bluuebunny/crossref_metadata_2025 huggingface dataset:
734 Colonic Biopsy Pyroptosis Predicts Clinical Response to Vedolizumab in Crohn's Disease
Authors: Lavender Charles A. , Osterman Mark T. , Gordon Ilyssa O. , Davis Elisabeth M. , Ciorba Matthew A. , Glover Sarah C. , Abraham Bincy , Yee Eric U. , Allard Felicia D. , Young Grace , Shen Bo , Khan Freeha , Claggett Brian , Guo Xueyan , Stappenbeck Thaddeus S. , Liu Julia J.
Published: October 2019

INTRODUCTION:

Loss of intestinal barrier integrity plays a crucial role in the pathogenesis of inflammatory bowel disease (IBD). Pyroptosis, an innate immune-mediated form of inflammatory cell death of intestinal epithelial cells (IECs) that can be quantified, is a potential cause of mucosal barrier dysfunction in IBD. We have recently shown that ileal IEC pyroptosis level was predictive of clinical response to vedolizumab in Crohn's disease (CD) patients. Ileocecal valve disease and strictures can make it difficult to obtain ileal biopsies in some CD patients. Correlation of pyroptosis levels between ileal and colon biopsies is unknown. Our aims were to determine the predictive value of pre-treatment colonic biopsy IEC pyroptosis for clinical response to vedolizumab in CD patients and to assess the correlation between colonic and ileal biopsy pyroptosis levels.

METHODS:

CD patients from 5 IBD centers with pre-treatment ileal and colonic biopsies obtained were enrolled. The endpoint of clinical response, defined as reduction in Harvey-Bradshaw Index of ≥5 points, was assessed ≥6 months post-treatment. Biopsies were sectioned and stained, and samples with a minimum of 10 intact crypts were analyzed by a blinded pathologist. Pyroptosis was quantified as the number of counted cells staining for activated caspase-1 normalized per 1000 cells. The primary outcome was comparison of clinical response rates to vedolizumab stratified by pre-treatment colonic IEC pyroptosis using Fischer's exact test. The secondary outcome was correlation between ileal and colonic samples using Spearman's correlation.

RESULTS:

Fifty-five CD patients were enrolled. Non-responder and responder groups differed significantly only with respect to prior anti-TNF exposure and immunomodulator use (Table 1). The overall clinical response to vedolizumab was 62% (34/55). Using a threshold level of 30 positive cells/1000 IECs, the clinical response rate in patients with pyroptosis below this was significantly higher compared to those above the threshold: 69% (31/45) vs. 30% (3/10), OR 5.2 (1.2, 23.0), P = 0.031. The correlation between ileal and colon biopsy pyroptosis levels was poor (rho = 0.08, P = 0.56).

CONCLUSION:

Pre-treatment colon pyroptosis level was predictive of clinical response to vedolizumab therapy in CD patients, independent of ileal biopsy pyroptosis levels.
735 Crohn's Disease Patients Who Do Not Qualify for Clinical Trials Have Similar Clinical and Endoscopic Response Rates to Ustekinumab to Those Who Qualify for Clinical Trials
Authors: Cohen Erica R. , Syal Gaurav , Ha Christina
Published: October 2019

INTRODUCTION:

The UNITI clinical trial demonstrated ustekinumab (UST) safety and efficacy for moderate to severe Crohn's disease (CD) patients. However, exclusion criteria preclude enrollment of complex patients impacting external validity of the findings. The aim of this study was to evaluate UST response in active CD patients who would not have qualified for the randomized controlled trials (RCTs).

METHODS:

A retrospective cohort study of UST-treated CD patients who would not qualify (DNQ) and who would qualify (Q) for RCTs from 2016 to 2018 was performed. Inclusion criteria included symptomatic luminal CD activity (defined as abdominal pain and stool frequency), induction with UST infusion at CD dosing and ≥1 clinic visit post-induction. Criteria for DNQ patients were extracted from the published UNITI study protocol. The primary outcome of interest was week 8 clinical response rates (>50% improvement in abdominal pain and stool frequency from baseline) between Q vs DNQ groups. Secondary outcomes were endoscopic response, corticosteroid free clinical remission, dose escalation and adverse events between the two groups.

RESULTS:

201 patients (Q = 111; DNQ = 90) with a median 6 months follow up (IQR 4-9 months) were included. The DNQ cohort had lower hemoglobin levels, more active perianal disease, upper tract disease, ileocolonic disease, and prior surgeries (Table 1). Week 8 clinical response rates were similar between Q and DNQ (64.0% vs 60.0%; P = 0.56). Clinical response, remission and steroid-free remission rates during maintenance were also similar between the two groups (Table 2). However, more patients in the DNQ group required dose escalation (64.4%) compared to the Q group (46.8%), P = 0.01, especially after induction dosing. Endoscopic response rates were similar between Q and DNQ groups, with complete mucosal healing achieved in 13.2% vs 13.6% of Q and DNQ patients (P = 0.94) (Table 2).

CONCLUSION:

These findings suggest that ustekinumab is equally efficacious for complex CD patients who would not have qualified for RCTs. Adverse events were infrequent for all UST treated patients. The majority of DNQ patients required dose escalation during their treatment course, suggesting more intensive therapy may be warranted for this patient subgroup. Further studies are needed to determine durable clinical and endoscopic response from dose escalation in this complex CD group.
736 Vedolizumab: Peri-Operative Infection Rates in Patients With IBD
Authors: Mehta Ripple , Abidian Mohamed Modar , Bayasi Mohammed , Mattar Mark C.
Published: October 2019

INTRODUCTION:

Vedolizumab (VDZ), a humanized monoclonal antibody, binds to the alpha4beta7 integrin and blocks the interaction of mucosal cell adhesion molecule-1 thus inhibiting the migration of memory T-lymphocytes into inflamed GI parenchymal tissue. This interaction is a hallmark of Ulcerative colitis (UC) and Crohn's disease (CD). It has been used as an alternative therapy to anti-tumor necrosis factor (anti-TNF) agents for Induction and maintenance in patients with moderate to severe inflammatory bowel diseases (IBD). Due to its immunosuppressive effects, VDZ maybe associated with increased risks of infections. Therefore, it is imperative to study the infection rate in this population, particularly during the perioperative period. Our objective is to identify perioperative infection rates in patients with Inflammatory Bowel Disease (IBD).

