bluuebunny/crossref_metadata_2025_split huggingface dataset:
P802 Probability of vedolizumab response as defined by clinical decision support tool is associated with lower healthcare utilisation in patients with Crohn’s disease
Authors: Dulai P , Wan Y , Huang Z , Luo M 
Published: January 2020

Abstract

Background
A clinical decision support tool (CDST) has been developed and validated for predicting treatment effectiveness of vedolizumab (VDZ) in Crohn’s disease (CD). We evaluated this tool’s ability to predict healthcare resource utilisation using real-world data.

Methods
CD patients treated with VDZ were identified using real-world data from the Optum (n = 358) and Truven MarketScan (n = 1445) databases. The full CDST with 3 clinical variables (prior bowel surgery, prior fistulising disease, prior TNF-antagonist exposure) and 2 lab values (albumin and CRP) was applied to the Optum dataset with available lab data, and patients were stratified into low (n = 27), intermediate (n = 152), or high (n = 179) probability of response groups. A modified weighting of the 3 clinical variables was created for application in Truven MarketScan due to the lack of availability of lab data. To assess the coherence with the full 5-variable CDST, the modified 3-variable CDST was used to stratify Optum patients into low (n = 137) or high (n = 221) probability of response, and then subsequently validated in the Truven MarketScan dataset (low, n = 510; high n = 935; response probability groups). Rates of hospitalisation, surgery, emergency department (ED) visits and annualised per patient costs were compared across response probability groups.

Results
Using the full 5-variable CDST, we observed a linear trend of significantly lower rates of ED visits, hospitalisation, surgery, and healthcare-related costs with increasing probability of response (Table). These results were consistent when using the modified 3 variable CDST in the Optum patient dataset where we observed a 3-fold higher rate of per patient healthcare costs in the low probability of response group compared with the high probability of response group ($6535 vs. $1900, p = 0.016). In the Truven patient dataset, the modified 3 variable CDST was also associated with a significantly lower rate of hospitalisation, surgery, and healthcare costs in the high probability of response group (Table). The majority of cost differences between high and low response groups was driven by costs related to hospitalisation and surgery.

Conclusion
A simple CDST can identify CD patients treated with VDZ who present a higher risk for healthcare resource utilisation, especially for hospitalisation and surgery. This tool could be integrated into population health monitoring algorithms using real-world data and offer flexibility on requirements of lab data.
P805 Patients with Crohn’s disease treated with ustekinumab vs. vedolizumab in real-world settings
Authors: Chiorean M , Jiang J , Candela N , Chen G , Romdhani H , Latremouille-Viau D , Shi S , Bungay R , Fan T 
Published: January 2020

Abstract

Background
Ustekinumab (UST) and vedolizumab (VDZ) are approved biologic therapies for moderate to severe Crohn’s disease (CD). Comparative data on real-world patient characteristics and healthcare costs for these drugs are scarce.

Methods
We examined healthcare costs associated with UST (healthcare common procedure coding system [HCPCS]: J3357, J3358, C9261, C9487, Q9989) and VDZ (HCPCS: C9026, J3380) in a retrospective cohort study of Truven commercial claims data (2009–2018) for adults with CD (international classification of diseases-9/10 codes: 555/K50). Eligible patients (18–89 years old) initiated UST or VDZ (index drug) on/after Sept 26, 2016, had CD as the latest relevant autoimmune disease on or before index drug initiation (index) date, ≥6 months of data available both before and after the index date, completed induction, and initiated maintenance therapy. Entropy balancing was used to address confounding factors (baseline characteristics). Primary outcome was healthcare costs assessed from a US payer perspective from index date to treatment discontinuation or end of follow-up (time on treatment). Cost were reported in 2018 US$ per patient per month and compared between treatment groups overall, and for biologic-naïve and -experienced (≥1 pre-index biologic therapy for CD) subgroups, using mean cost differences (MCD) obtained from weighted two-part models.

Results
The 599 (117 biologic-naive) UST- and 589 (172 biologic-naive) VDZ-treated patients who met eligibility criteria were similar in sex (54% and 57% female), mean age (41 ± 14 and 44 ± 14 years), time since diagnosis (42 ± 33 and 46 ± 35 months) and Charlson comorbidity index (0.4 ± 1.0 and 0.6 ± 1.1). Disease location, follow-up duration, and prior therapies and surgeries were also comparable. Characteristics were similar in biologic-naïve and -experienced patients. Mean weighted time on treatment was 11.4 and 12.1 months in UST- and VDZ-treated patients. Mean weighted total healthcare costs per patient per month was higher with UST vs. VDZ (MCD=$5051) driven by total index drug costs (MCD=$4946; Table). Cost differences were consistent in biologic-naïve and -experienced patients (total cost MCD=$4466 and $4836, both p &lt; 0.01).

