Faculty Bibliography

BACKGROUND & AIMS:There are few real-world data on the safety of vedolizumab for treatment of Crohn's disease (CD) or ulcerative colitis (UC). We quantified rates and identified factors significantly associated with infectious and non-infectious adverse events in clinical practice. METHODS:We performed a retrospective review of data from a multicenter consortium database (from May 2014 through June 2017). Infectious and non-infectious adverse events were defined as those requiring antibiotics, hospitalization, vedolizumab discontinuation, or resulting in death. Rates were quantified as proportions and events per 100 patient years of exposure (PYE) or follow up (PYF). We performed multivariable logistic regression analyses to identify factors significantly associated with events and reported as odds ratios (OR) with 95% CIs. RESULTS:Our analysis comprised 1087 patients (650 with CD and 437 with UC; 55% female; median age, 37 years) with 861 PYE and 955 PYF. Infections were observed in 68 patients (6.3%; 7.9 per 100 PYE, 7.1 per 100 PYF); gastrointestinal infections (n = 31, 2.4 per 100 PYE, 2.2 per 100 PYF) and respiratory infections (n = 14, 1.6 per 100 PYE, 1.5 per 100 PYF) were the most common. Arthralgias were the most common non-infectious adverse events (n = 31, 2.9%; 3.6 per 100 PYE). Two patients developed malignancies (squamous cell skin cancer and colorectal cancer; 0.23 per 100 PYE, 0.21 per 100 PYF). Active smoker status (OR, 3.39) and number of concomitant immunosuppressive agents (corticosteroids or immunomodulators; OR, 1.72 per agent) used were independently associated with infections. CONCLUSION:In a retrospective cohort study of patients with IBD, we found vedolizumab to be well tolerated with an overall favorable safety profile. Active smoking and concomitant use of immunosuppressive agents were independently associated with infections.

Background/UNASSIGNED:Clostridium difficile infection (CDI) is common in patients with inflammatory bowel disease (IBD), often leading to diagnostic confusion and delays in IBD therapy escalation. This study sought to assess outcomes after CDI in IBD patients exposed to new or escalated immunosuppressive therapy. Methods/UNASSIGNED:This multicenter retrospective cohort study included IBD patients with documented CDI at 4 academic medical centers. Data were abstracted from clinical databases at each institution. Outcomes at 30 and 90 days were compared between patients undergoing new or intensified immunosuppressive therapy and those without therapy escalation. Continuous variables were compared using t tests, and proportions using chi-square tests. Multivariable logistic regression was used to determine the association of individual variables with severe outcomes (including death, sepsis, and/or colectomy) within 90 days. Secondary outcomes included CDI recurrence, rehospitalization, worsening of IBD, and severe outcomes within 30 days. Results/UNASSIGNED:A total of 207 adult patients with IBD and CDI were included, of whom 62 underwent escalation to biologic or corticosteroid therapy (median time to escalation, 13 days). Severe outcomes within 90 days occurred in 21 (15.6%) nonescalated and 1 (1.8%) therapy-escalated patients. Serum albumin <2.5 mg/dL, lactate >2.2 mg/dL, intensive care unit admission, hypotension, and comorbid disease were associated with severe outcomes. Likelihood of severe outcomes was decreased in patients undergoing escalation of IBD therapy after CDI (adjusted odds ratio [aOR], 0.12) and increased among patients aged >65 years (aOR, 4.55). Conclusions/UNASSIGNED:Therapy escalation for IBD within 90 days of CDI was not associated with worse clinical outcomes. Initiation of immunosuppression for active IBD may therefore be appropriate in carefully selected patients after treatment of CDI.

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:Vedolizumab is now widely available for the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD). We sought to quantify the rates of postoperative complications with preoperative vedolizumab compared with anti-tumor necrosis factor (anti-TNF) therapy. Methods:A multicenter retrospective review of adult inflammatory bowel disease (IBD) patients who underwent an abdominal operation between May 20, 2014, and December 31, 2015, was performed. The study cohort was comprised of patients who had received vedolizumab within 12 weeks of their abdominal operation, and the control cohort was IBD patients who had received anti-TNF therapy. Results:A total of 146 patients received vedolizumab within 12 weeks before an abdominal operation (64% female; n = 93; median age, 33 years; range, 15-74 years), and 289 patients received anti-TNF therapy (49% female; n = 142; median age, 36 years; range, 17-73 years). Vedolizumab-treated patients were younger (P = 0.015) and were more likely to have taken corticosteroids (P < 0.01) within the 12 weeks before surgery. Vedolizumab-treated patients had a significantly increased risk of any postoperative surgical site infection (SSI; P < 0.01), superficial SSI (P < 0.01), deep space SSI (P = 0.39), and mucocutaneous separation of the diverting stoma (P < 0.00) as compared with patients taking anti-TNF therapy. On multivariate analysis, after adjusting for body mass index, steroids at the time of operation, and institution, exposure to vedolizumab remained a significant predictor of postoperative SSI (P < 0.01). Conclusions:We observed that vedolizumab-treated patients were at significantly increased risk of postoperative SSIs after a major abdominal operation, as compared with anti-TNF-treated patients.

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)