METHODS:

A retrospective multi-center case-control study was conducted. Patients with IBD in the period from May 2014 to Dec 2017 were included. Two groups were studied (Pt with IBD and on VDZ, Pt with IBD and not on VDZ). The perioperative period was identified as up to 30 days post-index surgery. ICD-10 codes for intra-abdominal surgeries and infections were used to identify population. Patients developing only new infections were included. Data were classified into two cohorts for the purpose of comparison: Cohort 1 included all-infections and Cohort 2 included only intra-abdominal infection. Different models of logistic regression data analysis were performed.

RESULTS:

Logistic regression data analysis was performed including simple, multiple and mixed model for both cohorts. The mixed model included multiple encounters per person, age, gender, ethnicity, and race. Results of Cohort 1 showed odds ratio (OR) = 1.332 (CI 0.599-2.965, P = 0.4821). Results of Cohort 2: OR = 1.286 (CI 0.426-3.882, P = 0.6551). These findings indicated that there was no statistical significance between increased rates of peri-operative infection rates and VDZ use.

CONCLUSION:

Our findings suggested that VDZ is relatively safe to use during the perioperative period. There are a few small studies indicating similar results, however, a unique aspect of our study was to include broad-spectrum infection types (sepsis from any source such as pneumonia, UTI) and not only intra-abdominal or surgery-related infections. We do recommend further investigations with more controlled study and larger population coverage to further solidify our findings.
740 Prevalence of Anorectal Fistula's in Crohn's Disease: A National, Population-Based Study
Authors: Sheriff Mohammed Z. , Tunio Nahel A. , Mansoor Emad , Dave Maneesh
Published: October 2019

INTRODUCTION:

Perianal fistulizing disease is associated with significant morbidity and impairment in the quality of life in patients with Crohn's disease (CD). However, there is limited national level data on the prevalence of anorectal fistulas (AF) in CD. Similarly, there is a paucity of data on the prevalence of CD in patients with an initial presentation of an AF.

METHODS:

The aim of this study was to investigate the prevalence of AF in patients with CD, and to estimate the prevalence of CD in patients with an initial presentation for AF in a large, national database. Data was collected from a commercial database (Explorys Inc, Cleveland, OH) that provided electronic health records from 27 major integrated US healthcare systems from 1999 to June 2019. In this dataset, we identified all CD and AF based on Systemized Nomenclature of Medicine - Clinical Terms “Crohn's disease” and “Anorectal fistula.” We conducted searches with CD as the index event prior to the development of AF, and searches with AF as the index event prior to CD to identify the temporal relationship between CD and AF. We determined the prevalence of the second diagnosis at 30 days, 3 months, 6 months, 1 year, 3 years, and 5 years after the index event.

RESULTS:

Of the 63,036,150 individuals in the database, we identified 187, 070 patients with CD. Of these, 7,160 patients had a had a diagnosis of an AF after the diagnosis of CD, with an overall prevalence of 3.27%. The prevalence rate of AF in Caucasians, African Americans and Asians with CD was 3.79%, 5.08%, and 2.92% respectively. The prevalence of AF in CD varies with age (Figure 1) and the highest prevalence of AF was in the 35-49 year age groups. The majority (96%) of anorectal fistulas were identified within the first 30 days of CD diagnosis. Among the 63,036,150 individuals in the database, we identified 45,060 patients with anorectal fistulas. In this cohort, the prevalence of CD was 15.9%. The majority of cases of CD were diagnosed within 30 days of diagnosis of AF (6,630 out of 7,160, or 93% of CD cases). The overall prevalence ratio of CD in those with AF compared to those without AF was 55.6 [95% CI 54.4 to 56.9, P < 0.0001].

CONCLUSION:

In this large, cross sectional population database study, we determined that nearly 3.3% of CD patients have perianal fistula. Furthermore, 16% of all perianal fistulas are associated with a diagnosis of CD. Therefore, it is reasonable to screen all patients who are diagnosed with anorectal fistulas for CD.
744 The Impact of Ulcerative Colitis on Quality of Life and Productivity Across Europe: A Burden of Illness Study
Authors: Limdi Jimmy K. , Rose Alison , Noone Declan , Lobo Alan J. , Terry Helen , Hayee Bu , Burisch Johan , Peyrin-Biroulet Laurent , Fiorino Gionata , Avedano Luisa , Tucknott Seb , Sturm Andreas , Finnegan Alan , Evans Jonathan
Published: October 2019

INTRODUCTION:

The Living with Ulcerative Colitis: Identifying the socioeconomic burden in Europe (LUCID) study was a descriptive, retrospective, cross-sectional, European (France, Germany, Italy, Spain, United Kingdom, Denmark, Norway, Poland, Romania and Turkey), multi-site bottom-up Burden of Illness research study carried out by HCD Economics and the University of Chester in partnership with Crohn's and Colitis UK.

METHODS:

The aim of this study was to explore the impact of UC on patients' HRQoL (health-related quality of life) and productivity. Patients were recruited through Gastroenterologists (surveyed between Aug 2018-Feb 2019) and split into two population cohorts; Arm 1: Patients with moderate or severe UC status at initiation of documentation period (12 months prior the index date) and Arm 2: Patients with moderate or severe UC that achieved mild UC or remission at initiation of documentation period. Each patient was invited to complete a public patient involvement and engagement (PPIE) form. The PPIE included patient reported outcome measures (PROMs) to capture intangible costs using the Work productivity and impairment (WPAI) questionnaire, and HRQoL using the EQ5D.

