bluuebunny/crossref_metadata_2025 huggingface dataset:
613 Comparison of Clinical Outcomes in Traditional Gastrointestinal Hemorrhage Work-Up Versus Direct Utilization by Push Enteroscopy in Patients With a Left Ventricular Assist Device
Authors: Ghanimeh Mouhanna Abu , Hassan Seemeen , Mazhar Areej , Naffouj Sandra , Isseh Mahmoud , Abuamr Khalil , Kutait Anas , Bkumenkehl Mark
Published: October 2019

INTRODUCTION:

Patients with left ventricular assisted devices (LVADs) are at considerable risk of gastrointestinal bleeding (GIB) of about 23%. A significant portion of GIB occur in the stomach, duodenum or small intestine as compared with lower intestinal tract. The traditional workup for such patients usually starts with an EGD ± colonoscopy, then proceeds with a small bowel evaluation if the initial workup is negative. This approach requires considerable time and effort which may lead to longer hospitalizations and multiple procedures. Our goal is to compare the traditional work up GIB with an innovative approach of performing push enteroscopy (PE) as the first diagnostic/therapeutic procedure.

METHODS:

This is a retrospective study was performed in Henry Ford Hospital in Detroit, MI. ICD-9 and ICD-10 diagnosis codes were used to generate a list of LVAD patients who were admitted with an overt GIB or worsening anemia in the period from 1/1/2013 to 12/25/2018. Our primary outcomes were the rate of detection of GIB lesion and all-cause mortality. Secondary outcome was the length of hospitalization.

RESULTS:

A total of 227 patients were reviewed. 89 patients were included (Mean age 61.36 years old, 75.28% were males). Most patients presented with either melena or worsening anemia without overt GIB. A total of 71 patients underwent the traditional approach at the first index endoscopy, whereas 18 patients started with PE ± colonoscopy. The source of GIB was detected at the first index endoscopy in 51 patients (36 traditional approach and 15 in PE approach). Arteriovenous malformation was the most common lesion detected and the two most common sites of bleeding were gastroduodenal followed by the small bowel. The PE approach was associated with a higher rate of GI site detection, OR 4.861 (95% CI (1.293-18.271), P 0.012), this was true, especially when patients presented with worsening anemia without overt bleeding, OR 11.2 (95% CI (1.202-104.33), P 0.015). There was no statistically significant difference between both approaches in terms of all-cause mortality (P 0.163). Patients in the PE approach did have a shorter hospital stay (x̅ (SD) 10.78 (13.97) days compared to 18.8 (25.58) days for the traditional approach) with P 0.034.

CONCLUSION:

PE is a safe procedure. It increases the GIB site detection and shortens the length of hospital stay when considered on the initial evaluation of LVAD patients presenting with GIB in general and worsening anemia in specific.
615 GI Bleeding, Risk Factors and Predictors of Endoscopic Evaluation and Severe Complicated Course
Authors: Bella Saif , Hoilat Judie , Alom Md S. , Saleem Atif , Hila Amine
Published: October 2019

INTRODUCTION:

Acute gastrointestinal (GI) bleeding is a common worldwide clinical problem and continues to be associated with significant morbidity, hospital admission, and mortality. Overall, for patients hospitalized for GI bleeding, 40% occurred in the UGI tract, 25% in the LGI tract and 35% in an undefined location (1). Clinical presentation and outcomes vary. Bleeding from the GI tract is usually mild, self-limited, and the majority heal spontaneously. However, massive hemorrhage can happen. We aim to identify risk factors that predict the need for endoscopy or a complicated hospital course.

METHODS:

This is a retrospective study. We reviewed adult patients who were admitted with GI bleeding diagnosis from 10/2017-10/2018. We looked for risks and predictors of primary and secondary outcomes. The primary outcome was defined as the need for endoscopic evaluation (EGD or colonoscopy) within 14 days of admission. Secondary outcomes: 30-day hospital readmission and complicated course. A complicated course was defined with any of the following: ICU admission; Blood transfusion; increase the length of stay (7 days or more) and need for surgical intervention or death.

RESULTS:

Preliminary analysis was performed. A total of 148 patients were reviewed with a mean age of 70 years old. 56% of patients were females. Hemoglobin <8 g/dl, melena and bright red blood per rectum were significantly associated with an increasing need for endoscopic evaluation (Table 1). No significant association between patient age, gender, Obesity, and abnormal systemic inflammatory response indicators and the need for endoscopic evaluation. History of CHF, history of blood thinner use (Aspirin, Plavix, Ticagrelor, Warfarin or NOACs), presentation of exertional dyspnea, weakness, hemoglobin <8 g/dl, PT >15 sec, WBC >12K, Albumin <3 g/dl, SBP <90 mmHg and CRP >1 mg/L were significantly associated with an increase in the length of stay and complicated course (Figure).

CONCLUSION:

A comprehensive triage is important in evaluating patients presenting with GI bleeding. Predictors of poor outcome in such patients can be extracted from history, physical examination, vital signs, and initial lab workup. This may help to give priority to high-risk patients and planning for safe discharge and follow up.
621 Utility of FIT Testing in an Inpatient Setting
Authors: Barsky Maria , Nguyen Amie , Leverone Nicholas , Seav Susan , Losli Mathew , Solanky Dipesh , Saymann Gregory
Published: October 2019

INTRODUCTION:

Fecal immunochemical tests (FITs) measure the globin portion of human hemoglobin and have been validated for the use of colorectal cancer screening. FIT testing is associated with many false positive (type I errors) due to GI inflammation, certain medications and even some foods. Furthermore, studies show that FIT testing often has little to no impact on clinical decision making in the hospital setting. Many argue the test adds cost and risk without providing meaningful clinical value in the inpatient setting.

