Faculty Bibliography

INTRODUCTION: Currently, endoscopic remission in ulcerative colitis (UC) is defined using the Mayo Endoscopic subscore (MES), with a score of 0 (normal mucosa) or 1 (erythema, decreased vascular pattern, mild friability) representing mucosal healing. However, it is not clear if clinical outcomes differ between patients with a MES of 0 and 1. The aim of our study was to evaluate differences in relapse rates between patients with MES of 0 and 1.
METHOD(S): UC patients who underwent colonoscopy at 2 IBD referral centers from 2012 to 2017 were identified. Inclusion criteria consisted of patients with a MES score of 0 or 1, no prior colectomy, and outpatient follow up for a minimum of 1 year after colonoscopy. Data was collected for demographics, disease characteristics, medications, time from last disease flare and inflammatory biomarkers. The primary outcome was defined as a composite of relapse requiring change in medical therapy, new steroid use, UC-related hospitalization, and colectomy. Chi Square, Fisher's exact and logistic regression modeling were used in statistical calculations.
RESULT(S): 446 UC patients were identified, with 228 (51%) and 218 (49%) having a MES of 0 and 1 respectively. 78% were Caucasian, 52% were female and mean age was 40 +/- 15 years. 20, 34, and 46% had proctitis, left sided colitis and extensive or pancolitis, respectively. 46% of patients were on either a 5-ASA alone or no medical therapy, while 46% were on biologics and 27% were on biologic therapy with an immune suppressant. Within 1 year from colonoscopy, 97 (22%) had a change in medical therapy and 66 (15%) were prescribed steroids. Only 8 and 4 patients were hospitalized for UC or underwent colectomy, respectively. UC patients with a MES of 1 were more likely to experience a relapse (P < 0.01) (Table 1). After adjusting for race, disease extent, and medication use, a MES of 1 was the only factor associated with an increased the risk of relapse (aOR 2.54, 1.61-4.01) (Table 2).
CONCLUSION(S): Patients with mild endoscopic activity by MES were at increased risk for relapse compared to patients with no endoscopic activity. In this population of UC patients, MES score was the only variable that predicted future relapse. Future studies are needed to classify low and high risk patients with mild endoscopic activity through evaluation of novel biomarkers and histology. Gastroenterologists should consider enhanced monitoring and/or changes in medical therapy based on the presence of even mild inflammation. (Figure Presented)

INTRODUCTION: Gut microbial dysbiosis and impaired mucosal immunity play a major role in the pathogenesis of inflammatory bowel disease (IBD). Previous research has shown that IBD patients experience greater disease burden from gastrointestinal infections. The increasing availability of gastrointestinal multiplex polymerase chain reaction stool panels (GI PCR) has allowed for the rapid and accurate identification of viral, bacterial, and parasitic pathogens not readily diagnosable with conventional stool testing. We aimed to characterize the burden and risk factors for gastrointestinal infections on outpatients with and without inflammatory bowel disease presenting with symptoms of acute gastroenteritis.
METHOD(S): We performed a cross-sectional review of outpatients presenting with gastroenteritis to an academic medical center from September 2015 to March 2019 who received a FilmArray GI PCR. Baseline demographics, presence of IBD and disease characteristics, risk factors including travel history, sexual activity, HIV status, and symptoms on initial presentation were recorded. The primary outcome was the detection of an enteric pathogen. Secondary outcomes include the class of pathogen detected, i.e., viral, bacterial, parasitic. T-test and Chi-square analysis were used to compare outcomes between groups.
RESULT(S): We reviewed 815 outpatients who received GI PCR testing, of whom 94 (12%) were diagnosed with IBD. Patients with IBD were more likely to present to the initial visit with bloody diarrhea (46% vs. 8%, P < 0.001), hematochezia (15% vs. 6%, P = 0.001), and fever (23% vs. 9%, P < 0.001; Table 1). Of outpatients with IBD, 33 (35%) had a gastrointestinal pathogen detected compared to 216 (30%, P = 0.190) of non-IBD outpatients. Patients with IBD were more likely to have viral (28% vs. 18%, P = 0.044) or multiple pathogens (11% vs. 6%, P = 0.028) and less likely to have bacterial (61% vs. 73%, P = 0.920) and parasitic infections (0 vs. 6%, P = 0.382) on GI PCR (Table 2). There were no statistically significant differences in gender, race, travel history, sexual activity, HIV status, or rate of pathogen detection between patients with and without IBD.
CONCLUSION(S): Enteric infections were common in outpatients with and without IBD. IBD patients presented with more viral and multiple pathogens on GI PCR testing compared to non-IBD controls. Further studies are needed to investigate the impact of these different enteric pathogens on clinical management and disease burden. (Figure Presented)

