Faculty Bibliography

BACKGROUND:Case series suggest a possible association between bariatric surgery and incident IBD. AIM/OBJECTIVE:The aim of this study was to evaluate the association between bariatric surgery and new-onset IBD. METHODS:We first conducted a multi-institutional case series of patients with a history of IBD and bariatric surgery. We next conducted a matched case-control study using medical and pharmacy claims from 2008 to 2012 in a US national database from Source Healthcare Analytics LLC. Bariatric surgery was defined by ICD-9 or CPT code. Bariatric surgery was evaluated as recent (code in database timeframe), past (past history V code) or no history. Conditional logistic regression was used to estimate odds ratios (OR) and 95% CI for new-onset IBD, CD and UC. RESULTS:A total of 15 cases of IBD (10 CD, 4 UC, 1 IBD, type unclassified) with a prior history of bariatric surgery were identified. Most cases were women, had Roux-en-Y surgery years prior to diagnosis and few IBD-related complications. A total of 8980 cases and 43 059 controls were included in our database analysis. Adjusting for confounders, a past history of bariatric surgery was associated with an increased risk of new-onset IBD (OR 1.93, 95% CI 1.34-2.79). However, patients who had recent bariatric surgery did not appear to be at shorter term risk of IBD (OR 0.94, 95% CI 0.58-1.52). CONCLUSION/CONCLUSIONS:New-onset IBD was significantly associated with a past history of bariatric surgery. This potential association needs to be confirmed in future prospective studies.

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

The ileal pouch-anal anastomosis (IPAA) has become standard of care in maintaining fecal continence after colectomy. Elderly patients are able to undergo IPAA surgery safely with similar functional outcomes compared to those of younger patients. Overall, elderly patients with IPAA report satisfaction and high quality-of-life scores. When caring for the elderly patient with IPAA, many of the medications prescribed for management of pouchitis or diarrhea should be used with caution, with or without dose adjustments. Other special considerations in the elderly population include history or use of radiation therapy, dysplasia surveillance, and sphincter dysfunction.
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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: 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

Ileal pouch-anal anastomosis (IPAA) is the preferred surgical treatment for patients who undergo colectomy and wish to avoid a permanent ileostomy. The overall outcomes are positive, with an improved quality of life and stable long-term pouch retention. However, certain conditions or disease states may be at a higher risk of pouch dysfunction or failure. For example, obese patients have an increased risk for postoperative complications. In addition, women with a history of obstetric complications and elderly patients with a history of sphincter damage or dysfunction may be at an increased risk for postoperative incontinence, although quality-of-life indices do not necessarily correlate with incontinence scores. Advanced age itself is not a contraindication to pouch surgery, and elderly patients can be considered for IPAA based on individual functionality and comorbidities. Pelvic radiation may lead to pouch dysfunction. Finally, patients with Crohn's disease and indeterminate colitis may have increased complications with IPAA, but highly specific patient selection leads to good rates of pouch retention. This article examines several clinical scenarios that require careful thought prior to considering IPAA.

INTRODUCTION: As our medical armamentarium for IBD continues to expand, it is essential that clinicians understand both optimizing and sequencing of individual and combination therapeutic approaches with available medications. Areas covered: This review summarizes dosing strategies and therapeutic drug monitoring for pharmacologic optimization in IBD. Aminosalicylates remain first-line therapies for mild-to-moderate UC but have limited evidence of efficacy in CD. Budesonide provides an alternative to aminosalicylates when targeted to appropriate sites in the distal small bowel and colon, as do conventional corticosteroids when applied rectally. Systemic steroids are highly efficacious but burdened by toxicity. Thiopurines or methotrexate can be utilized as steroid-sparing agents. Biologic agents targeting TNF remain important for steroid-sparing therapy in moderate-to-severe UC and CD. Newer biologics targeting lymphocyte trafficking and lymphocyte activation are also efficacious for moderate-to-severe IBD. Near future conventional drug options include oral agents such as tofacitinib and mongersen. Expert commentary: Positioning therapies according to the location, phenotypes, and severity, as well as the use of therapeutic and clinical targets, will improve outcomes and minimize toxicities and therapeutic futilities. Future IBD treatment should focus on personalized therapy plans based on genetic determinants, targeted mechanisms of action, and pharmacologic optimization.

OPINION STATEMENT: Infliximab and adalimumab biosimilars have been approved by the FDA and European Medicines Agency and have already been introduced to the international market. Availability into the US market is imminent. Biosimilars are highly similar to the reference biologic product but should not be referred to as, nor equated with, generic medications as no two biosimilars can ever be identical. Regulatory pathways for biosimilar approval consider the totality of evidence for biosimilar approvals, but the preponderance of development relies on analytic and functional testing and allows extrapolation between indications to reduce the financial burden of completing comparative clinical trials for each indication. Neither CT-P13 (infliximab biosimilar) nor ABP 501 (adalimumab biosimilar) was clinically tested in patients with inflammatory bowel disease prior to being submitted for approval by regulatory agencies. The body of available evidence suggests that these drugs will perform similarly to their originators. The pathway for interchangeability of biosimilars has yet to be clarified by federal regulators and currently remains determined by states within the USA. However, preliminary data suggests that switching from originator to biosimilar is safe with minimal differences in clinical efficacy.