bluuebunny/crossref_metadata_2025_split huggingface dataset:
645 Black and White Patients With Inflammatory Bowel Disease Demonstrate Similar Biologic Use Patterns With Medicaid Insurance
Authors: Barnes Edward L. , Sandler Robert , Kappelman Michael , Long Millie D. 
Published: October 2019

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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