data for the study of inflammatory bowel disease (IBD). The Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort was recently established for the study of gastrointestinal histopathology. We aimed to develop and validate a histology score from ESPRESSO using clinical information from SWIBREG, and secondarily, to evaluate the association of the score on IBD-related hospitalization. Methods/UNASSIGNED:In a nationwide, population-based cohort study of patients with IBD during 1969-2017, we linked endoscopic inflammation in SWIBREG with histologic inflammation in ESPRESSO. We established a clinically interpretable model for predicting the endoscopic score from histology using scalable Bayesian rule lists to define a SNOMED-based histology score applicable to the ESPRESSO cohort. We also assessed the impact of baseline endoscopic and histology scores on time to IBD-related hospitalization. Results/UNASSIGNED:We identified 5225 individuals with IBD comprising 11,051 endoscopic assessments in SWIBREG linked to a histopathology record in ESPRESSO. We created predictive models to calculate a SNOMED-based histology score which predicted the endoscopic score. Split-sample validated areas under the ROC curves for the score predicting a non-zero endoscopic score were 0.80 (0.78-0.81) in UC, 0.70 (0.68-0.72) in CD, and 0.76 (0.73-0.78) in IBD-U. In a subset of 2741 individuals with an initial IBD diagnosis and a corresponding record in ESPRESSO with an endoscopic assessment in SWIBREG, the baseline endoscopic and histology scores were associated with time to IBD-related hospitalization (endoscopy log-rank UC p<0.001, CD p=0.020, IBD-U p<0.001; histology log-rank UC p=0.018, CD p=0.960, IBD-U p=0.034). Conclusion/UNASSIGNED:Histopathology data in ESPRESSO accurately predict endoscopic scores in SWIBREG. Baseline endoscopic and histologic scores were associated with time to IBD-related hospitalization, particularly in UC. The SNOMED-based histology score can be used as a measure of disease activity in future register-based IBD studies.

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.

Patients with inflammatory bowel disease (IBD) are at an increased risk of developing intestinal neoplasia-particularly colorectal neoplasia, including dysplasia and colorectal cancer (CRC)-as a primary consequence of chronic inflammation. While the current incidence of CRC in IBD is lower compared with prior decades, due, in large part, to more effective therapies and improved colonoscopic technologies, CRC still accounts for a significant proportion of IBD-related deaths. The focus of this review is on the pathogenesis; epidemiology, including disease- and patient-related risk factors; diagnosis; surveillance; and management of IBD-associated neoplasia.