bluuebunny/crossref_metadata_2025_split huggingface dataset:
634 Transitioning From Vedolizumab IV to Vedolizumab SC in Patients With Ulcerative Colitis: Results From the VISIBLE Program
Authors: Wolf Douglas , Danese Silvio , Matthews Barbara , Jones Stephen , Chen Jingjing , Kisfalvi Krisztina , Sandborn William J. 
Published: October 2019

INTRODUCTION:
Vedolizumab (VDZ), a monoclonal antibody targeting α4β7 integrin, is approved as an intravenous (IV) formulation to treat ulcerative colitis (UC). In the first completed study with a new VDZ subcutaneous (SC) formulation (VISIBLE 1, NCT02611830, a randomized, double-blind, double-dummy, placebo-controlled, phase 3 trial assessing VDZ SC as maintenance treatment in adults with moderately to severely active UC), VDZ SC demonstrated statistically significant efficacy superior to placebo as maintenance treatment in patients with UC who had achieved a response to VDZ IV induction. The VDZ SC clinical program also includes an open-label extension (OLE, NCT02620046, ongoing). Analyses across these 2 studies allow for evaluation of efficacy when transitioning from VDZ IV to VDZ SC in patients who achieved clinical benefit with VDZ IV treatment for varying durations.

METHODS:
Efficacy of VDZ SC treatment after initial VDZ IV (300 mg) infusion was evaluated in 3 groups according to the duration of VDZ IV treatment before transitioning to VDZ SC (108 mg; Figure 1): (A) After 2 VDZ IV infusions (Week [W] 0 and 2) in patients who achieved clinical response at W6 and were randomized to VDZ SC maintenance treatment in VISIBLE 1; (B) After 3 VDZ IV infusions in patients who did not achieve clinical response at W6 who received a third VDZ IV infusion at W6 and had clinical response at W14 in VISIBLE 1 before enrolling in the OLE and transitioning to VDZ SC; (C) After 8 VDZ IV infusions (W0, W2, W6, and every 8 weeks thereafter until W52) in patients randomized to VDZ IV maintenance treatment in VISIBLE 1, completed 52 weeks of VDZ IV treatment, and transitioned to VDZ SC in the OLE.

RESULTS:
Patients who transitioned to VDZ SC after 2 infusions of VDZ IV (N = 106) had a clinical remission rate of 46.2% and a clinical response rate of 65.1% at W52. Among patients who received 3 VDZ IV infusions before transitioning to VDZ SC (N = 107), 39.2% achieved clinical remission and 48.0% achieved clinical response at W54 (14 weeks of IV; 40 weeks of SC). For patients who transitioned to VDZ SC after receiving 8 VDZ IV infusions over 52 weeks in VISIBLE 1 (N = 35), clinical remission and clinical response rates (both 76.9%) were maintained during the OLE on SC through W24 (Tables 1 and 2).

CONCLUSION:
Transitioning from initial VDZ IV treatment to VDZ SC maintenance treatment retains therapeutic benefit, independent of initial vedolizumab IV treatment duration.
638 Clinical Effectiveness of First-Line Anti-TNF Therapies and Second-Line Anti-TNF Therapy Post-Vedolizumab Discontinuation in Patients With Ulcerative Colitis or Crohn's Disease
Authors: Bressler Brian , Yarur Andres , Kopylov Uri , Bassel Marielle , Brett Neil R. , Lissoos Trevor , Lopez Claudia , Natsios Athanasios , Saha Sumit , Kifnidi Christina , Demuth Dirk , Patel Haridarshan , Mantzaris Gerassimos J. 
Published: October 2019

INTRODUCTION:
Real-world data is needed to understand and compare the clinical effectiveness of second-line (2L) anti-tumour necrosis factors (anti-TNF) treatment (Tx) post first-line (1L; biologic-naive) vedolizumab (VDZ) and 1L anti-TNF use in patients (pts) with ulcerative colitis (UC) or Crohn's disease (CD).

METHODS:
This was a real-world, multi-country, multi-centre retrospective study in UC and CD pts (≥18 years old) treated with 1L anti-TNF or 2L anti-TNF after discontinuation of 1L VDZ for any reason (received May 2014-March 2018). Pts were from sites in Canada, Greece and the United States. Anti-TNF therapies included adalimumab, infliximab, golimumab and certolizumab pegol. The index date was defined as date of 1L Tx initiation. Clinical effectiveness data were collected from 1L or 2L Tx initiation to earliest of death, chart abstraction date. Cumulative rates of Tx persistence, clinical response and clinical remission were estimated using the Kaplan-Meier method for UC and CD (separately and combined) over 6 months. Clinical response and remission were assessed using pre-defined hierarchical algorithms of standard disease measures reported in the medical records. P-values were generated using the log-rank test.