Conclusion
Characteristics of UST- and VDZ-treated patients in real-world settings were comparable. In this population of patients receiving maintenance treatment for CD, index drug costs make UST treatment substantially more costly than VDZ. Further comparison of healthcare outcomes in patients treated with UST vs. VDZ is warranted.
P809 Increase of tuberculosis due to combination therapy in inflammatory bowel disease: a nationwide population-based study in Korea
Authors: Choi S J , Kim E S , Lee J M , Choi H S , Keum B , Jeen Y T , Chun H J 
Published: January 2020

Abstract

Background
Recent researches reported that inflammatory bowel disease (IBD) in Asia has become more prevalent. Since IBD is chronic inflammation disorder and its relapse is frequent, obtaining and maintaining remission is important. As our knowledge on the pathogenesis of IBD deepened, many immunosuppressants and biological agents were introduced and confirmed to be both safe and effective. However, biologics known as anti-tumour necrosis factor (anti-TNF) agents was reported to lose response over time in 23–46% of patients. Therefore, combination therapy adding immunomodulator drug such as azathioprine was introduced and showed better outcome by optimising biologic pharmacokinetics and minimising immunogenicity. Adversely, rates of tuberculosis are increased, but there is no large population data estimating and comparing these risk in combination therapy.

Methods
We used 2008–2016 data of the South Korean Health Insurance and Review Agency (HIRA), and odd ratio (OR) for tuberculosis in IBD patients who underwent anti-tumour necrosis factor (TNF) agent, azathioprine, or combination therapy.

Results
Between 2008 and 2016, 47,760 patients were newly diagnosed as IBD, 29,440 as UC and 15,320 as CD. We compared the risk of tuberculosis according to the medication divided into 5 groups; infliximab only, azathioprine only, combination of azathioprine and infliximab, azathioprine monotherapy and infliximab monotherapy, and azathioprine and infliximab whether simultaneously or separately. We also compared the risk between male and female. Hazard ratio of tuberculosis in infliximab monotherapy, azathioprine, and combination therapy in IBD patients were 1.132, 1.256, and 2.118, respectively.

Conclusion
Our study shows that Korean IBD patients are at risk for tuberculosis, and this results may highlight the importance of screening for tuberculosis in IBD patients.
P821 HLADQA1-HLADRB1 pre-emptive screening for azathioprine-induced pancreatitis in inflammatory bowel disease: a preliminary report
Authors: Wilson A , Wang Q , Gregor J , Chande N , Beaton M , Ponich T , Sey M , Yan B , Kim R 
Published: January 2020

Abstract

Background
Genetic variation in the HLADQA1-HLADRB1*07:01 haplotype is strongly associated with azathioprine (AZA)-induced pancreatitis in inflammatory bowel disease (IBD). We aimed to evaluate the utility of pre-emptive HLA DQA1-HLADRB1*07:01 screening to reduce the risk of AZA-induced pancreatitis in an IBD population.

Methods
A prospective cohort study is ongoing in IBD patients being considered for AZA therapy who are assigned to pre-treatment HLA DQA1-HLADRB1*07:01 (rs2647087) screening (n = 372 currently recruited) and compared with historical controls who have received AZA standard of care (n = 373). Participants in the pre-emptively screened group found to be variant carriers (AC or CC) are excluded from AZA treatment while wild type carriers (AA) received standard dosing. The incidence of clinically diagnosed pancreatitis (lipase &gt;3 times the upper limit of normal and one of abdominal pain or imaging findings suggestive of pancreatitis) occurring within 3 months in all participants with AZA exposure is being compared between the prospective and historic populations.

Results
The minor allele frequency of HLADQA1-HLADRB1*07:01 is 29%. To date, 194 participants (AA genotype) in the pre-emptively-screened cohort have received AZA therapy and completed the 3-month follow-up period. An additional 136 individuals with AA genotype are needed to obtain the target sample size (n = 330). Thus far, fewer cases of AZA-induced pancreatitis are seen in the pre-emptively screened population (pre-emptive cohort, 1/194 vs. historical controls, 13/373; odds ratio = 7.01, 95%CI = 0.91–53.98, p = 0.04).