RESULTS:

1,658 patients completed the PPIE form. Of these patients, 9 patients did not have their UC status recorded so could not be assigned to an arm. Out of these patients, 1,001 patients (60.7%) were categorised into arm 1 with 648 patients (39.3%) categorised into arm 2. 994 patients from arm 1 and 638 patients from arm 2 completed the EQ5D with a mean score of 0.81 (0.17 SD) and 0.86 (0.16 SD) respectively. The mean WPAI scores for arm 1 (n = 602) were 0.11 (0.25 SD) for work time missed (absenteeism), 0.24 (0.21 SD) for impairment (presenteeism), 0.28 (0.24 SD) for work impairment and 0.27 (0.24 SD) for activity impairment. The mean WPAI scores for arm 2 (n = 368) were 0.01 (0.19 SD) for work time missed (absenteeism), 0.24 (0.18 SD) for impairment (presenteeism), 0.2 (0.21 SD) for work impairment and 0.18 (0.2 SD) for activity impairment.

CONCLUSION:

Our preliminary results show that UC has implications on HRQoL and work productivity for all patients with UC, ranging from those in remission or mild disease to those with moderate or severe UC, underpinning the need for more holistic and inclusive definitions of care and disease control. Further analysis, to understand the impact of ulcerative colitis on patients, is ongoing to address this important and unmet need.
745 Developing Precision Medicine in IBD: Peripheral Blood Eosinophilia Identifies Individuals With Worse Outcomes Following Initiation of Anti-TNF Biologic Agents
Authors: Bettner Weston , Althouse Andrew , Rivers Claudia Ramos , Schwartz Marc , Proksell Siobhan , Johnston Elyse , Barrie Arthur , Al Hashash Jana , Harrison Janet , Babichenko Dmitriy , Tang Gong , Koutroubakis Ioannis , Binion David
Published: October 2019

INTRODUCTION:

Peripheral blood eosinophilia (PBE) has been recognized as a biomarker, identifying a subgroup of inflammatory bowel disease (IBD) patients with worse clinical outcomes. With more severe disease, anti-TNF therapy is often employed, with varied rates of success. The aim of this study was to determine whether the presence of pre-treatment PBE identifies IBD patients at risk for diminished anti-TNF treatment response.

METHODS:

We performed a registry analysis of IBD patients starting anti-TNF therapy who were enrolled in a consented, prospective, natural history IBD cohort at a tertiary center. Metadata was collected in the 2 years preceding and 2 years following anti-TNF initiation. The presence of PBE before and after anti-TNF initiation was recorded and treatment response was assessed for those with/without PBE using disease activity scores [Harvey Bradshaw Index (HBI) and Ulcerative Colitis Activity Index (UCAI)], quality of life measures [Short Inflammatory Bowel Disease Questionnaire (SIBDQ)], inflammatory markers (ESR, CRP), steroid use (prednisone or methylprednisolone), IBD-related hospitalizations, and IBD-related surgeries. Outcomes were assessed via linear mixed-effects and Cox proportional-hazards models for Crohn's disease (CD) and ulcerative colitis (UC).

RESULTS:

A total of 580 IBD patients (CD 430, UC 150) were included with 111 (19%) demonstrating pre-treatment PBE (CD 66, UC 45). Table 1 summarizes demographic and clinical data. Following anti-TNF therapy, CD patients with pre-treatment PBE were more likely to have an IBD-related hospitalization [adjusted hazard ratio (AHR) 1.88, 95% CI 1.22-2.90, P = 0.004] and require anal fistula repair (AHR 3.88, 95% CI 1.09-13.8, P = 0.04) than CD patients without PBE. UC patients with pre-treatment PBE were more likely to have an elevated CRP following anti-TNF therapy (OR 2.77, 95% CI 1.50-5.10, P = 0.001) with a non-significant trend towards increased IBD-related admissions and surgeries. CD patients with pre-treatment PBE were less likely to require steroids following anti-TNF therapy than CD patients without PBE (AHR 0.40, 95% CI 0.18-0.86, P = 0.019). There was no significant difference in HBI, UCAI, or SIBDQ scores in patients with/without PBE undergoing anti-TNF therapy.

CONCLUSION:

Pre-treatment PBE identifies IBD patients at risk for worse outcomes following anti-TNF therapy, particularly in CD. Further studies are warranted to determine if alternate mechanism of action biologics will function optimally in the PBE IBD population.
748 Ustekinumab Improved Work Productivity in Patients With Moderate to Severe Ulcerative Colitis: Results From the Phase 3 UNIFI Induction and Maintenance Studies
Authors: Han Chenglong , Naessens Dominik , Zhang Hongyan , Johanns Jewel , Marano Colleen , Sands Bruce E.
Published: October 2019

INTRODUCTION:

We evaluated the effect of ustekinumab (UST) on work productivity and daily activity in patients with moderate-severe active ulcerative colitis (UC) in the UNIFI induction and maintenance studies.

METHODS:

In the induction study, patients were randomized to a single intravenous (IV) dose of placebo (PBO, n = 319), UST 130 mg (n = 320), or UST ∼6 mg/kg (n = 322). Patients who were in clinical response 8 wks after receiving UST IV induction were eligible for the maintenance study and randomized to subcutaneous (SC) PBO (n = 175), UST 90 mg q12w (n = 172), or UST 90 mg q8w (n = 176). Work productivity was assessed using the Work Productivity and Activity Impairment Questionnaire (WPAI), a validated tool that assesses work time missed (absenteeism), reduced job effectiveness (presenteeism), overall work impairment, and daily activity impairment due to health over the previous week. The impact of UC on overall daily productivity at home, school, and work was assessed using a visual analog scale (VAS, 0 to 10, 0 = no impact at all, 10 = impacts very much).