RESULTS:
This analysis included 579 anti-TNF patients (1L: 497 [UC: 224; CD: 273]; 2L: 82 [UC: 58; CD: 24]) from 36 sites. Proportions of patients in each cohort were: adalimumab (1L: 41.4%; 2L: 19.5%), infliximab (1L: 52.7%; 2L: 79.3%), golimumab (1L: 4.8%; 2L: 1.2%) and certolizumab pegol (1L: 0.8%; 2L: 0.0%). Mean (SD) age at index date: 1L, 39.6 (15.2); 2L, 49.4 (18.6) years, male: 1L, 49.9%; 2L, 61.0%, median (range: min-max) disease duration: 1L, 2.0 (<0.1–49.0); 2L, 3.7 (0.1–54.0) years. At 6 months, cumulative rates of Tx persistence (1L: 83.9%; 2L: 83.6%), clinical response (1L: 49.5%; 2L: 65.6%) and clinical remission (1L: 29.5%; 2L: 31.4%), were similar between 1L and 2L patients (Table 1). Results were similar when data were stratified by UC and CD (Table 1), albeit sample sizes were small.

CONCLUSION:
Cumulative rates of Tx persistence, clinical response and clinical remission were comparable between 1L anti-TNF patients and those who switched to a 2L anti-TNF following the discontinuation of 1L VDZ. Results suggest that 1L VDZ may not impact the effectiveness of subsequent anti-TNF Tx in real-world clinical practice. As 2L sample size was limited, these hypothesis-generating data warrant further study.
639 A Multimodal Intervention Reduces Intravenous Opioid Exposure Among Hospitalized Patients With Inflammatory Bowel Disease
Authors: Dalal Rahul S. , Palchaudhuri Sonali , Snider Christopher , Gitelman Yevgeniy , Brahmbhatt Mihir , Mull Nikhil , Mehta Shivan , Klock Christopher , Lewis James , Lichtenstein Gary R. 
Published: October 2019

INTRODUCTION:
Opioids (OPIs) are associated with increased mortality and infections in patients with IBD (AJG 2012;107(9):1409–22). Prior interventions targeting reductions in intravenous (IV) OPI exposure for all patients admitted to a general medical unit have decreased total OPI use without compromising pain control (JAMA IM 2018;178(6):759-63). We therefore performed a prospective evaluation of a multimodal intervention to reduce IV OPI exposure among IBD patients hospitalized at our institution.

METHODS:
This prospective study was conducted on a general medical unit at a large urban academic medical center from 1/1/19 to 5/31/19. Interventions to decrease IV OPI use were implemented in stages (Figure 1): 1. protocol for IV acetaminophen for IBD patients lacking enteral access 2. EHR “smartphrase” with analgesia guidance for use in gastroenterology consult notes 3. online IBD pain management pathway 4. automated text message alerts with analgesia guidance sent to providers. IV and total (IV+PO+TD) OPI exposures were measured in IV morphine mg equivalents (IVMME)/patient-day and compared to pre-intervention (1/1/18-12/31/18) data abstracted retrospectively from the EHR. IV acetaminophen and ketorolac use, length of stay (LOS), 30-day readmission rates (RRs), and pain scores (1-10 scale) were also assessed.

RESULTS:
Our study included 332 IBD patient encounters with similar baseline characteristics in pre-intervention (n = 241) and intervention (n = 91) periods (Table 1A). Between study periods, we observed a significant reduction in the proportion of patients receiving IV OPIs (43.6% vs. 30.1%, P = 0.03) and non-significant reductions in mean IV and total OPI exposures/patient-day (Table 1B). The proportion with highest OPI exposure (>39.0 IVMME/d, top quartile of non-zero total OPI exposure in 2018) was significantly reduced (13.7% vs. 5.5%, P = 0.04). Run charts were performed to correlate the timing of interventions to changes in OPI exposure (Fig 2). We observed appropriately increased IV acetaminophen use (0.8% vs. 14.3%, P < 0.01), similar mean pain scores (3.9 vs. 3.8, P = 0.74), non-significantly reduced IV ketorolac use (8.7% vs. 3.3%, P = 0.09), and significantly reduced mean LOS (7.2 vs. 5.2 d, P = 0.04) and 30-day RRs (21.6% vs. 11.0%, P = 0.03).