METHODS:

The Slicer-Dicer tool of the EPIC electronic medical record system was used to identify patients hospitalized at UC San Diego affiliated hospitals between January and July 2018 who had a FIT test ordered. The primary outcome was proportion of patients with positive FIT testing receiving endoscopy. Secondary outcomes included reason for ordering FIT testing, proportion of patients referred for endoscopy at discharge, proportion of patients completing endoscopy after outpatient referral, and proportion of patients diagnosed with colon cancer on outpatient colonoscopy. Patient excluded were those who died during admission.

RESULTS:

During the 6 month study period, 140 inpatient FIT tests were ordered and 76 (54.3%) were positive. The majority of tests were ordered by the internal medicine service (Figure 1). Anemia was the leading indication for ordering the test (60% of all cases). 21% of the tests were ordered despite documented melena/hematochezia, and 70% of these tests were positive. Among the 76 patients with positive tests, 27 (36%) underwent inpatient EGD, 21 (28%) underwent inpatient colonoscopy, and 14 (18%) had both. Most patients with positive FIT testing did not receive an inpatient colonoscopy (72%, n = 55), and 42 (55.3%) did not receive any endoscopic testing. Of those 55 patients with positive FIT testing that did not receive inpatient colonoscopy, 26 (47%) did receive an outpatient GI referral, but only 8 (15%) received a colonoscopy within 6 months of discharge. No colon cancer was diagnosed in this small cohort. Among the 76 patients with positive inpatient FIT tests, 29 (38%) had neither GI referral nor endoscopy performed.

CONCLUSION:

Inappropriate use of FIT testing was prevalent at our institution, with inadequate documented follow up of abnormal testing in over one third of patients. Inadequate follow up can potentially lead to missed diagnoses of colon cancer.
622 Economic Burden of Bleeding Gastrointestinal Angioectasias
Authors: Baumgartner William , Stibbe Jason R. , Raines Daniel , Jiang Wei
Published: October 2019

INTRODUCTION:

Angioectasias are dilated, thin-walled blood vessels resulting from degenerative changes in capillary vascular structure. They can occur anywhere within the gastrointestinal tract and are the most common source of small intestinal bleeding in patients over age 50. Small bowel angioectasias have the highest re-bleeding rates when compared to other sources. It is assumed that angioectasias complicated by bleeding result in consumption of a large volume of medical resources but this consumption has not yet be quantified in the medical literature.

METHODS:

A retrospective cross-sectional study was performed using Medicare data base analysis of ICD-10-DM codes for patients diagnosed with anemia and/or gastrointestinal hemorrhage during 2016 and 2017. A Crosswalk analysis of ICD-10-DM codes pertaining to primary gastrointestinal bleeding and primary anemia from angioectasias converted these codes into corresponding DRG (inpatient) and CPT (outpatient) codes. These codes of interest were followed throughout 2016 and 2017 in order to determine the cost of medical care for symptomatic angioectasias.

RESULTS:

In 2016, 38,250 Medicare services were provided in the management of angioectasias at a total cost of roughly $240 million. Hospitalizations accounted for 48% of total service volume but 95% of total costs at an average expense of $12,391 per inpatient stay. Outpatient services accounted for 52% of all services provided but only 5% of total annual costs in this analysis. Average costs for individual outpatient services were broken down into categories of therapeutic endoscopy ($922), diagnostic endoscopy ($805), injections ($522), blood transfusions ($261), and outpatient clinic visits ($261). Therapeutic endoscopy was the most expensive outpatient service category, accounting for 64% of all outpatient costs. A separate analysis of 2017 Medicare data validated our findings from the previous year with a steady total cost and only slightly (5%) increase in volume of individual services.

CONCLUSION:

Angioectasias are a common source of gastrointestinal bleeding and are associated with high recurrence rates as well as substantial morbidity. This study confirms that a large volume of medical resources are consumed in that management of bleeding angioectasias. In recognition of these findings, additional research is justified to improve upon our understanding and management of this disease process.
625 Characteristics of Patients With Obscure Gastrointestinal Bleeding in an Urban Academic Center
Authors: Hengehold Tricia A. , Li Lezhi , Yacyshyn Bruce
Published: October 2019

INTRODUCTION:

Gastrointestinal bleeding is a significant clinical problem accounting annually for over 500,000 hospital admissions and 840,000 emergency room visits (1). Intestinal angioectasia (AEC) are an important cause of this bleeding, however, there is a lack of knowledge about this population's demographics. Aortic valve disease (Heyde's syndrome) and hereditary hemorrhagic telangiectasia (HHT) have been the most established etiologies and do not account for the majority of cases or increasing incidence. We sought to identify characteristics of patients with AEC, a condition increasing in incidence.

METHODS:

One urban academic center's electronic medical record was searched using ICD 9 and 10 codes to identify patients with gastrointestinal AEC. Those with aortic valve disease and HHT were removed. The control group included only those ages 65 and older. Demographic information was collected (age, gender, race, insurance and body mass index (BMI)), and the groups were further broken down into BMI >30 and BMI <30. The presence of diabetes mellitus (DM), chronic kidney disease (CKD), and diverticular disease was found.

RESULTS:

There was a total of 835 patients in the AEC cohort (average age of 65) that were compared to a control population of 318,923. More patients had a BMI >30 when compared to control (37.89% v 33.57%, P = 0.009). Additionally, the AEC cohort had more patients with DM (42.99% v 9.04%, and 20.87%, P < 0.001), CKD (35.21% v 5.00% and 11.72%, P < 0.001), and diverticular disease (36.89% v 2.85% and 6.78%, P < 0.001) than the total control and the control group with known BMIs. Demographics were similar between groups in the categories of gender, types of insurance and race. However, the AEC cohort had more patients that identified as black (30.74% v 11.16%, P < 0.001).

