Faculty Bibliography

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

First detected in Wuhan, China, the novel 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA beta-coronavirus responsible for an unprecedented, worldwide pandemic caused by COVID-19. Optimal management of immunosuppression in inflammatory bowel disease (IBD) patients with COVID-19 infection currently is based on expert opinion, given the novelty of the infection and the corresponding lack of high-level evidence in patients with immune-mediated conditions. There are limited data regarding IBD patients with COVID-19 and no data regarding early pregnancy in the era of COVID-19. This article describes a patient with acute severe ulcerative colitis (UC) during her first trimester of pregnancy who also has COVID-19. The case presentation is followed by a review of the literature to date on COVID-19 in regard to inflammatory bowel disease and pregnancy, respectively.

BACKGROUND AND AIMS/OBJECTIVE:Little is known about the clinical significance of indefinite dysplasia (IND) in patients with inflammatory bowel diseases (IBD) undergoing colonoscopic surveillance for colorectal neoplasia. METHODS:We conducted a retrospective cohort analysis of 492 patients with colonic IBD for 8 or more years or concomitant primary sclerosing cholangitis, with no history of advanced colorectal neoplasia (high-grade dysplasia or colorectal cancer) or colectomy, undergoing colorectal neoplasia surveillance at tertiary IBD referral center from 2001 through 2017. Subjects received consistent histopathologic grading of dysplasia. We collected data on time to development of (advanced) colorectal neoplasia or colectomy using Kaplan Meier methods. We identified factors independently associated with (advanced) colorectal neoplasia with multivariable Cox regression analysis. RESULTS:After 2149 person-years of follow-up, 53 patients (10.8%) received a diagnosis of IND without prior or synchronous low-grade dysplasia (LGD). Compared to patients without dysplasia, patients with IND had a significantly higher risk of advanced colorectal neoplasia (adjusted hazard ratio, 6.85; 95% CI, 1.78-26.4) and colorectal neoplasia (adjusted hazard ratio, 3.25; 95% CI, 1.50-7.05), but not colectomy (P=.78). Compared to IND, LGD was associated with a significantly higher risk of advanced colorectal neoplasia (P=.05). Following a diagnosis of no dysplasia, IND only, or LGD, the incidence rates of advanced colorectal neoplasia were 0.4% per patient-year, 3.1% per patient-year, and 8.4% per patient-year, respectively. CONCLUSIONS:In a retrospective analysis of patients with IBD undergoing colorectal neoplasia surveillance with consistent histopathologic grading of dysplasia, IND was independently associated with a significant increase in risk of advanced colorectal neoplasia. These findings require validation and if confirmed, a reappraisal of the colorectal neoplasia surveillance guidelines.

BACKGROUND:The initiating events of chronic gastrointestinal (GI) inflammation in Crohn's disease (CD) and ulcerative colitis (UC) are not well-defined, but GI infections are implicated. AIMS/OBJECTIVE:To define the role of GI infections in risk of incident inflammatory bowel disease (IBD) and synthesise the current body of relevant translational data to provide biological context for associations between GI infections and IBD risk. METHODS:We systematically reviewed electronic databases through February 2020. Clinical studies that provided risk estimates of the association between GI infections and incident IBD were included. Inclusion criteria were broader for translational studies aiming to define mechanisms of GI infections and predisposition to or protection from IBD. RESULTS:Of the studies identified, 63 met full inclusion criteria. Among studies of clinical gastroenteritis, bacteria-specifically, Salmonella species, Campylobacter species and Clostridioides difficile-demonstrated consistent positive associations with risk of incident IBD. Of viruses, norovirus was associated with increased risk of incident CD. Regarding inverse associations with incident IBD, Helicobacter pylori and helminth infections were associated with a generally consistent reduced risk of IBD. Based on a qualitative analysis of the translational data, putative mechanisms involve multiple microbial and immunologic pathways. CONCLUSIONS:Based on this systematic review, certain enteric pathogens are associated with an increased risk of incident IBD, while others are potentially protective. Prospective studies are required to clarify the clinical implications of these enteric pathogens on the risk and course of IBD, not to mention possible therapeutic or preventative benefit.

BACKGROUND & AIMS/OBJECTIVE:Exposure to hormone contraception has been associated with an increased risk of relapse of inflammatory bowel diseases (IBD). Little is known about the effects of cancer therapies, specifically hormone therapies, on the course of IBD. METHODS:We conducted a retrospective cohort study, collecting data from 5 medical centers on patients with IBD who received a subsequent diagnosis of breast or prostate cancer from 1997 through 2018. For patients with quiescent IBD at their cancer diagnosis, the primary outcome was relapse of IBD. For patients with active IBD at their cancer diagnosis, the primary outcome was IBD remission. RESULTS:Our analysis included 447 patients with IBD (44% with Crohn's disease, 53% with ulcerative colitis, and 3% with IBD-unclassified) who had either breast (78%) or prostate (22%) cancer. At their cancer diagnosis, 400 patients (90%) had inactive IBD, and 47 (10%) had active IBD. Among patients with inactive IBD, 112 (28%) developed active IBD. Previous exposure to steroids, immunomodulators, or biologics was associated with IBD relapse following a cancer diagnosis (hazard ratio [HR] for steroids, 1.79; 95% CI, 1.18-2.71; HR for immunomodulators, 2.22; 95% CI, 1.38-3.55; HR for biologics, 1.95; 95% CI, 1.01-5.36). Hormone monotherapy (HR, 2.00; 95% CI, 1.21-3.29) and combination cytotoxic and hormone therapy (HR, 1.86; 95% CI, 1.01-3.43) was associated with IBD relapse. Among 34 patients who received only cytotoxic chemotherapy, 75% remained in remission from IBD at 250 months compared with 42% of those who received hormone monotherapy (log rank=0.02). Among patients with active IBD at their cancer diagnosis, 14 (30%) entered remission from IBD, but there were no significant factors of achieving IBD remission. CONCLUSIONS:In a multicenter retrospective study, we found that patients with IBD and breast or prostate cancer who receive hormone therapy have an increased risk for relapse of IBD and related adverse outcomes.