Faculty Bibliography

Background/UNASSIGNED:We quantified loss of response (LOR) to vedolizumab (VDZ) in clinical practice and assessed the effectiveness of VDZ dose intensification for managing LOR. Methods/UNASSIGNED:Retrospective review (May 2014-December 2016) of a prospectively maintained inflammatory bowel disease (IBD) registry. Kaplan-Meier estimates were used to determine rates of LOR to VDZ . Independent predictors of LOR were identified using univariate and multivariable Cox proportional hazard regression. Success of recapturing response (>50% reduction in symptoms from baseline) and remission (complete resolution of symptoms) after dose intensification was quantified. Results/UNASSIGNED:Cumulative rates for VDZ LOR were 20% at 6 months and 35% at 12 months, with slightly lower rates in Crohn's disease than in ulcerative colitis (6 months 15% vs 18% and 12 months 30% vs 39%, P = 0.03). On multivariable analysis, LOR to a tumor necrosis factor (TNF) antagonist before VDZ use was associated with an increased risk for LOR to VDZ [hazard ratio (HR) 1.93; 95% confidence interval (CI) 1.25-2.97] in all patients. For Crohn's disease patients specifically, higher baseline C-reactive protein concentration was associated with increased risk for LOR to VDZ (HR 1.01 per mg/dL increase, 95% CI 1.01-1.02). Shortening of VDZ infusion interval from 8 to every 4 or 6 weeks recaptured response in 49% and remission in 18% of patients. Conclusions/UNASSIGNED:LOR to a TNF antagonist before VDZ use and higher baseline C-reactive protein are important predictors of VDZ LOR. Treatment response can be recaptured in almost half of these patients with VDZ infusion interval shortening.

Background: Nearly one-half of Crohn's disease patients require bowel resection within the frst 10 years of disease (1). Small bowel obstruction (SBO) is the most common indication for surgery in Crohn's patients, followed by abscess and presence of fstulizing disease (2). Tere are little data regarding pharmacologic treatment of Crohn's-associated SBO with corticosteroids. In particular, the safety and efcacy of corticosteroids in treating inflammation in the setting of acute Crohn's SBO remains unclear. METHODS: Our group performed a retrospective chart review of patients admitted with Crohn's-disease associated SBO to our institution. Key variables examined included use of corticosteroids, length of stay, infectious complications, and short-term requirement for surgery. Inclusion criteria included adults (>18 years) who were not pregnant and carried a known diagnosis of Crohn's disease. Using the i2b2 search engine, patients admitted with the ICD10 diagnoses for Crohn's disease and a primary diagnosis of SBO were included. Analysis of outcomes was performed comparing patients who received steroids versus those who did not using t-statistics and chi-square analysis. RESULTS: Between 2015 and 2017, ffy-seven patients met inclusion criteria. Te majority (n=32, 56%) received no corticosteroids for the preceding three months nor during the admission for SBO, while the minority (n=25, 44%) did receive steroids. Te mean age of patients (45+/-19 years vs 46+/-18 years, P=0.92), and duration of Crohn's disease (14+/-13 years vs 14+/-12 years, P=0.93) did not differ between groups. C-reactive peptide (CRP) on admission did not differ between groups (23.9+/-17 vs 46.6+/-78, P=0.49). Eleven patients (19%) required surgery related to Crohn's disease during or within the three months following admission. Tere was no difference in requirement for surgery between groups. In multivariable logistic regression, the only factor associated with requirement for surgery was duration of Crohn's disease (P<0.05). Tere was no difference in duration of nasogastric tube placement, time to PO challenge, or length of hospital stay. Tere were no mortalities in either group and no difference in infectious complications afer discharge. CONCLUSION(S): Tese results suggest that corticosteroids are not associated with improved outcomes in patients with Crohn's associated SBO. Length of stay is not decreased due to use of corticosteroids. Te study is limited by its retrospective design and small sample size. However, future case-control or randomized clinical trials can examine the use of corticosteroids during acute Crohn's-associated SBO