CONCLUSION:

Clinically, the increasing incidence of obscure gastrointestinal bleeding due to AEC is due to the increasing prevalence of complex chronic diseases that contribute to this condition. Our results showed that CKD and older age are risk factors. Additionally, we found that a BMI > 30 and DM are associated with a higher incidence of AEC. Diverticular disease was found to be a co-existing condition. Recognizing these risks and associated diseases is necessary to decrease the risk of bleeding from AEC, which can be very difficult to manage clinically with risk of significant morbidity and economic impact to healthcare.
632 Hemospray Efficacy in Achieving Immediate Hemostasis in Monotherapy versus Salvage Therapy: A Meta-Analysis
Authors: Odah Tarek , Ghoz Hassan
Published: October 2019

INTRODUCTION:

The U.S. Food and Drug Administration (FDA) has recently approved the Hemospray (Cook Medical, Winston-Salem, North Carolina, USA) for treatment of gastrointestinal bleeding. Hemospray can be used as a monotherapy in certain circumstances and as salvage therapy in others. In this analysis, we compare the immediate hemostasis effects of Hemospray in upper gastrointestinal bleeding when used as a monotherapy compared to when used as a salvage treatment after failure of conventional hemostatic measures.

METHODS:

An extensive search for available studies comparing hemostasis effects of Hemospray as monotherapy versus salvage therapy in the treatment of upper gastrointestinal bleeding was performed in MEDLINE and Google scholar engine. Twenty-two studies were included. Odds ratios were calculated. Pooled odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using either the fixed-effects or random-effects model.

RESULTS:

A total of 489 patients were included and divided into two groups, monotherapy group (N = 267 patients) and salvage group (N = 222 patients). A pooled odds ratio of 0.72 (95% confidence interval CI 0.27-1.92, P = 0.86) was obtained between two groups. Moreover, immediate hemostasis was achieved in 94% and 96.8% for monotherapy and salvage therapy, respectively.

CONCLUSION:

Both monotherapy and salvage therapies were highly effective in achieving immediate hemostasis in upper gastrointestinal bleeding.
635 Peripartum Exposure to Biologic Therapy Does Not Impact Wound Healing After Cesarean Section in Women With Inflammatory Bowel Disease
Authors: Aboubakr Aiya , Riggs Alexa , Mella Maria , Dubinsky Marla C.
Published: October 2019

INTRODUCTION:

Inflammatory bowel disease (IBD) commonly affects women during their childbearing years, and mode of delivery is a frequent topic of concern. Rates of Cesarean section (C-section) are increased in women with IBD. Biologics are commonly used during pregnancy and data on their effect on C-section outcomes are limited. We investigated whether exposure to biologic agents impacts wound healing after C-section in women with IBD.

METHODS:

Women with IBD seeking consultation at the Marie and Barry Lipman IBD Preconception and Pregnancy Planning (I-PrePP) Clinic between years 2015-2019 were eligible. Delivery data collected as part of the I-PrePP prospective registry were analyzed. Primary outcome was rate of surgical site infection prior to discharge and/or at follow-up visits 2 and 6 weeks after delivery. Timing of biologics were investigated as well as impact of steroids on wound healing. Descriptive statistics summarized patient level data using frequency for categorical variables and median [IQR] for continuous.

RESULTS:

Of the 84 women who presented or became pregnant after their I-PrePP consultation, delivery data was available from 64 (38 (59%) Crohn's disease, 24 (38%) ulcerative colitis, 2 IBD-U (3%)) pregnancies (median [IQR] age 33 [29-35] years). Indications for the 37 C-sections (58%) included: history of perianal disease (n = 12, 32%), severely active inflammation (n = 1, 3%), ileal pouch anal anastomosis or end ileostomy (n = 2, 5%), previous C-section (n = 7, 19%), other obstetrical indications (large for gestational age, arrest of labor, malpresentation) (n = 14, 38%), or other (n = 1, 3%). Twenty six of 37 (70%) women with C-sections were exposed to biologics during pregnancy: infliximab (n = 13, 35%), adalimumab (n = 5, 14%), ustekinumab (n = 3, 8%), vedolizumab (n = 4, 11%), and certolizumab (n = 1, 3%). Time from last dose to delivery was 6 [4-7] weeks, and 21 of 26 (81%) received therapy at the time of (n = 10) and/or within 2 weeks (n = 11) of delivery. Four (11%) were exposed to systemic steroid therapy, including 2 patients at the time of and/or within 2 weeks of delivery. There was no incidence of surgical site infection in the biologic exposed patients, 1 case of MRSA bacteremia with an intra-abdominal abscess in a patient on systemic steroids, and 1 superficial infection in a non-medicated patient.

CONCLUSION:

Our data suggests that biologics exposure in the peripartum period does not adversely affect wound healing after cesarean section in women with IBD.
640 Outcomes in Geriatric Patients Admitted for IBD Management: A National Study
Authors: Schwartz Jeffrey , Li Brian , Stein Daniel J. , Feuerstein Joseph
Published: October 2019

INTRODUCTION:

The proportion of the population considered geriatric continues to rise in the United States, as well as in most of the developed world. Based on this trend, combined with increased prevalence of inflammatory bowel disease (IBD), the burden of caring for elderly patients with IBD will likely rise. Given the complications of hospitalization in this cohort, we set to examine if elderly patients age >75 were at higher risk of poor outcomes when admitted for their IBD.

METHODS:

This national inpatient sample (NIS) from 2016 (most recent available) was queried for all cases of Crohn's or ulcerative colitis (UC) where this was the principle cause for admission (first diagnosis code) based on ICD-10. Outcomes for patients age >75 were compared to those <75 using survey-adjusted logistic/linear regression to examine mortality, length of stay, and hospitalization costs. Adjustment was made for the Elixahauser mortality score (a validated measure of comorbidities), undergoing surgery during the admission, and the presence of C diff infection. Crohn's and UC were analyzed separately.