RESULTS:

At induction baseline, patients had a mean percent work time missed ranging from 17.7% to 19.3%, impairment while working from 39.1% to 45.3%, overall work impairment from 43.7% to 49.1%, and activity impairment from 51.8% to 52.8%. At Wk 8, patients who received UST IV had significantly greater improvement in WPAI domains and daily productivity VAS compared with PBO (Table 1). In the maintenance study, UST-treated patients generally maintained or numerically improved WPAI scores, while scores for patients in the PBO group worsened. The mean changes from baseline to Wk 44 in work time missed was 4.7% in the SC PBO group, -2.0% (P = 0.133) in the SC UST 90-mg-q12w group, and 2.1% (P = 0.172) in the SC UST 90-mg-q8w group, impairment while working was 7.4%, −1.6 (P = 0.017), and −6.4% (P < 0.001), respectively; overall work impairment was 7.7%, −2.2% (P = 0.013), and −6.1% (P < 0.001), respectively; and activity impairment was 9.3%, 0.8% (P = 0.002), and −4.2% (P < 0.001), respectively. Mean changes from baseline to Wk 44 in daily productivity VAS scores were 1.0, −0.2 (P < 0.001), and −0.5 (P < 0.001), respectively.

CONCLUSION:

Patients who received UST IV induction reported significantly greater improvement in work productivity and daily activity compared with PBO. In patients who responded to UST IV induction, those who received UST SC maintenance through Wk 44 sustained or improved the levels of work productivity and activity that were achieved during induction.
749 Medication Use and Comorbidities Among Elderly as Compared to Younger Patients With Inflammatory Bowel Disease in the TARGET-IBD Cohort
Authors: Barnes Edward L. , Hanson John , Regueiro Miguel , Saha Sumona , Sands Bruce E. , Rubin David T. , Dubinsky Marla C. , Siegel Corey A. , Gazis Derek R. , Crawford Julia M. , Long Millie D.
Published: October 2019

INTRODUCTION:

As compared to younger patients, much less is known regarding inflammatory bowel disease (IBD)-related medications in elderly (>65 years) patients. This analysis uses a large cohort of patients with IBD to describe the distribution of patient characteristics and patterns of medication use.

METHODS:

TARGET-IBD is a longitudinal cohort of patients with IBD receiving usual care at community and academic practices in the US. Patients with IBD enrolled between July 2017 and May 2019 were included in this analysis. The prevalence of medication use by drug class at the time of enrollment among patients with both ulcerative colitis (UC) and Crohn's disease (CD) was estimated. Age was stratified into the following categories: >30, 30-49, 50-65 and >65 years. Proportions and means of patient characteristics were compared using tests of association. The odds of biologic use at enrollment was modeled as was the 95% CI by patient characteristics using logistics regression.

RESULTS:

681 patients with UC and 979 patients with CD were included in the analysis. At enrollment, mesalamine was the most common medication used among patients with CD > 65 years (34%) and among patients with UC across all age categories (58%-77%, Table 1). Use of mesalamine generally increased with advancing age. Patients with CD > 65 years were more than twice as likely to be users of mesalamine at enrollment than patients <30 years (P < 0.0001). Among patients with either disease type, anti-tumor necrosis factor alpha (anti-TNF) use decreased in patients >65 years compared to patients <30 years. Thiopurine use did not vary across age categories. Among patients >65 at enrollment, use of a 5-ASA derivative, anti-TNF, steroid or thiopurine did not differ by established and newly diagnosed patients. There was no association between age, type of IBD, insurance, gender, race or cardiovascular disease and the odds of biologic use in patients >65 years (Figure 1).

CONCLUSION:

Elderly patients with IBD, whether those with new diagnoses or individuals with longstanding disease make up a substantial portion of the IBD population. Given that elderly patients demonstrate significant differences in medication use patterns compared to younger patients with IBD, studies of efficacy and adverse events specific to this population are warranted.
752 Should Gastroenterologists Screen Immunosuppressed IBD Patients for HIV?
Authors: Naik Katrina , Borum Marie , Khan Ali , Boortalary Tina , Imasuen Esosa
Published: October 2019

INTRODUCTION:

HIV screening is recommended in all patients aged 15-75 years once in their lifetime and more frequently if at higher risk, including those taking immunosuppressive therapy. Gastroenterologists are uniquely positioned to improve screening rates since they prescribe immunosuppressive therapy to inflammatory bowel disease (IBD) patients. This study evaluated the frequency of HIV screening among IBD patients on immunosuppressive therapy at a university medical center.

METHODS:

A retrospective chart review of all IBD patients at an urban academic medical center seen during a 5-year period was performed. Patient gender, age, race/ethnicity, disease type, medication regimen, HIV screening and ordering physician specialty were obtained. Exclusion criteria were a previous HIV diagnosis or not receiving immunosuppressive treatment. A confidential database was created using Microsoft Excel with statistical analysis set at <0.05. This study was approved by IRB.

RESULTS:

Medical records of 392 IBD patients were reviewed. Of the 226 patients on immunosuppressant therapy, 97 (42.9%) males and 129 (57.1%) females were a mean age of 43.3 years. 58 (25.7%) had Crohn's Disease, 161 (71.2%) had ulcerative colitis and 8 (3.5%) had indeterminate colitis. 93 (41.2%) were screened for HIV. Three (0.004%) were HIV positive. African Americans were screened significantly more than non-African Americans (61.5%, 31.3%; P = 0.0001). There were no significant differences in HIV screening by gender (37.1% M, 44.2% F; P = 0.339); age (40.3% < 45 years, 42.4% ≥45 years; P = 0.784); or IBD type (51.7% CD, 37.9% UC; P = 0.0870). Primary care doctors screened for significantly more (51.6%) than obstetricians/gynecologists (22.6%; P = 0.0001) or other specialty physicians (9.7%; P = 0.0001) (Figure 1).