Background: Postoperative ileus (POI) is a temporary delay of coordinated intestinal peristalsis following major abdominal surgery, leading to signifcant symptoms such as nausea, vomiting, abdominal pain, prolonged hospitalization, nosocomial complications, and physical deconditioning. Te use of opioids for postoperative pain control further exacerbates the problem. Opioids bind to the mu receptors in the intestinal tract, leading to gut hypomotility. Alvimopan, an oral, peripherally acting mu-opioid receptor antagonist, was FDA approved in 2008 for use before and afer bowel resection to help prevent and treat POI. Tere are no dedicated studies of alvimopan in patients with inflammatory bowel disease (IBD). Terefore, we conducted a study to investigate alvimopan's role in IBD patients who underwent either laparoscopic or open bowel resection. METHODS: A retrospective chart review was conducted at a 725-bed acute care teaching hospital in New York City between January 2012 and February 2017. Data collected included age, sex, type of IBD, length of stay, post-operative gastrointestinal symptoms (nausea, vomiting, constipation, abdominal distention, frst flatus, frst bowel movement, PO tolerance), and dose of alvimopan, were collected. Te primary outcome was time to GI recovery. Secondary outcomes were: time to frst flatus, time to frst bowel movement, time to tolerating a liquid diet, time to tolerating solid food, and total length of stay. Descriptive statistics reports were created through a secure web-based application called REDCap (Research Electronic Data Capture), and the data were exported into Stata to run further analyses. Of note, approximately 50% of patients who underwent bowel surgery afer March 2015 were placed on a "colon surgery pathwayTM, which is an order set dedicated to strategies that decrease length of stay and post-operative complications. Key features include early feeding, optimized analgesia regimen to allow patients to ambulate, encouraging use of incentive spirometry, and administration of alvimopan peri-procedurally. RESULTS: Of 247 patients, 121 received alvimopan (49.0%) and 126 (51.0%) did not. Te male to female ratio was 51:49. Te mean age of the control group was 44.4 + 16.3 and that of the alvimopan group was 43.2 + 16.4. Patients who received alvimopan had faster GI recovery, with a hazard ratio (HR) of 2.11 (P<0.001), shorter time to frst flatus (HR 2.02, P<0.001), shorter time to frst bowel movement (HR 1.93, P<0.001), shorter time to tolerating liquid diet (HR 2.48, P<0.001), and shorter time to tolerating solid food (HR 2.00, P<0.001). Afer controlling for type of bowel resected (large vs. small bowel), laparoscopic vs. open, age, and type of IBD (ulcerative colitis vs. Crohn's disease) using linear regression, patients who received alvimopan spent 2.59 fewer days in the hospital compared to the control group (P<0.01). CONCLUSION(S): Te results of this study suggest that alvimopan is effective in accelerating the time to GI recovery. Data analysis of all primary and secondary outcomes revealed that alvimopan had a statistically signifcant beneft during the post-operative period of IBD patients undergoing bowel resection. Length of stay for IBD patients was signifcantly decreased with peri-operative use of alvimopan

Introduction: Inflammatory bowel disease (IBD) often requires treatment with immune modulating medications (biologics). Although biologic agents have been shown to have excellent efficacy in treating IBD patients, the substantial cost has become a barrier to treatment for many patients. Recently, biosimilar drugs have been developed. Many clinical trials have demonstrated similar efficacy of biosimilars compared to originator biologics in IBD patients. Patients' perception and knowledge regarding these drugs is not known. We surveyed IBD patients to assess perceptions and knowledge regarding biosimilar medications and willingness to switch from biologics to biosimilars. Methods: 121 consecutive adult patients in a single outpatient gastroenterology clinic with a pre-existing diagnosis of IBD were surveyed between March and May 2017. Data was then compiled and analyzed. Patients were excluded if they were not able to read English. Results: The mean age of the survey participants was 37.8 +/- 15.5 years. Sixty-three percent of the participants were male. Fifty-three patients (43.8%) carried a diagnosis of UC. Sixty-seven patients (55.3%) had Crohn's disease (CD). One patient was not sure of his/her diagnosis. Significantly more CD patients than UC were currently on infliximab or adalimumab (35 vs 16, p=0.014). Only 33 participants (27%) have heard of "biosimilar medications" prior to this study. Seventy-six percent of all participants were uncomfortable using a biosimilar medication that had not been tested in clinical trials specifically for UC or CD. 57% participants were uncomfortable exchanging their current medication for a biosimilar. 92% of all participants wanted to be informed prior to switching to a biosimilar medication. There was a statistically significant correlation between the number of years since diagnosis and the patient's comfort with switching to a biosimilar medication (r=0.203, p=0.027). Conclusion: By investigating patient perceptions and knowledge regarding biosimilars, we hope to better understand patients' level of comfort, preferences, and potential barriers to implementation. Most IBD patients were uncomfortable using a biosimilar that has not been evaluate in a clinical trial in IBD. Of interest, a longer time since diagnosis of CD was associated with increased comfort of switching from biologic to biosimilar. This information will help physicians form their approach to introducing and discussing these biosimilars with patients. (Table Presented)