RESULTS:

In 2016, admissions for UC were 35,950 and for Crohn's were 71,040. In UC, 1.4% of geriatric vs 0.2% of non-geriatric patients died in the hospital (P < 0.001). Similar results were found in Crohn's at 1.0% versus 0.1% (P < 0.001). Average Elixhauser mortality index (a validated measure of comorbidities) was higher for geriatric patients for UC (8.4 vs 4.8, P < 0.001) and Crohn's (7.3 vs 3.3, P < 0.001). In the regression analysis for Crohn's, non-geriatric patients had a OR = 0.25 of death (P = 0.001) but no significant difference in length of stay (P = 0.119) or costs (P = 0.446). For the UC regression, similar findings of an OR = 0.19 of death (P < 0.001) but no change in LOS (P = 0.529) or costs (P = 0.927) were seen. For all admissions in NIS, an OR = 0.50 was seen for the same controlling variables.

CONCLUSION:

In this U.S. national cohort from 2016, age >75 was associated with a notably higher odds of death in both UC and Crohn's patients, with nearly four times the odds of inpatient mortality even after adjustment for comorbidities. This is more than double the mortality difference compared to non-IBD admissions. Further research is needed to customize care for this growing group of individuals to improve outcomes.
643 RHB-104, a Fixed-Dose, Oral Antibiotic Combination Against Mycobacterium Avium Paratuberculosis (MAP) Infection, Is Effective in Moderately to Severely Active Crohn's Disease
Authors: Graham David Y. , Naser Saleh A. , Offman Elliot , Kassir Nastya , Hardi Robert , Welton Thomas , Rydzewska Grazyna , Stepien Beata , Arlukowicz Tomasz , Wos Anna , Fehrmann Clara , Anderson Patricia , Bibliowicz Aida , McLean Patrick , Fathi Reza , Harris M. Scott , Kalfus Ira N.
Published: October 2019

INTRODUCTION:

MAP US was a global multicenter randomized trial comparing the efficacy and safety of RHB-104, a fixed-dose oral combination of clarithromycin, rifabutin and clofazimine against MAP infection, in moderately to severely active Crohn's disease (CD). We report evaluations of efficacy, symptom improvement and exposure-response by individual RHB-104 components.

METHODS:

Patients with active CD (CDAI ≥220 and ≤450) and failure with conventional therapies were randomized 1:1 to RHB-104 or placebo for up to 52 Wks. Concomitant corticosteroids, immunosuppressives (IS) and anti-TNF agents were permitted. The primary endpoint was clinical remission (CDAI <150) at Wk 26. Secondary endpoints included clinical response at Wk 26 (CDAI decrease ≥100 points), early remission at Wk 16 and remission at Wk 52. A population pharmacokinetic (PK) and exposure-response analysis was performed based on PK assessments and remission at Wk 26; a subset of patients underwent colonoscopy at baseline and Wk 26.

RESULTS:

331 subjects were randomized at 92 sites. The proportion achieving remission at Wk 26 (36.7% vs 23%, P = .007), remission at Wk 16 (42.2% vs 29.1%, P = .015) and response at Wk 26 (44% vs 30.9%, P = .017) were significantly greater with RHB-104 vs placebo. The superiority of RHB-104 was more pronounced in patients receiving RHB-104 with concomitant anti-TNF or IS treatment. Despite the small numbers (n = 35), a greater proportion of RHB-104 patients achieved endoscopic response by SES-CD 50 (28.6% vs 4.8%, P = .11). Differences in fecal calprotectin (FCP) increased over time (Figure 1); improvements in PRO-2 symptoms appeared by Wk 4 and reached significance by Wk 16 (Figure 2). A significantly greater proportion of patients receiving RHB-104 achieved clinical remission with at least a 50% reduction from baseline in either FCP or CRP concentration at Wk 16 (25.9% vs 9.7%, P = .0002), Wk 26 (21.1% vs 9.1%, P = .0003) and Wk 52 (16.9% vs 7.9%, P = .02). Exposure-response modeling demonstrated the combination of the individual components of RHB-104 contributed to the higher rate of remission compared to placebo and that the probability of achieving remission was most sensitive to clofazimine.

CONCLUSION:

RHB-104 demonstrated meaningful improvement in efficacy and biomarkers of active inflammation, with exposure-response for each drug component, early onset of response and benefit in patients with and without concomitant anti-TNF or IS therapy.
645 Black and White Patients With Inflammatory Bowel Disease Demonstrate Similar Biologic Use Patterns With Medicaid Insurance
Authors: Barnes Edward L. , Sandler Robert , Kappelman Michael , Long Millie D.
Published: October 2019

INTRODUCTION:

Prior studies have indicated that significant disparities exist when comparing black and white patients with inflammatory bowel disease (IBD), including increased emergency department visits and difficulty accessing specialists for Crohn's disease (CD) and ulcerative colitis (UC). The primary objective of this study was to compare any use of IBD-specific therapies among black and white patients with Medicaid Insurance, where race is self-reported at enrollment and patients have uniform insurance coverage. Among patients with CD who underwent surgery, we also aimed to evaluate postoperative therapies.

METHODS:

We performed a retrospective cohort study, analyzing data from the Medicaid Analytic Extract from four states (CA, GA, NC, and TX) between 2007 and 2014. We compared the use of IBD-specific therapies between black and white patients with IBD, including specific analyses of postoperative therapy among patients with CD. We performed bivariate analyses and multivariable logistic regression, adjusting for potential confounders.