CONCLUSION:

Chronic colonic inflammation may contribute to CD4 lymphocyte depletion and negatively impact HIV outcome. While there are few HIV-infected patients in this study, HIV vulnerability may vary in other immunosuppressed populations. While this study is limited by size, single-institution design and focus on immunosuppressed IBD patients, it offers a foundation for future research and preventive health care efforts. It is important that all at-risk populations be screened for HIV with a focus on eliminating racial disparity. Gastroenterologists have the potential to significantly improve HIV testing for at-risk populations. Increased efforts are needed to heighten all physicians' awareness of HIV testing recommendations.
764 Long-Term Efficacy and Safety of Etrasimod for Ulcerative Colitis: Results From the Open-Label Extension of the OASIS Study
Authors: Chiorean Michael , Vermeire Séverine , Panés Julian , Peyrin-Biroulet Laurent , Zhang Jinkun , Sands Bruce E. , Lazin Krisztina , Cabell Chris H. , Naik Snehal U. , Klassen Preston , Sandborn William J.
Published: October 2019

INTRODUCTION:

Etrasimod, a once-daily, oral, selective, sphingosine-1-phosphate receptor modulator, was previously tested in the 12-week (wk) phase 2, randomized, placebo-controlled, double-blind (DB) OASIS study (NCT02447302) in adults with moderate–to–severe ulcerative colitis (UC). This open-label extension (OLE) study (NCT02536404) evaluated safety/efficacy of etrasimod for an additional 34 wk in OASIS completers.

METHODS:

All patients completing the DB study could enroll in the OLE and receive etrasimod 2 mg QD for a subsequent 34 wk. Efficacy was summarized in the modified intent-to-treat (mITT) population evaluable cohort, which included patients with required assessments who received etrasimod 2 mg throughout the OLE. The treat-through (TT) group received etrasimod 2 mg in both the DB and OLE studies. Endpoints were clinical remission (endoscopic score ≤1 [with absence of friability], rectal bleeding [RB] = 0, and stool frequency [SF] score ≤1 with ≥1 point decrease from DB baseline), clinical response (clinical remission or decrease in modified Mayo Clinic score [endoscopy findings, RB, or SF] of ≥2 points and ≥30% decrease from DB baseline, with either a RB decrease of ≥1 or RB score of ≤1), and endoscopic improvement (subscore ≤1). All statistics are descriptive. End of treatment (EOT) was the last observation for each patient.

RESULTS:

118 patients (84% of DB completers) entered the OLE; 112 patients received etrasimod 2 mg at any point in the OLE (safety population), of whom 105 received etrasimod 2 mg throughout the OLE (evaluable cohort), and 92 completed the OLE. At EOT, 70% of patients had a clinical response, increased from 40% at wk 12 (Table 1). Most patients with clinical response, clinical remission, or endoscopic improvement at wk 12 maintained that status at EOT (Table 2). Median lymphocyte reduction from DB baseline was 44.6% at wk 12 with etrasimod 2 mg and 42.9% at EOT in the TT group. In the safety population, 60% experienced ≥1 TEAE (mostly mild or moderate) and 9% stopped study drug due to a TEAE. Of 14 serious TEAEs in 7 patients, only 1 was considered treatment-related (worsening UC). Effects on heart rate and atrioventricular (AV) conduction were minimal; no patients withdrew due to bradycardia or AV block.

CONCLUSION:

Etrasimod 2 mg showed sustained clinical response, clinical remission, and endoscopic improvement at the end of the OLE. Etrasimod had a favourable long-term safety profile, with most AEs of mild to moderate severity; no new safety findings were reported.
765 Low Skeletal Muscle Index Is an Independent Risk Factor for Inflammatory Bowel Disease Surgical Complications
Authors: Berger Matthew , Micic Dejan , Sakuraba Atsushi
Published: October 2019

INTRODUCTION:

Pre-operative assessment is necessary to determine if patients with inflammatory bowel disease (IBD) will benefit from nutrition support. The relationship between skeletal muscle area and the prognosis of patients who undergo surgery for IBD remains undetermined. This study aims to evaluate the skeletal muscle index (SMI) area as a predictive marker for surgical outcomes in patients with IBD.

METHODS:

Data were collected retrospectively for consecutive surgeries for IBD complications between March 2014 and April 2016. The primary outcome of interest was infectious and non-infectious post-operative complications. The SMI was measured using the cross-sectional computed tomography images at the mid-L3 level using ImageJ. Sarcopenia was defined using previously validated SMI categories adjusted for sex and BMI. Data were analyzed using Wilcoxon rank-sum test for continuous variables and Fischer's exact test for categorical variables. Multivariate logistic regression was performed to identify independent factors predictive of postoperative complications.

RESULTS:

439 patients were included in the final analysis. 92 (20.1%) patient had cross-sectional imaging available for sarcopenia evaluation. 178 (40.5%) experienced post-operative complications. In univariate analysis, Crohn's disease, SMI, Nutrition Risk Index, albumin, CRP, and BUN were associated with increased risk of 30-day postoperative complications (Table 1). In multivariate analysis, only sarcopenia as defined by Martin et al. (OR = 5.6; CI: 1.7-18.3) was significantly predictive of postoperative complications. In subgroup analysis, sarcopenia was found to be predictive of infectious postoperative complications (57.1% versus 22%, P = 0.001).