CONCLUSION:
A multimodal intervention successfully reduced IV OPI exposure for hospitalized IBD patients. This was associated with reduced LOS and 30-day RRs. Additional research is needed to determine long-term benefits of reduced OPI exposure in this population.
642 Effects of Ustekinumab Maintenance Therapy on Endoscopic Improvement and Histologic Improvement in the UNIFI Phase 3 Study in Ulcerative Colitis
Authors: Li Katherine , Friedman Joshua R. , Marano Colleen , Zhang Hongyan , Yang Feifei , Sandborn William J. , Sands Bruce E. , Feagan Brian G. , Peyrin-Biroulet Laurent , De Hertogh Gert 
Published: October 2019

INTRODUCTION:
Ustekinumab (UST) is an effective therapy for moderate-to-severe ulcerative colitis (UC), but its effects on mucosal healing (endoscopic improvement + histologic improvement) during maintenance treatment are unknown.

METHODS:
We evaluated the effects of maintenance UST on histologic and endoscopic activity in the UNIFI Phase 3 study of UST in moderate-to-severe UC (n = 961). Pts in response 8 weeks after receiving intravenous UST were randomized to receive maintenance treatment with subcutaneous (SC) placebo or UST 90 mg every 8 (q8w) or 12 weeks (q12w). Two colonic biopsies were collected from the distal colon at screening and Weeks 0 and 44 of maintenance. Endoscopic improvement (EI) was defined as a Mayo endoscopy subscore <1; histologic improvement (HI) comprised the following Geboes score-based criteria: absence of erosions or ulcerations, absence of crypt destruction, and <5% of crypts with neutrophil infiltration. To encompass both macro- and microscopic scales, histo-endoscopic mucosal healing (MH) was defined as achieving both EI and HI.

RESULTS:
At maintenance Week 44, EI was achieved in 28.6%, 43.6%, and 51.1% of pts treated with placebo, UST q12w (P = 0.002 vs placebo), and UST q8w (P < 0.001), respectively. HI was achieved at Week 44 in 32.9%, 54.0%, and 59.3% of pts treated with placebo, UST q12w, and UST q8w, respectively (P < 0.001 for both q12w and q8w). MH was achieved at Week 44 in 24.1%, 38.8%, and 45.9% of pts treated with placebo, UST q12w (P = 0.002), and UST q8w (P 0.001), respectively. HI at Week 44 (irrespective of maintenance treatment) was significantly associated with EI and MH (P < 0.001) and with both lower absolute levels and larger post-treatment changes in total Mayo score, partial Mayo score, and Mayo symptom sub-scores for stool frequency and rectal bleeding at Week 44. Both EI and HI following 8 weeks of UST treatment were associated with clinical remission and steroid-free clinical remission at Week 44 (P < 0.05), as well as remission through Week 44 (i.e., at both Week 8 and Week 44). For example, 26% of pts with induction HI were in clinical remission through Week 44, versus 4% of pts without induction HI. Induction MH was similarly associated with positive outcomes at maintenance Week 44.

CONCLUSION:
Among pts with moderately-to-severely active UC, those receiving SC UST maintenance had higher rates of EI, HI, and MH than those receiving placebo. Both EI and HI are associated with subsequent clinical remission and steroid-free clinical remission.
644 Incidence of Venous Thromboembolic Events in Patients With Ulcerative Colitis Treated With Tofacitinib in the Ulcerative Colitis Clinical Development Program
Authors: Sandborn William J. , Panés Julian , Sands Bruce E. , Reinisch Walter , Su Chinyu , Lawendy Nervin , Koram Nana , Fan Haiyun , Jones Thomas V. , Modesto Irene , Quirk Daniel , Danese Silvio 
Published: October 2019

INTRODUCTION:
Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). A safety signal for pulmonary embolism (PE) was seen in the tofacitinib 10 mg twice daily (BID) arm of an FDA post-marketing requirement study in rheumatoid arthritis designed to evaluate the long-term risk of major cardiovascular events and malignancy. Patients (pts) eligible for this ongoing, open-label, safety-endpoint-driven study had to be ≥50 yrs of age, have ≥1 cardiovascular risk factor and be on a stable dose of methotrexate. UC is a known risk factor for deep vein thrombosis (DVT) and PE.
1,2
We report the incidence of DVT and PE in the tofacitinib UC clinical program, as of Sep 2018.

METHODS:
DVT and PE events were evaluated from 4 randomized placebo-controlled studies (Phase [P] 2 and P3 induction studies [NCT00787202; NCT01465763; NCT01458951], 1 maintenance P3 study [NCT01458574]), and an ongoing, open-label, long-term extension (OLE) study (NCT01470612).
3–5
Three cohorts were analyzed: Induction (P2/P3 induction studies), Maintenance (P3 maintenance study), and Overall (pts receiving tofacitinib 5 or 10 mg BID in P2, P3, or OLE studies). Incidence rates (unique pts with events per 100 pt-yrs [PY] of exposure) were evaluated. For Overall Cohort analysis, pts were categorized based on the average daily dose of tofacitinib: predominant dose (PD) tofacitinib 5 mg or 10 mg BID.