RESULTS:

We identified 14,735 patients with IBD [4,672 black race (32%), 8,277 CD (58%)]. Among all 14,375 patients, 64% received at least one IBD-specific medication. Black patients were significantly more likely to receive therapy with an immunomodulator (20% vs. 15%, P < 0.001), an anti-tumor necrosis alpha (anti-TNF) therapy (23% vs. 18%, P < 0.001), combination therapy with an anti-TNF and an immunomodulator (4% vs. 3%, P < 0.001) and prednisone (43% vs. 38%, P < 0.001, Table 1). In multivariable analysis, there was no significant difference in odds of anti-TNF use by race for CD [adjusted Odds Ratio (aOR) 1.13, 95% Confidence Interval (CI): 0.99-1.28] or UC (aOR 1.12, 95% CI: 0.96-1.32, Table 2). Black patients with CD were more likely to receive combination therapy (aOR 1.50, 95% CI: 1.15-1.96). Among 398 patients undergoing surgery for CD, black patients received earlier postoperative therapy with an anti-TNF (median 94 days vs. 132 days, P = 0.023) and azathioprine (median 53 days vs. 92 days, P = 0.024), with no significant difference noted in use of methotrexate in the post-operative period.

CONCLUSION:

In patients with Medicaid Insurance, where access to IBD-specific therapy should be similar for all individuals, there was no significant disparity by race in the utilization of IBD-specific therapies. Access to comparable insurance benefits may aid significantly in resolving apparent healthcare disparities.
649 Multiplex Polymerase Chain Reaction-Based Stool Testing Results in Less Endoscopy in Outpatients With Inflammatory Bowel Disease Compared to Conventional Stool Testing
Authors: Hong Soonwook , Hine Ashley M. , Main Michael , Hudesman David P. , Chang Shannon , Axelrad Jordan E.
Published: October 2019

INTRODUCTION:

Patients with inflammatory bowel disease (IBD) frequently receive stool testing for exacerbations in gastrointestinal symptoms. Multiplex polymerase chain reaction-based gastrointestinal pathogen panels (GI PCR) offer significant benefits in sensitivity over conventional tests such as culture and ova and parasites exam. However, it is unclear how additional pathogen positive findings by GI PCR affect further clinical management. In this study we compared the downstream healthcare utilization of IBD patients who received GI PCR to conventional stool testing.

METHODS:

We reviewed outpatients presenting to an academic medical center with an acute episode of diarrhea from September 2015 to February 2019 to identify patients with IBD who received stool testing with a FilmArray GI PCR or stool culture and ova and parasite exam (conventional testing). All patients received isolated PCR testing for Clostridium difficile. Each GI PCR patient was randomly matched with a conventional testing patient based on age, sex, and date of testing. Post-visit endoscopy, abdominal radiology, antibiotic therapy, and escalation in IBD medical therapy defined as an increase in the dose of a prior medication or prescription of a new medication were recorded. Long-term outcomes including emergency room (ER) visits, hospitalizations, and abdominal surgery were recorded as well. T-test and Chi-square analysis were used to compare outcomes between groups.

RESULTS:

Among 1,104 patients receiving stool testing, we identified 120 outpatients with IBD, of whom 26 (22%) received conventional stool testing and 94 (78%) GI PCR testing. Of 26 patients with conventional testing, 1 (4%) had a pathogen identified on testing while 36 (38%) of 94 GI PCR patients had positive tests (Table 2). There were no significant differences in demographics, IBD characteristics, rates of C. difficile infection, and behavioral risk factors between groups (P > 0.05). GI PCR patients were less likely to receive any endoscopic exam in the 30-day period after their initial visit (20% vs. 42%, P = 0.021). There were no significant differences in exposure to radiology, antibiotics, escalation of IBD therapy, or long-term IBD outcomes (P > 0.05).

CONCLUSION:

Testing with GI PCR was associated with lower rates of post-visit endoscopywith no differences in long-term outcomes in outpatients with IBD. This study suggests that in certain populations of patients, GI PCR testing has the potential to reduce downstream healthcare utilization and management burden.
656 Ustekinumab Dose Escalation Is Effective in Treatment of Crohn's Disease
Authors: Cohen Erica , Ha Christina , Syal Gaurav
Published: October 2019

INTRODUCTION:

Ustekinumab (UST) is approved for moderate to severe Crohn's disease (CD) at 90 mg every 8 week dose for maintenance. However, there is limited data about the benefit of UST dose escalation. The aim of this study was to evaluate the response to UST dose escalation in a real-world cohort of active CD patients.

METHODS:

CD patients who had partial or no clinical response to standard UST induction and/or maintenance and required dose escalation to 90 mg every 4 or 6 weeks from 2016 to 2018 at a tertiary IBD referral center were retrospectively identified. Patients who did not receive UST intravenous induction dose or had clinically inactive disease at the time of dose escalation were excluded. Response and remission were defined based on physician global assessment. Primary outcome was clinical response to dose escalation. Secondary outcomes were clinical remission and endoscopic response to dose escalation. Multivariable regression with backward elimination was performed to identify predictors of clinical response to UST dose escalation.

RESULTS:

A total of 68 patients received UST dose escalation, median age of the cohort was 39 years, 56% of patients were females. The majority (51.5%) had ileocolonic disease. 57.4% had stricturing disease, and 39.7% had non-stricturing non-penetrating disease. 54.4% had a prior surgical resection. Prior medication exposure included: immunomodulators (78%), anti-TNF (95.3%) and anti-integrin drugs (46.9%). Overall, 67.8% of patients had clinical response at week 8 after UST induction dose. Following UST dose escalation, 79.4% of patients had a clinical response and 30.9% achieved clinical remission within 3-6 months. Of the patients with available endoscopic follow-up data (n = 39), 59% had endoscopic response, and 20.5% achieved endoscopic remission. Baseline characteristics between responders and non-responders to UST dose escalation were similar except for a higher proportion of responders having had clinical response to UST induction dose (Table 1). On multivariable regression analysis, response to UST induction therapy was the only independent predictor of response to UST dose escalation (OR 7.01; 95% CI 1.83-27.07; P = 0.005).