Background/Purpose : Prevalence of sacroiliitis (SI) in Crohn's disease (CD) varies widely (range 4% -39%), depending on criteria utilized to define the disease (e.g. inflammatory back pain, plain radiographs or MRI). Sacroiliitis may remain underdiagnosed in CD patients given lack of association with clinical symptoms of back pain and CD activity. However, patients with CD often undergo magnetic resonance enterography (MRE) to assess extent, severity of small bowel CD and radiographic healing, affording clinicians the opportunity to evaluate for the presence of active and/or chronic SI. We sought to identify the prevalence of sacroiliitis in CD patients utilizing MRE and determine its relationship with CD activity, especially with concurrent biologic therapy. Methods : All CD subjects undergoing MRE between years 2014-2018 at a large IBD referral center were identified. A musculoskeletal radiologist, blinded to clinical data, reviewed all MRE exams for the presence of acute bone marrow edema (BME) lesions and chronic lesions suggestive of acute and chronic SI, respectively. A second radiologist, also blinded, assessed MRE for mucosal CD activity using validated measures. Charts were reviewed for demographics, IBD characteristics, presence of back pain, clinical and endoscopic activity of CD, and Crohn's therapies within 3 months of MRE. Comparisons were made between CD subjects with and without SI using chi-square test. Univariate and multivariate logistic regression were used to determine risk factors of SI. Results : 258 subjects with CD underwent MRE during the study period with a mean age of 35 years old, 53% (n=138) were male, and mean duration of CD at the time of MRE was 9 years. Few reported back pain (8%) and 14% had previously seen a rheumatologist. Overall, 17% (n=45) of patients had MR evidence of sacroiliitis (Table 1). Female gender, presence of back pain, and later age of CD diagnosis were associated with signs of sacroiliitis (p=0.05, p< 0.001, p=0.04 respectively; Table 2). Stricturing phenotype was associated with a lower rate of SI (7% vs. 24%; p=0.018), but inflammatory or penetrating phenotypes were not. CD location, activity as noted by clinical scores, endoscopic disease activity, or radiographic disease activity on MRE, were not associated with sacroiliitis (Table 2). On multivariable analysis, back pain was associated with the presence of sacroiliitis on MRE (OR 3.0, 95% CI 1.1-5.6; p=0.04). Concurrent CD therapy with biologics did not lower the risk of sacroiliitis. Conclusion : Although often underdiagnosed, SI is a common comorbid condition in CD. While recent history of back pain was associated with the presence of sacroiliitis visualized on MRE, no correlations were found with other clinical and endoscopic markers of CD activity. Moreover, concurrent CD therapy, especially biologics, was not associated with a lower risk of sacroiliitis on MRE. With limited clinical clues and CD characteristics to suggest sacroiliitis, gastroenterologists can utilize MRE as a screening tool to detect SI and refer CD patients to rheumatologists. Presence of SI on MRE in CD patients with back pain may help identify a subset of individuals likely to benefit from switching to therapies with proven efficacy in axial SpA

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