RESULTS:
1157 pts were evaluated for DVT and PE, with 2404 PY of tofacitinib exposure and up to 6.1 yrs of treatment. In the Induction and Maintenance Cohorts, 2 pts had DVT and 2 had PE; all had received placebo in the study (Table 1). In the Overall Cohort, DVT occurred in 1 pt and PE in 4 pts during the OLE study; all pts had received PD of tofacitinib 10 mg BID. All pts with PE and DVT had risk factors for venous thrombosis (Table 1).

CONCLUSION:
In this post hoc analysis of pts with UC during tofacitinib exposure, 4 pts had PE and 1 pt had DVT, all of which occurred during the OLE study, in pts treated with PD of tofacitinib 10 mg BID (83% of Overall Cohort pts received a PD of tofacitinib 10 mg BID) with risk factors for venous thrombotic events. This analysis is limited by small sample size and limited drug exposure, and further study is needed.
647 Risk of New or Recurrent Cancer in Patients With Inflammatory Bowel Disease and Previous Cancer Exposed to Vedolizumab or Ustekinumab
Authors: Pang Alice , Hudesman David P. , Chang Shannon , Axelrad Jordan E. 
Published: October 2019

INTRODUCTION:
Previous studies have demonstrated that exposure to anti-TNFα and/or immunomodulators for inflammatory bowel disease (IBD) following a diagnosis of cancer was not associated with an increased risk of new or recurrent cancer. There is little data regarding the use of newer biologics, vedolizumab and ustekinumab, after a diagnosis of cancer. We aimed to investigate whether patients with IBD and a history of cancer who were subsequently exposed to vedolizumab or ustekinumab have an increased risk of developing new or recurrent cancer.

METHODS:
We reviewed the medical records of 5062 patients with IBD and cancer from an academic medical center between January 2013 and November 2018 to identify IBD patients who received vedolizumab or ustekinumab following a diagnosis of cancer. We collected demographic, IBD and cancer-related data. Our primary outcome was the development of new or recurrent cancer. Results were compared to historical data regarding the risk of new or recurrent cancer in patients exposed to anti-TNFα, an immunomodulator or no therapy for IBD following a diagnosis of cancer.

RESULTS:
We identified IBD patients who received vedolizumab (n = 59) or ustekinumab (n = 18) monotherapy following a diagnosis of cancer (Table 1). The median age at cancer diagnosis was 51 years (IQR 43-65) for vedolizumab and 57 years (IQR 55-66) for ustekinumab. During a median follow-up of 68 months (IQR 21-132) for vedolizumab and 48 months (IQR 12-96) for ustekinumab, 3 (5%) and 3 (17%) patients developed subsequent cancer, respectively. Compared to historical data, there were differences in subsequent cancer risk between exposure groups (Figure 1; log-rank 0.001). However, when adjusted for stage of prior cancer, compared to no therapy, there was no difference in risk of new or recurrent cancer between patients exposed to vedolizumab (HR 0.01, 0.01-7.58), ustekinumab (HR 0.85, 0.11-6.50), anti-TNFα (HR 0.60, 0.34-1.07) or immunomodulators (HR 1.01, 0.58-1.75) following a diagnosis of cancer.

CONCLUSION:
In this single-center study, exposure to vedolizumab or ustekinumab in patients with IBD and a history of cancer conferred a low risk of new or recurrent cancer. Exposure to vedolizumab or ustekinumab monotherapy was not associated with an increased risk of subsequent cancer compared to historical data of exposure to anti-TNF, immunomodulators or no immunosuppression following a diagnosis of cancer. Larger studies are needed to confirm these findings.
648 Outpatients With Inflammatory Bowel Disease Are More Likely to Have Viral and Multiple Enteric Infections Identified on Multiplex PCR Pathogen Panel Testing
Authors: Hong Soonwook , Main Michael , Hine Ashley M. , Hudesman David P. , Chang Shannon , Axelrad Jordan E. 
Published: October 2019

INTRODUCTION:
Gut microbial dysbiosis and impaired mucosal immunity play a major role in the pathogenesis of inflammatory bowel disease (IBD). Previous research has shown that IBD patients experience greater disease burden from gastrointestinal infections. The increasing availability of gastrointestinal multiplex polymerase chain reaction stool panels (GI PCR) has allowed for the rapid and accurate identification of viral, bacterial, and parasitic pathogens not readily diagnosable with conventional stool testing. We aimed to characterize the burden and risk factors for gastrointestinal infections on outpatients with and without inflammatory bowel disease presenting with symptoms of acute gastroenteritis.