CONCLUSION:

A majority of patients with moderate to severe CD benefited from UST dose escalation suggesting the clinical utility of optimizing dosing in the treatment course. Response to UST induction dose may be a strong predictor of subsequent response to UST dose escalation.
671 An Update on the Analysis of Non-Melanoma Skin Cancer in the Tofacitinib Ulcerative Colitis Program
Authors: Sands Bruce E. , Long Millie D. , Baidoo Leonard , Reinisch Walter , Panés Julian , Soonasra Arif , Pedersen Ronald D. , Lawendy Nervin , Chan Gary
Published: October 2019

INTRODUCTION:

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). We present an updated integrated analysis of non-melanoma skin cancer (NMSC) events in the tofacitinib UC clinical program as of Sep 2018.

METHODS:

NMSC events were evaluated from 4 randomized, placebo-controlled studies (Phase [P] 2 and P3 induction studies [NCT00787202; NCT01465763; NCT01458951], a maintenance P3 study [NCT01458574]), and an ongoing, open-label, long-term extension (OLE) study (NCT01470612).
1–3
Three cohorts were analyzed: Induction (P2/P3 induction studies); Maintenance (P3 maintenance study); Overall (patients [pts] receiving ≥1 dose of tofacitinib 5 or 10 mg twice daily [BID] in P2, P3, or ongoing OLE studies). For P3 studies, a blinded independent adjudication committee reviewed potential NMSC. Proportions and incidence rates (IRs; unique pts with events per 100 pt-years [PY] of exposure) for NMSC were evaluated. A Cox proportional hazards model was used for risk factor analysis.

RESULTS:

1124 pts were evaluated for NMSC (P3 studies only), with 2399 PY of tofacitinib exposure and up to 6.1 years of treatment. NMSC occurred in 2 Induction tofacitinib-treated pts, 1 Maintenance placebo-treated pt (IR 0.97), 3 Maintenance 10 mg BID pts (IR 1.91), and 19 Overall Cohort pts (IR 0.78). 10 pts had squamous cell carcinoma (SCC) and 12 pts had basal cell carcinoma (BCC); 3 pts had both SCC and BCC (Table). No NMSC was metastatic or led to discontinuation. The Overall Cohort showed higher IRs for pts aged ≥50 years vs other subgroups and for pts with prior tumor necrosis factor inhibitor treatment, or prior immunosuppressant use vs those without (Table 1). Prior NMSC (hazard ratio [HR] 10.95; 95% CI 3.72, 32.24; P < 0.0001) and age (HR per 10-year increase 2.10; 95% CI 1.41, 3.13; P = 0.0003) were significant risk factors for NMSC.

CONCLUSION:

NMSC events were infrequent in the tofacitinib UC program, and were more likely to occur in pts with prior NMSC, and with increasing age – known NMSC risk factors.
4
NMSC IRs were similar to those reported for tofacitinib in rheumatoid arthritis
5
and for biologic UC treatments.
6
675 Measuring Serum Vedolizumab and Antibodies to Vedolizumab: Comparison of Four Commercially Available Clinical Laboratory Assays to the Assay Used in Vedolizumab Development
Authors: Yang Lili , Dobler Iwona , Agboton Christian , Osborn Teresa , Smithson Glennda
Published: October 2019

INTRODUCTION:

Vedolizumab (VDZ), a monoclonal antibody targeting the α4β7 integrin, is approved for the treatment of inflammatory bowel disease (IBD). Treatment optimization with VDZ may be informed by measuring VDZ serum levels. However, the assays used in the GEMINI studies are not commercially available and the relationship to results obtained with commercial assays is unknown. Therefore, VDZ serum level and anti-VDZ antibody (AVA) assays from Grifols Diagnostic Solutions, Immundiagnostik AG, Progenika Biopharma and Theradiag were compared to the assays used by Takeda (Reference; Ref).

METHODS:

The following identical sample sets were provided for serum level analysis: 1) 10 pooled sample groups (in triplicate) from biologic-naïve IBD patients spiked with up to 70 mg/mL of VDZ, 2) 2 pooled sample groups (in duplicate) biologic-naive subjects, both groups had a combination of 10 mg/mL infliximab (IFX) and 5 mg/mL of adalimumab (ADA), one group with 20 mg/mL VDZ and a second group without VDZ. 3) 23 singlet samples from VDZ-treated IBD patients with free drug concentrations between 8-60 mg/mL. 4) For AVA, 8 singlet samples with AVA (0 - ≥ 0.5 mg/mL), 4 with 15 mg/mL of VDZ and 4 without VDZ. For VDZ-spiked groups 1 and 2, results for replicates were averaged and were compared to the Ref assay results. Slopes were calculated by weighted least squares regression (spiked samples) or by linear regression (patient samples). AVA was detected with a qualitative assay, with results reported as AVA positive or AVA negative.

RESULTS:

All assays were specific with no cross-reactivity with IFX or ADA and were selective, detecting VDZ in samples that were spiked with all three drugs. Overall Vendor analysis of spiked samples correlated well (R2 ≥ 0.90) with the Ref assay but there were differences in the measured values based on differing slopes (range 0.94-1.56). Likewise, vendor patient sample analysis correlated well with the Ref assay (R2 ≥ 0.95) but slopes differed ((range 0.81-1.71); Figure 1. The Ref AVA assay has a sensitivity of 3.9 ng/mL and detects AVA at 0.5 mg/mL in the presence of VDZ levels of ≥50 mg/mL. All 4 vendor assays detected AVA but did not detect AVA in the presence of 15 mg/mL VDZ.