CONCLUSION:

Skeletal muscle index utilizing previously defined categorical variables is a readily available and significant independent risk factor for 30-day postoperative complications in IBD with a strong association with infectious complications. Further interventional studies are required to define our abilities to mitigate post-operative complications based on these findings.
766 Predictors and Trends in Hospitalized Patients With Inflammatory Bowel Disease and Colorectal Cancer That Develop Venous Thromboembolism: A Retrospective Review
Authors: Palacios Pedro , Attar Bashar M. , Mbachi Chimezie , Chukwujindu Ezekiel , Paintsil Isaac , Nwaichi Chineme , Vohra Ishaan , Majeed Muhammad , Wang Yuchen , Gandhi Seema
Published: October 2019

INTRODUCTION:

Inflammatory bowel disease (IBD) is an idiopathic inflammatory process affecting the gastrointestinal tract. Patients with IBD have been shown in several studies to be at higher risk of venous thromboembolism (VTE) and colorectal cancer (CRC) compared to the general population. IBD and CRC have different prothrombotic properties; it is unknown how the interaction of these prothrombotic properties in patients with both IBD and CRC predicts the development of VTE in hospitalized patients necessitating the current study.

METHODS:

The national inpatient sample (NIS) from 2005-2014 was queried for all patients with a co-diagnosis of IBD and CRC who were hospitalized with a diagnosis of VTE as one of the top three discharge diagnosis using ICD9 codes 4534.X, 4533.X, 4511.X, 4518.X, 4151.X, 4538.X and 4151.X. The main outcome was the predictors of VTE. While secondary outcomes were trend in prevalence, length of stay, total charge and in-patient mortality among patients with VTE. All analysis was done using STATAv14.

RESULTS:

7,585 adults with a co-diagnosis of IBD and CRC were included, among which 197 (2.5%) were coded to have VTE as one of their top three diagnoses. Multivariate logistic regression showed that black race patients (10.6% vs 5.2%; aOR 2.33 [1.40-3.89], P = 0.001), patients with metastasis (27.9% vs 16.7%; aOR 1.67 [1.17-2.40], P = 0.005) and with pulmonary circulation disorders (27.4% vs 1.2%) aOR 28.52 [18.8-43.1], P = < 0.001) had more odds of having VTE while patients with uncomplicated diabetes (8.1% vs 15.5%; aOR 0.47 [0.26-0.84], P = 0.012) had less odds of having VTE. Obesity and anemia were significantly associated with VTE in univariate logistic regression analysis but lost its significance on multivariate logistic regression analysis. VTE was also associated with more length of stay (8.41 vs 6.87 days, P = 0.005) and more total charges ($64,388 vs $50,874, P = 0.009). There was no significant trend in the prevalence of VTE neither was VTE associated with a higher odds of mortality.

CONCLUSION:

VTE was more common in patients with metastatic cancer and pulmonary circulation disorders compared to patients with localized disease while obesity and anemia lost significance after multivariate logistic regression analysis. Patients with IBD and CRC might have peculiar procoagulant properties different from patients with only IBD or CRC and might require tailored strategies to stratify these population into a different category so as to develop more directed VTE prophylaxis regimen.
769 Association Between Vitamin D Deficiency and Inflammatory Bowel Disease (IBD)
Authors: Baidoun Firas , Sarmini Muhammad Talal , Alkhadra Yasser , Khoudari George , Shen Bo
Published: October 2019

INTRODUCTION:

Inflammatory bowel disease (IBD) with its two major forms, ulcerative colitis (UC) and Crohn disease (CD), has an increasing incidence rate worldwide. Vitamin D deficiency is a common disorder and it has been more prevalent in the last twodecades. multiple studies have shown a link between vitamin Dlevel and IBD severity raising the question of vitamin Ddeficiency role as a risk factor for IBD. The goal of this study is to investigate the association between vitamin D deficiency and IBD using a large inpatient data base.

METHODS:

By using the data from the National Inpatient Sample (NIS) database between 2002 and 2014, we identified the patients with vitamin D deficiency and IBD diagnosis using the International Classification of Diseases 9th version codes (ICD-9). The control group was the patients without vitamin D deficiency using the ICD-9 codes. We did multivariate logistic regression analysis to calculate the association between vitamin Ddeficiency and IBD.

RESULTS:

The study had total 101,137,145 patients. The vitamin Ddeficiency group had 339,418 patients (0.34%). We noticed that patients with vitamin D deficiency were older with mean age (63 vs 48), had more African American patients (17% vs 14%) and more female patients (67% vs 58%) (P < 0.001 for all). The vitamin D deficiency group had more patients with obesity (16% vs 7%) and more tobacco use (11% vs 10%) (P < 0.001 for all) (Figure 1). Using univariate analysis, we found patients with vitamin Ddeficiency had higher rate of IBD compared with patients without vitamin D deficiency (Odds Ratio [OR], 2.539, 95% confidence interval [CI], 2.474-2.605, P < 0.001), then we used multivariate logistic regression analysis, and after adjusting for potential cofounding factors, patients with vitamin D deficiency had a statistically significant higher rate of IBD (Odds Ratio [OR], 2.35, 95% confidence interval [CI], 2.285-2.417, P < 0.001) compared with patients without vitamin D deficiency (Figure 2).

CONCLUSION:

Based on our study we found that patients with vitamin D deficiency have two times higher risk of having IBD compared to patients without vitamin D deficiency. This raise the importance of screening for vitamin D deficiency in IBD patients. Further studies are needed to assess the role of vitamin D supplement in IBD course and outcome.
778 Association Between Serum Albumin Levels and the Rate of Active Crohn's Disease in Patients Seen at a Tertiary Care IBD Center
Authors: Harris Patrick , Matin Tasnia , Zhang Nan , Talha Malik
Published: October 2019

INTRODUCTION:

Crohn's Disease (CD) is a chronic inflammatory condition, primarily of the gastrointestinal tract with an increasing incidence and prevalence worldwide. In clinical practice, gastroenterologists are often faced with challenges in evaluating disease activity, severity, and prognosis to guide appropriate management of CD. We studied the association between serum albumin level and the rate of active clinical disease in CD patients seen at a tertiary care Inflammatory Bowel Disease (IBD) referral center.

METHODS:

We designed a retrospective cohort study using adult patients (>18 years) with CD followed for at least one year at University of Alabama at Birmingham (UAB) IBD center by a single trained IBD specialist between 2014-2018. Serum albumin levels were divided into: low mean serum albumin (≤3.2 mg/dL) vs. appropriate mean serum albumin (>3.2 mg/dL). Clinical disease activity was measured using the Harvey-Bradshaw index (HBI). Active disease was defined as HBI score of 8 or higher. Poisson Regression Models (GPR) for Rate Data were used to estimate partially adjusted and fully adjusted incidence rate ratios (IRR) of active clinical disease among CD patients. We also examined IRRs for serum albumin level as a continuous variable.

RESULTS:

In this single IBD practice at UAB, 269 patients with CD had albumin drawn at initial visit and serially at each subsequent visit. Poisson regression model adjusted for age, gender, race, duration of disease, steroid use, smoking and Crohns location demonstrated that CD patients with a low mean serum albumin during clinical observation were approximately 1.5 times more likely to have active clinical disease during observation (IRR 1.49, 95% CI 1.04-2.15, P = 0.032) compared to those with a serum albumin level of >3.2 mg/dL. The adjusted model with serum albumin as a continuous variable demonstrated that with every unit (0.1 mg/dL) reduction in mean serum albumin, there was 30% higher likelihood of active Crohns in clinic (IRR 1.30, 95% CI 1.02-1.66, P = 0.037).

CONCLUSION:

Lower mean serum albumin during clinical observation is associated with a higher likelihood of active clinical disease among CD patients. Whether interventions designed to correct or increase serum albumin stores/levels in these patients would be beneficial remains to be examined.
779 Dietary Practices and Beliefs of British South Asian Patients With Inflammatory Bowel Disease: A Prospective Study From the United Kingdom
Authors: Crooks Benjamin J. , McLaughlin John , Limdi Jimmy K.
Published: October 2019

INTRODUCTION:

The increasing incidence of inflammatory bowel disease (IBD) in developing countries and immigrant populations appears to outpace that which genetic influences alone could instigate and implicates “westernisation” and diet in the aetiopathogenesis of IBD.
1
Limited data exist on the dietary practices of the migrant South Asian population with IBD. We aim to describe the dietary practices of British South Asian patients with IBD and the information resources which guide these beliefs.

METHODS:

A prospective, cross-sectional, questionnaire-based study is being conducted in the UK. Two-hundred South Asian patients with IBD will complete a questionnaire regarding demographics and dietary practices. Here we provide an interim analysis of the data collected from the first 27 patients.

RESULTS:

Mean patient age was 36.1 years (59% male). 56% had UC and 44% Crohn's. 62% identified themselves as Pakistani, 19% as Indian and 19% as Bangladeshi. 74% of patients were born in the UK to parents born outside of the UK, the remaining 26% were born outside of the UK. Mean disease duration was 10.2 years. 48% considered diet to be an initiating factor in their IBD, based on their own experience (100%) and internet resources (31%). 63% of patients felt that diet had triggered a relapse of their disease, the most commonly reported foods being spicy (65%), fatty foods (53%), milk products (35%) and red meat (35%). 81% of patients avoided certain foods in an attempt to prevent an IBD “flare.” Most frequently avoided foods were spicy foods (91%), fatty foods (86%), coffee and carbonated drinks (55%) and red meat (50%). Just over a third of patients reported being able to find specific dietary advice for IBD, most commonly on the internet. Around half of patients avoided eating the same meal as their family or eating out to prevent relapse of their IBD.

CONCLUSION:

Dietary restriction may be highly prevalent amongst the British South Asian community with IBD with a high proportion reporting diet as an initiating factor and trigger for IBD. Studies on immigrant populations may hold valuable clues for IBD pathogenesis or related symptoms. A larger dataset will be presented at conference proceedings.
780 Dietary Practices and Beliefs of Patients With Older Onset Inflammatory Bowel Disease: A Prospective Study From the United Kingdom
Authors: Crooks Benjamin J. , McLaughlin John , Limdi Jimmy K.
Published: October 2019

INTRODUCTION:

In an aging population, 25-35% of those with inflammatory bowel disease (IBD) are over 60 years old. A third of these are diagnosed with IBD at or over the age of 60, so-called “older-onset” IBD [1]. Despite epidemiological associations implicating diet in IBD aetiology, virtually no studies exist exploring perceptions and beliefs of patients with older-onset IBD.

METHODS:

A prospective, cross-sectional, questionnaire-based study is being conducted in the UK. Two-hundred patients with older-onset IBD will complete a questionnaire regarding demographics and dietary practices. Here we provide an interim analysis of the data collected from the first 29 patients.

RESULTS:

Mean patient age was 73.5 years, 55% were male, 93% Caucasian, 69% had ulcerative colitis and 31% had Crohn's disease. Mean disease duration was 6.2 years. 24% of patients felt diet was an initiating factor in their IBD and this was based on their own experience (86%) or advice from a gastroenterologist (57%) or dietician (43%) in the majority of cases. Just under a quarter of patients believed that diet could trigger a relapse of their disease with 43% of these identifying both milk products and raw fruit and vegetables as the most common causes. 60% of patients avoided certain foods to prevent relapse. The most commonly avoided foods were spicy (82%) and fatty foods (65%), carbonated drinks (53%), red meat (47%) and alcohol (41%). Over 50% reported being able to find specific advice regarding dietary recommendations in IBD, and three-quarters of these used the internet to obtain this advice. A fifth of patients avoided eating the same menu as their family at least some of the time to prevent relapse of their IBD and 30% of patients avoided eating out. 17% had tried a specific exclusionary diet to help manage their disease.