METHODS:
We performed a cross-sectional review of outpatients presenting with gastroenteritis to an academic medical center from September 2015 to March 2019 who received a FilmArray GI PCR. Baseline demographics, presence of IBD and disease characteristics, risk factors including travel history, sexual activity, HIV status, and symptoms on initial presentation were recorded. The primary outcome was the detection of an enteric pathogen. Secondary outcomes include the class of pathogen detected, i.e., viral, bacterial, parasitic. T-test and Chi-square analysis were used to compare outcomes between groups.

RESULTS:
We reviewed 815 outpatients who received GI PCR testing, of whom 94 (12%) were diagnosed with IBD. Patients with IBD were more likely to present to the initial visit with bloody diarrhea (46% vs. 8%, P < 0.001), hematochezia (15% vs. 6%, P = 0.001), and fever (23% vs. 9%, P < 0.001; Table 1). Of outpatients with IBD, 33 (35%) had a gastrointestinal pathogen detected compared to 216 (30%, P = 0.190) of non-IBD outpatients. Patients with IBD were more likely to have viral (28% vs. 18%, P = 0.044) or multiple pathogens (11% vs. 6%, P = 0.028) and less likely to have bacterial (61% vs. 73%, P = 0.920) and parasitic infections (0 vs. 6%, P = 0.382) on GI PCR (Table 2). There were no statistically significant differences in gender, race, travel history, sexual activity, HIV status, or rate of pathogen detection between patients with and without IBD.

CONCLUSION:
Enteric infections were common in outpatients with and without IBD. IBD patients presented with more viral and multiple pathogens on GI PCR testing compared to non-IBD controls. Further studies are needed to investigate the impact of these different enteric pathogens on clinical management and disease burden.
651 Bridges to Excellence (BTE) Quality Indicators in Inflammatory Bowel Disease (IBD) in Gastroenterology Fellows' Clinic at the University of Oklahoma Health Sciences Center: A Quality Improvement Project
Authors: Salem George , Ali Ijlal , Grossen Alyssa , Bitar Hussein , Kastens Donald J. 
Published: October 2019

INTRODUCTION:
The American Gastroenterology Association (AGA) Bridges to Excellence (BTE) Inflammatory Bowel Disease (IBD) Care Recognition program encourages clinicians to develop a superior quality of care in the management of IBD. The compliance to AGA quality metrics has been historically low in general gastroenterology (GI) clinics. We evaluated adherence to BTE measures in the care of IBD patients seen at a tertiary care hospital gastroenterology fellows' clinic, and developed a provider-friendly template to further increase compliance.

METHODS:
Patients with diagnosis of IBD (Crohn's disease (CD), Ulcerative Colitis (UC), or indeterminate colitis (IC)) were identified in the gastroenterology continuity clinic using ICD-9 and ICD-10 codes at the University of Oklahoma Health Sciences Center, Gastroenterology fellow's clinic. Baseline patient characteristics and 8 BTE measures were recorded. Based on compliance with quality metrics, a simple, provider-friendly template was added to GI initial and return clinic notes. Overall adherence to BTE measures and average scores as per the AGA 100 point scale were evaluated and compared pre- and post-intervention.

RESULTS:
50 patients were seen in GI fellows' clinic over 6-month period in the pre-intervention phase, and 35 were seen in the post-intervention phase. Baseline characteristics for both groups were similar. Overall adherence to BTE measures was 54%, and average BTE score was 58.8 (3 star) in the pre-intervention phase. Overall adherence to BTE measures was 42.4%, and average BTE score was 53 (3 star) (P > 0.05) in the post-intervention phase. On sub-group analysis, it was found that only half of the patients had had the intervention implemented for their care (18/35). Sub-group analysis of patients where template was implemented, adherence to BTE measures was 98.4% and average BTE score was 98.5 (5 star) (P = 0.02). When compared to the group of patients where template was not used, the overall adherence was 42.4%, and average BTE score of 53 (3 star). This was found to be statistically insignificant when compared to pre-intervention group (P = 0.60).

CONCLUSION:
The care for IBD patients continues to be a multi-disciplinary, complex approach. Using template increased compliance to vaccination and tobacco screening/counselling in our cohort. Using a provider-friendly template may improve compliance with AGA quality metrics for the care of IBD patients in outpatient settings.