CONCLUSION:

Despite good specificity and selectivity, there are differences between the Ref assays Takeda has used in its clinical trials and commercial assays. This should be acknowledged when interpreting assays results with vedolizumab commercial assays.
676 Infliximab Trough Level or Combination Immunomodulator Therapy: Which Correlates Best With Mucosal Healing in IBD?
Authors: Al-Bawardy Badr , Jenkins Sarah , Snyder Melissa , Loftus Edward V. , Willrich Maria
Published: October 2019

INTRODUCTION:

Combination immunomodulator (IMM) with infliximab (IFX) has been shown to be superior to IFX monotherapy therapy in the management of inflammatory bowel disease (IBD). It is unclear if this is related to IMM solely or higher IFX trough level (IFX-TL). The aims of this study are to examine the correlation of IFX-TL with clinical outcomes of IBD patients and to evaluate whether IFX-TL or combination IMM therapy correlate best with mucosal healing (MH).

METHODS:

This is a retrospective study of consecutive IFX treated IBD patients undergoing drug monitoring with liquid chromatography-tandem mass spectrometry (LC-MS/MS). IMM included either thiopurines or methotrexate. Primary analyses included: comparing IFX-TL with clinical remission, MH (absence of mucosal ulcers in Crohn's disease (CD) and Mayo endoscopic score ≤1 for ulcerative colitis (UC)) and normal c-reactive protein (CRP ≤8 mg/L). Secondary analyses included determining an IFX-TL cut off to achieve MH and evaluating the predictors of MH (IMM vs. IFX-TL).

RESULTS:

A total of 151 patients were included (67% CD, 24% UC, 6% indeterminate colitis, 3% pouchitis) (Table 1). The median IFX-TL was 7 mcg/mL (IQR: 1.3, 19.4). The distribution of IFX-TL was not significantly different between patients in clinical remission, response and no response (median: 5.7 vs. 8.4 vs. 2.3 mcg/mL, respectively; P = 0.46). The median IFX-TL was significantly higher in patients who had a normal CRP (11.1 vs. 1.4 mcg/mL; P < 0.001) and in those who achieved MH (13.1 mcg/mL vs. 3.9 mcg/mL; P = 0.01). An IFX-TL ≥7.5 mcg/mL predicted MH with a sensitivity of 67% and specificity of 64% (AUC = 0.67; Figure 1). Combination therapy was associated with higher IFX-TL (median: 15.8 vs. 4.6 mcg/mL; P < 0.001). In a multivariable model to predict MH based on IFX-TL (continuously), combination therapy (yes vs no), dosing frequency (≥8 vs <8 weeks), and albumin (<3.5 vs ≥3.5), higher IFX-TL was associated with higher likelihood of MH (OR for 5-mcg/mL increase: 1.18, 95% CI 1.01-1.39; P = 0.04). In this model, IMM combination was not significant (OR: 0.79, P = 0.66), neither was dosing frequency (OR: 1.44, P = 0.48). Low albumin showed lower likelihood of MH, but this was not statistically significant (OR 0.14, 95% CI: 0.02-1.16, P = 0.07).

CONCLUSION:

IFX-TL was associated with normal CRP and MH but not clinical remission in this cohort of IBD patients. IFX-TL and not combination IMM therapy was independently associated with MH.
677 Outcomes of Infliximab Treated IBD Patients Undergoing Simultaneous Therapeutic Drug Monitoring With Two Different Assays
Authors: Al-Bawardy Badr , Jenkins Sarah , Snyder Melissa , Loftus Edward V. , Willrich Maria
Published: October 2019

INTRODUCTION:

There are multiple assays for infliximab (IFX) trough level (IFX-TL) and antibody (ATI) measurement. The aims of this study are to examine the correlation and outcomes of IFX-TL and ATI measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and electrochemiluminescence (ECLIA) in inflammatory bowel disease (IBD) patients.

METHODS:

This was a prospective study of IFX-treated IBD patients undergoing drug monitoring with an ECLIA panel (Esoterix Laboratories). Residual serum samples were used to simultaneously quantify IFX-TL via LC-MS/MS and ATI via an in-house ECLIA (iECLIA) (Mayo Clinic). Both LC-MS/MS and iECLIA have been previously validated. Primary outcomes: IFX-TL and ATI comparison between the two assays. Secondary outcomes: association of IFX-TL and ATI with clinical remission, mucosal healing (MH) (absence of ulcers in Crohn's disease and Mayo endoscopic score ≤1 for ulcerative colitis) and normal serum C-reactive protein (CRP ≤8 mg/L).

RESULTS:

A total of 151 patients were included (median age 32 years (12-84), 45.7% female) (Table 1). Median IFX-TL was 7 mcg/mL (IQR: 1.3, 19.4) and 6 mcg/mL (IQR: 0.9, 20) via LC-MS/MS and ECLIA, respectively (Spearman correlation coefficient r = 0.975). Median IFX-TL via LC-MS/MS was not significantly different between patients in clinical remission, response and no response (5.7 vs. 8.4 vs. 2.3 mcg/mL, respectively; P = 0.46), but significantly higher in patients who had a normal CRP (11.1 vs. 1.4 mcg/mL; P < 0.001) and in those who achieved MH (13.1 mcg/mL vs. 3.9 mcg/mL; P = 0.01). ATI was detected in 13/142 (9.2%) via iECLIA and 39/151 (25.8%) via ECLIA. The frequency of ATI detection via iECLIA was lower in patients in clinical remission or response than no response (7.3% vs. 9.3% vs. 15.4%; P = 0.68). On the contrary, the frequency of ATI detection via ECLIA was higher in patients with clinical remission (35.7%) than response (18.7%) and comparable to patients who had no clinical response (40%) (P = 0.05) (Table 2). The frequency of ATI was not significantly different between patients who did and did not achieve MH or had normal CRP using both assays (Table 2).