Introduction: Clostridium difficile infection (CDI) occurs frequently in patients with inflammatory bowel disease (IBD) and is associated with increased disease activity. Due to concern for complications, immunosuppressive medication (ISM) is often withheld after CDI, although few data exist to inform this decision. This study aims to assess the influence of ISM on outcomes following CDI in IBD patients. Methods: This multicenter, retrospective cohort study was performed at 4 academic medical centers in New York City. Patient demographic and clinical data was abstracted from databases at each site for adult patients with an established diagnosis of IBD also diagnosed with CDI. Escalation of therapy was defined as initiation or dose escalation of corticosteroids or new biologic use following antibiotic therapy for CDI. Outcomes were assessed at 30 and 90 days after last positive C. difficile test. Continuous variables were compared using two-sided T-tests and proportions were compared using Chi-squared tests. Exact methods were used for expected cell size. Results: 207 patients met inclusion criteria (49 outpatient, 158 inpatient). Demographic information is listed in Table 1. Escalation of IBD regimen (Table 2) was more frequent in outpatients at 90 days (43% vs. 22%, P<0.01), with 49% (39/61) of ISM escalation occurring within 14 days of CDI.) Patients not escalated had higher rates of sepsis than escalated patients (11% vs. 2%, P=0.04). Severe outcomes (death, sepsis, or colectomy) at 90 days were markedly increased in the non-escalation group (15% vs 2%, P<0.01). There was no difference in CDI recurrence or rehospitalization between groups. Conclusion: In this multicenter study assessing outcomes of ISM use in patients with IBD and CDI, initiation of steroid or biologic therapy following CDI treatment was not associated with adverse clinical outcomes. While no difference was observed between CDI recurrence or rehospitalization among groups, sepsis and severe outcomes were significantly more common in patients not undergoing escalation. These data suggest that escalation of IBD therapy following CDI is not associated with worse clinical outcomes and a subset of patients may benefit from timely treatment of underlying inflammatory disease. Prospective studies are needed to validate these data and to inform clinical guidelines regarding the timing of ISM use following CDI

Introduction: Colonoscopy is the most commonly used test for colorectal cancer screening in the US, but patients often find the oral bowel preparation difficult, inconvenient, or intolerable. Suboptimal bowel prep occurs in 20-24% of colonoscopies, leading to inadequate examinations that necessitate additional procedures. Colonic irrigation is an FDA-approved method of colon cleansing using a warm water lavage, but few studies have evaluated it as preparation for colonoscopy. The purpose of this study is to evaluate colonic irrigation as an alternative to oral bowel prep in patients undergoing screening/ surveillance colonoscopy. Methods: We conducted a single-center, single-arm feasibility study using the Hydro-San Plus system. Patients followed a low-residue diet and took 2 doses of polyethylene glycol the day before the procedure. Colonoscopy was performed immediately following colonic irrigation. Boston Bowel Prep Scale (BBPS) and adverse events were recorded. A telephone questionnaire was administered within 7 days of the procedure. Results: Of the 21 patients enrolled, 48% had at a medical risk factor for poor prep (Table 1). Eighteen patients completed irrigation, of whom 12 (67%) had an adequate bowel prep, defined as BBPS>1 in all segments (Table 2). Two irrigations were not completed due to minor adverse events (discomfort from speculum insertion and rectal abrasion) and 1 was aborted for mechanical repair. There were no major adverse events. Patients with no risk factors for poor prep were 4 times more likely to have an adequate prep, although this was not statistically significant (P=0.14). Half of the patients felt that irrigation was easy (47%) and comfortable (53%), while most felt it was tolerable (71%) and convenient (82%). Among participants who had previous a colonoscopy with oral prep, the majority felt that irrigation was easier (85%), more tolerable (77%), and more convenient (85%) than oral prep. 82% of respondents said they would ask for irrigation again and only 12% said they would refuse if it were offered. Conclusion: Colonic irrigation is a safe and moderately efficacious alternative to oral bowel prep for screening/surveillance colonoscopy. A more potent oral pre-prep, especially for patients with risk factors for poor prep, may improve efficacy. Importantly, patient satisfaction with colonic irrigation appears to be higher than with oral bowel prep. (Table Presented)

