bluuebunny/crossref_metadata_2025_split 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.