CONCLUSION:

IFX-TL was comparable between LC-MS/MS and ECLIA assays. IFX-TL correlated with MH and normal CRP but not clinical remission. Frequency of ATI detection was not significantly associated with outcomes via both methods. ATI detected via iECLIA showed a trend towards correlation with clinical outcomes compared to ECLIA.
678 Efficacy of Upadacitinib as an Induction Therapy in Severe and Refractory Ulcerative Colitis: Sub-Group Analysis of the Phase 2b Study U-ACHIEVE
Authors: D'Haens Geert R. , Lindsay James O. , Loftus Edward V. , Zhou Wen , Cataldi Fabio , Xie Wangang , Pugatch David , Panaccione Remo
Published: October 2019

INTRODUCTION:

An unmet need exists to find effective therapy in more severe ulcerative colitis (UC) patients, especially those who have failed multiple therapies. The efficacy and safety of upadacitinib, a selective Janus Kinase 1 inhibitor, has been assessed in an 8-week double-blind, placebo-controlled, dose-ranging, phase 2b induction study in adult patients with moderately-to-severely active UC (U-ACHIEVE).1,2

METHODS:

In U-ACHIEVE, adult patients with moderately-to-severely active UC as determined by the Adapted Mayo Score (5-9 points and centrally-read endoscopy subscore 2-3) were randomized to receive extended-release upadacitinib 7.5, 15, 30, 45 mg once daily (QD) or placebo for 8 weeks. In the current sub-analysis, the efficacy of upadacitinib in more severe and/or more refractory patient populations was assessed. Patients who at baseline had failed ≥2 prior biologic agents, had pancolitis, and/or an Adapted Mayo score >7, were included. Pairwise comparisons between upadacitinib doses and placebo for the primary endpoint, clinical remission per Adapted Mayo Score at Week 8 (defined as stool frequency subscore ≤1, rectal bleeding subscore = 0, and endoscopic subscore ≤1) and secondary endpoints were conducted using the Fisher's Exact test and no multiplicity adjustments were applied. Non-responder imputation was utilized for missing values.

RESULTS:

At baseline, 142 (56.8% of the total study population) patients had failed ≥2 prior biologics, 135 (54.0%) patients had pancolitis, and 90 (36.0%) patients had an Adapted Mayo score >7. The proportions of patients achieving endoscopic improvement, clinical response per Adapted Mayo score, and clinical response per Partial Mayo score were significantly higher (nominal P-value < 0.05) with upadacitinib doses ≥30 mg QD versus the placebo group in patients who failed ≥2 biologics or had pancolitis at baseline (Table 1). Trends of higher proportions of patients achieving clinical remission per Adapted Mayo score, endoscopic improvement, clinical response per Adapted Mayo score, and clinical response per Partial Mayo score were observed with all upadacitinib groups versus placebo in all the sub-analyses.

CONCLUSION:

In this dose-ranging induction study, upadacitinib demonstrated greater efficacy compared to placebo with dose response in the more severe and refractory population; significantly greater efficacy was demonstrated with upadacitinib at doses ≥30 mg QD for most of the endpoints evaluated.
681 Baseline Characteristics of a Retrospective Cohort of Patients With Inflammatory Bowel Disease Initiating Vedolizumab Therapy: Data From a Patient-Focused Application (HealthPROMISE)
Authors: Cohen Benjamin L. , Chang Helena , Rogers Jason , Garg Shashank , Lawrence Debra , Fasihuddin Farah , Lissoos Trevor , Atreja Ashish
Published: October 2019

INTRODUCTION:

Ulcerative colitis (UC) and Crohn's disease (CD) are chronic disorders of the gastrointestinal tract associated with high morbidity and decreased quality of life (QOL). The objectives were to assess health resource use, inflammatory biomarkers, and QOL in a cohort of inflammatory bowel disease (IBD) patients initiating vedolizumab therapy by analyzing existing data from both electronic health records (EHR) and the patient-focused application HealthPROMISE.

METHODS:

A retrospective cohort of adult IBD patients initiating vedolizumab between June 2014 and April 2019 at the Mount Sinai Medical Center (MSMC) infusion center was analyzed. Baseline data from the 1-year period prior to first vedolizumab infusion are reported. Health resource use and inflammatory biomarkers were extracted from EHR. IBD symptoms and QOL (Short Inflammatory Bowel Disease Questionnaire [SIBDQ]) were collected from the HealthPROMISE application. Descriptive analyses were conducted using SAS® v9.4.

RESULTS:

A total of 877 patients (502 with UC and 368 with CD, with a mean age of 39.6 years [SD = 16.2] and 51.8% female) was included. At baseline, mean levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and hemoglobin were as follows: 22.4 mg/L (SD = 54.0), 27.3 mm/h (SD = 21.5), 12.4 g/dL (SD = 1.7), respectively. Baseline SIBDQ scores and IBD symptom scores were 34.2 (SD = 13.0) and 4.8 (SD = 2.7), respectively. The proportion of patients with IBD-related hospitalizations, office visits, emergency room (ER) visits, procedures (surgical and nonsurgical), and medication use prior to initiating vedolizumab therapy are presented in Table 1.

CONCLUSION:

Baseline data collected from the HealthPROMISE application are limited; however, the scores reported are consistent with larger cohorts, suggesting that the HealthPROMISE application may be used to track QOL and patient-reported outcomes in IBD patients.