Introduction: Inflammatory bowel disease (IBD) therapy is continuously evolving with novel drugs targeting various inflammatory pathways. Ustekinumab (USK), a monoclonal antibody inhibiting the IL-12/23 pathway, was approved in September 2016 to treat moderate-to-severe Crohn's disease (CD). While safety data in IBD is limited, USK has been used to treat other autoimmune diseases with favorable safety profiles. We aimed to establish rates of adverse events (AE) and demonstrate non-inferiority of AE of USK compared to placebo and other biologics. Methods: MEDLINE, PubMed and Embase databases were searched in May 2017 using terms "ustekinumab" and "clinical trials." Two authors independently performed quality assessment and dual extraction. Randomized control trials comparing USK to placebo or other biologics regardless of disease were included. The primary outcome was the odds ratio (OR) of AE of USK vs placebo, expressed as pooled OR and 95% confidence interval (CI). Secondary outcomes included OR of mild/moderate and serious AE (SAE) in USK vs placebo, USK vs biologics, and low vs high-dose USK, respectively (Table 2). A sub-analysis of outcomes in CD trials was performed. Random effects meta-analysis was performed for all outcomes. Results: 16 papers with 6756 subjects (44% female) were included (Fig 1). Infections were the most common AE (Table 1). The OR of serious AE in USK vs placebo was 0.76 (95% CI 0.56-1.03, Fig 2). The OR of mild-to-moderate AE in the USK vs placebo was 1.12 (95% CI 1.01-1.24), suggesting increased risk of mild/moderate AE with USK (Fig 3). However, this was no longer significant after sub-analysis of the three CD trials. Analysis of 5 trials comparing low vs high-dose USK revealed an OR of 0.96 (95% CI 0.46-2.04) for SAE and 1.17 (95% CI 0.98-1.39) for mild-to-moderate AE. Use of USK was not associated with increased AE compared to other biologics, with OR of 0.91 (95% CI 0.61-1.35) for SAE and 0.98 (95% CI 0.85-1.13) for mild/moderate AE. Heterogeneity was low for all calculations. Conclusion: USK has a comparable safety profile to placebo and other biologics in the treatment of various diseases, although we did find a mildly elevated risk of mild/moderate AE with USK; however, this (Figure Presented) was not seen in CD trials. The favorable safety profile of USK is of clinical importance with the advent of USK in CD and ongoing clinical trials for ulcerative colitis. More data on long-term safety data in the IBD population is needed

BACKGROUND: Inflammatory bowel diseases (IBD) are believed to be driven by dysregulated interactions between the host and the gut microbiota. Our goal is to characterize and infer relationships between mucosal T cells, the host tissue environment, and microbial communities in patients with IBD who will serve as basis for mechanistic studies on human IBD. METHODS: We characterized mucosal CD4 T cells using flow cytometry, along with matching mucosal global gene expression and microbial communities data from 35 pinch biopsy samples from patients with IBD. We analyzed these data sets using an integrated framework to identify predictors of inflammatory states and then reproduced some of the putative relationships formed among these predictors by analyzing data from the pediatric RISK cohort. RESULTS: We identified 26 predictors from our combined data set that were effective in distinguishing between regions of the intestine undergoing active inflammation and regions that were normal. Network analysis on these 26 predictors revealed SAA1 as the most connected node linking the abundance of the genus Bacteroides with the production of IL17 and IL22 by CD4 T cells. These SAA1-linked microbial and transcriptome interactions were further reproduced with data from the pediatric IBD RISK cohort. CONCLUSIONS: This study identifies expression of SAA1 as an important link between mucosal T cells, microbial communities, and their tissue environment in patients with IBD. A combination of T cell effector function data, gene expression and microbial profiling can distinguish between intestinal inflammatory states in IBD regardless of disease types.