CONCLUSION:

Despite a low proportion implicating diet in the initiation of IBD or its relapse, a significant number continue to restrict their diet. This, along with co-existing frailty, comorbidities and polypharmacy, may put this group of patients at increased risk of nutritional deficiency and its associated complications, underpinning the need for understanding the dietary practices and perceptions in this vulnerable group. A larger dataset will be presented at conference proceedings.
783 Nonalcoholic Fatty Liver Disease in a South Asian Crohn's Disease Population: External Validation of the St. Louis Steatosis Index
Authors: Tirath Ankita , McHenry Scott , Ganesh Girish , Ciorba Matthew A. , Sharma Mithun , Banerjee Rupa , Deepak Parakkal
Published: October 2019

INTRODUCTION:

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease affecting one-quarter of the world population. NAFLD is also an extra-intestinal manifestation of Crohn's Disease (CD), where it is associated with higher morbidity and mortality. We aimed to (1) characterize risk factors for NAFLD in South Asian CD pts, and (2) externally validate a clinical prediction score for NAFLD in CD, the St. Louis Steatosis Index (SLSI).

METHODS:

We prospectively enrolled CD pts from 2/1/2019-5/31/2019 at the Asian Institute of Gastroenterology, a tertiary referral center for Inflammatory Bowel Disease (IBD) in India. Exclusion criteria included an alternative etiology of liver disease (e.g., chronic viral hepatitis). Controlled attenuation parameter (CAP) with transient elastography was measured using FibroScan® (Echosens, Waltham, MA) to quantitate hepatic steatosis and fibrosis. The outcome of NAFLD was defined as CAP ≥ 240 dB/m with the secondary outcome of hepatic fibrosis defined as ≥7 kPa. The SLSI operating characteristics were compared at re-calibrated low risk (<10%) and high risk (>40%) thresholds. The discrimination was compared to the Hepatic Steatosis Index (HSI) by both the C-statistic and net reclassification improvement (NRI) for the primary outcome and to both the HSI and the NAFLD fibrosis score (NFS) for the secondary outcome.

RESULTS:

100 pts (63% male, median age 35 years) were enrolled with 42 (42%) demonstrating NAFLD and 6 (6%) demonstrating hepatic fibrosis. Univariate risk factors for NAFLD are shown (Table 1). Older age, male gender, elevated BMI, and presence of hypertension were significantly associated with a diagnosis of NAFLD. A low-risk SLSI was 71% sensitive and a high-risk SLSI was 93% specific for a diagnosis of NAFLD. SLSI showed fair discrimination for NAFLD but this was not different from the HSI (C statistic 0.747 vs 0.722; NRI +0.02). For the diagnosis of hepatic fibrosis, a low-risk SLSI was 83% sensitive and a high-risk score was 90% specific. The SLSI showed fair discrimination (0.767) that was superior to both the HSI (C statistic 0.587, NRI +0.47) and the NFS (C statistic 0.688, NR +0.23).

CONCLUSION:

NAFLD was common among this South Asian cohort with CD despite few traditional risk factors. The SLSI has fair discrimination for both NAFLD and the more clinically relevant subgroup with hepatic fibrosis. Further steps include exploring alternate mechanisms for this finding and devising more sensitive CD-specific screening tools for NAFLD.
787 Addiction Medicine Consultation Reduces Narcotic Use and ER Visits and Increases Smoking Cessation in IBD Patients: A Cross-Sectional Study
Authors: Kudaravalli Praneeth , Michailidis Lamprinos , Kindred Michael , Akanbi Olalekan , Tripathi Nishant , Yarra Pradeep , Perry Courtney , Mullins Selina , Abomhya Ahmed Abdelsatar , Barrett Terrence
Published: October 2019

INTRODUCTION:

Inflammatory bowel disease (IBD) patients are chronically prescribed narcotics for chronic relapsing abdominal pain. We previously reported that emergency room (ER) visits in IBD patients increase the risk for chronic opioid use (COU - defined as 90 days of opioid use in a 6-month period) (Pauley et al Infl Bowel Dis 2017). Here we examine if referral to addiction medicine therapy reduces opioid prescriptions as well as ER visits.

METHODS:

IBD patients seen in the University of Kentucky out-patient GI clinic between January 2013 and November 2018 with COU were identified. Referrals to addiction medicine were identified by ICD 9/10 billing codes. EMRs of all study patients were retrospectively examined to collect data. Paired samples t-test was performed for outcomes 1 yr before and after addiction medicine consultation. All the statistical analysis was performed using SPSS Version 25 software; an alpha level of .05 was used throughout.

RESULTS:

During the 6-yr period, 2296 IBD patients on narcotics were identified. Among those 77 patients received addiction medicine referral, 36 patients complied. Mean age of the study population was 43 yrs. ER visits were reduced by 0.53 ± 0.24 visits in the year after consultation (mean ± SEM, 95% CI: 0.007–1.09; P < 0.04). Opioid prescriptions after addiction medicine consultation were also reduced by 0.37 ± 0.38 (P = 0.31). Substance abuse and mental health illnesses such as smoking, alcohol, illicit drug use, mood disorders and anxiety was seen in 72.2%, 22.2%, 19.4%, 27.8% and 16.7% of patients, respectively. Mean number of addiction medicine visits for tobacco and opioid abuse disorders were 2.2 and 5.3 respectively. Smoking cessation was successful in 11.5% of patients at 1 yr. However, a substantial reduction in smoking was noted in 26.9% of patients.

CONCLUSION:

Substance abuse and chronic opioids are factors known to be associated with worse outcomes in IBD patients. Our study shows IBD patients referred to addiction medicine service had significantly lower ER visits and trended to have fewer numbers of opioid prescriptions. Addiction medicine referrals were also successful in reducing smoking use by 27% with 11% cessation. Results reported here encourage further testing in larger sample sizes and suggest the implementation of addiction medicine professionals in the care of IBD patients.