Conclusion
Pre-emptive HLA DQA1-HLADRB1*07:01 screening may reduce the risk of pancreatitis during AZA treatment in patients with IBD. Completion of this study will help define whether HLA DQA1-HLADRB1*07:01 screening is a clinically-actionable and relevant tool for the safe use of AZA therapy in IBD.
P826 A predictive molecular classification developed in UC patients with active disease is observed consistently in a heterogeneous group of IBD patients
Authors: Kulmala K , Diaz O E , Huber S , Hedin C , Villablanca E J 
Published: January 2020

Abstract

Background
We have previously identified an unsupervised molecular classification of ulcerative colitis (UC) into two groups, UC1 and UC2, predictive of response to biologic therapy1. In that study, gene expression data in inflamed colonic biopsies from several published UC cohorts were used. UC1 is characterised by, for example, high expression of Cytochrome P450 26B1 (CYP26B1), calprotectin (S100A8) and interleukin 11 (IL11) and poor response to infliximab, which is also predicted by high expression of oncostatin M (OSM)2. In the current study the consistency of this classification was investigated in a heterogeneous group of inflammatory bowel disease (IBD) patients. Also, we sought to validate a quantitative polymerase chain reaction (qPCR) primer set as an alternative, more convenient methodology instead of microarray.

Methods
PCR primers for 7 differentially expressed genes that distinguished UC1 from UC2 in our microarray study were validated. OSM was also included. Separate gut biopsy samples (n = 44) from 15 patients, (8 Crohn’s disease, 7 UC), from different locations and at different time points, were analysed with qPCR.

Results
A heatmap of Pearson correlation coefficients (r) between gene expression levels and clinical factors for the pooled data was generated, Figure 1. Strong correlations, defined as 0.7 ≤ r ≤ 1.0, were found between OSM, CYP26B1, S100A8 and IL-11 (pairwise correlations were statistically significant, p &lt; 0.00001). Similar inter-gene correlations were also observed within individual samples, (data not shown). Gene expression levels were not associated with inflammation, Figure 1.

Conclusion
These data demonstrate that the group genes we have previously identified as predictive of response to biologic therapy in UC, (CYP26B1, S100A8 and IL-11) plus OSM are also concordantly up-regulated in biopsy material from heterogeneous patients. Thus not only patients with active UC, but also other forms of IBD may be sub-grouped according to this gene expression pattern. The capacity of this gene expression profile to predict therapeutic response should therefore be tested in a broader range of IBD patients. The fact that the concordance of the up-regulation of these genes was independent of inflammation per se, supports the clinical significance of this molecular clustering. Establishment of qPCR-based characterisation into UC1 and UC2 presents a more convenient methodology for clinical stratification.

References
P831 The role of adherent-invasive E. coli in pediatric Crohn’s disease: cause or effect?
Authors: Faqerah N , Logan Michael , Russell Richard , Gerasimidis Konstantinos , Walker Daniel 
Published: January 2020

Abstract

Background
The ability of adherent-invasive E. coli (AIEC), to adhere and invade intestinal epithelial cells and survive autophagy implicates them in the pathogenesis of Crohn’s disease (CD). Previous studies focused mostly on differences in the abundance of E. coli between patients with CD and healthy controls. Here, we studied changes in E. coli levels, E. coli strains and their ability to utilise carbon sources during treatment with exclusive enteral nutrition (EEN), at food reintroduction, and compared with healthy controls.

Methods
E. coli strains were isolated from culturing stool samples of twelve children with CD before and during induction treatment with EEN and following that, at food reintroduction. 10 healthy children acted as controls. 69 samples (CD, n = 59; healthy children, n = 10) were investigated in total. Absolute concentration of E. coli was measured with qPCR, changes in E. coli strains using colicin sensitivity spot tests and their ability to utilise carbon sources with Biolog phenotype microarrays.

Results
There was no significant change in the absolute levels of E. coli in patients with CD before or during EEN, and after food reintroduction. In comparison to healthy children, patients with CD had significantly higher levels of E. coli (p-value= 0.001). There were changes in E. coli at a strain-level in nine out of twelve CD patients as tested using colicin sensitivity tests before, during EEN, and after food reintroduction. Biolog microarrays showed a significant difference in E. coli community utilisation of 17 carbon sources in CD patients at different time points. