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 incidence and prevalence of inflammatory bowel disease (IBD) is rising in the elderly population. Compared with patients with onset during their younger years, patients with elderly onset IBD have a distinct clinical presentation, disease phenotype, and natural history. Genetics contribute less to pathogenesis of disease, whereas biological changes associated with aging including immunosenescence, dysbiosis, and frailty have a greater impact on disease outcomes. With the advent of an increasingly wider array of biologic and small-molecule therapeutic options, data regarding efficacy and safety of these agents in elderly IBD patients specifically are paramount, given the unique characteristics of this population.

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.

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: Gastrointestinal symptoms of SARS-CoV-2 infection common, but usually mild in severity. We describe a case of severe gastrointestinal bleeding (GIB) in a patient with a COVID-19 associated hyperinflammatory response. CASE DESCRIPTION/METHODS: A 25-year-old man with no significant medical history presented with 2 weeks of fevers, cough, dyspnea, and diarrhea. He tested positive for COVID-19 on nasopharyngeal PCR and imaging showed multifocal pneumonia. Initial labs were notable for markedly elevated CRP and ferritin, pancytopenia and acute kidney injury. He was treated for suspected COVID-19 associated hyperinflammatory syndrome with anakinra (5 mg/kg twice daily) and hydroxychloroquine. He became anuric requiring hemodialysis and renal biopsy complicated by retroperitoneal bleeding and emergent embolization of the left renal artery. He was intubated for worsening acute respiratory distress syndrome (ARDS) and developed hematemesis and melena leading to hemorrhagic shock. EGD showed diffuse inflammation, erosions and oozing from the esophagus to the proximal duodenum, non-bleeding gastric ulcers and petechiae (Figure 1A, B). Given clinical suspicion for COVID-19 associated macrophage activation syndrome (MAS)/ secondary hemophagocytic lymphohistiocytosis (sHLH), anakinra was restarted and intravenous immunoglobulin (IVIG, 1mg/kg) was given with clinical improvement. The patient continued to have melena. Repeat EGD showed severe esophagitis with large clots and sloughing mucosa, a focal 3-4 cm area of necrosis in the fundus, unresolved non-bleeding stomach ulcers and improved duodenitis from prior (Figure 1C, D). DISCUSSION: We describe a case of a young adult who developed catastrophic GIB as a complication of COVID-19. The pathogenesis of SARS-CoV2 infection is incompletely understood, but there is mounting evidence that it can induce a MAS/sHLH-like hyperinflammatory response. Several laboratory hallmarks of COVID-19 infection are also seen in MAS/sHLH including elevated CRP, ferritin, IL-1, and IL-6. This hyperinflammatory response can manifest in a variety of ways, including a Kawasaki-like presentation in pediatric patients responsive to IVIG and IL-1 antagonism. GIB is rare in COVID-19, occurring in 4% of cases, but can occur in up to 20% of MAS/sHLH cases. Clinicians should recognize that COVID-19 can provoke a MAS/sHLH-like hyperinflammatory syndrome with gastrointestinal involvement

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

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.

BACKGROUND AND AIM/OBJECTIVE:Rifaximin is an antimicrobial which is used for prophylaxis of hepatic encephalopathy in patients with cirrhosis and has known anti-Clostridioides difficile activity. The aim of this study is to assess whether the rate of C. difficile infection (CDI) is decreased in patients with cirrhosis on chronic rifaximin compared with those who are not. METHODS:We retrospectively identified consecutive patients admitted to Montefiore Medical Center from 2010 to 2014 with cirrhosis and diarrhea who were tested for CDI. Demographics, comorbidities, medication exposure, baseline laboratory data, and outcomes were recorded. Patients with cirrhosis and diarrhea on chronic rifaximin were compared with those not on rifaximin. The chronic rifaximin group was then isolated, and those with and without CDI were compared. RESULTS:Of 701 patients with cirrhosis and diarrhea, 149 were on chronic rifaximin and 552 were not. 12.8% of patients on chronic rifaximin had CDI compared with 29.7% of those not on rifaximin (P < 0.001). Patients on rifaximin had higher MELD (19.7 vs. 15.5, P < 0.001), 30-day mortality (26.2% vs. 16.1%, P < 0.01), and ICU requirement compared with those not on rifaximin. CONCLUSION/CONCLUSIONS:Patients with cirrhosis who are on chronic rifaximin have decreased rates of CDI compared with those not on this therapy. Despite its risk for promoting resistance, chronic rifaximin use may have a beneficial effect in preventing CDI in patients with cirrhosis.

BACKGROUND:Clostridium difficile infection (CDI) is the most common nosocomial infection in the US and cirrhotic patients with CDI have increased risk for poor outcome. AIM:The aim of this study is to evaluate the impact of CDI on short-term mortality in patients with cirrhosis and identify predictors of mortality in these patients. METHODS:We retrospectively identified patients at Montefiore Medical Center from 2010 to 2014 with cirrhosis, diarrhea and a C. difficile toxin assay. Demographics, co-morbidities, medications, laboratory data and outcomes were recorded. RESULTS:Of 701 patients with cirrhosis who had a CDI assay, 183 were CDI+ and 518 CDI-. Patients with CDI were older, had more frequent CKD on hemodialysis and heart failure, were less frequently on rifaximin and lactulose and had increased glucocorticoid exposure. 30-day mortality was higher in patients with CDI (23.0% vs 16.6%, p < 0.05) compared to those without. Univariate predictors of 30-day mortality included WBC, corticosteroid use, AST, ALT, MELD, albumin, HBV and HCV infection; however, via multivariate analysis, only MELD (HR: 1.04 ± 0.02, p < 0.05) remained significant. CONCLUSION:Patients with cirrhosis and CDI are at greater risk of 30-day mortality than those without CDI and the only multivariate predictor of mortality is MELD. These patients should have their disease severity triaged based upon MELD score.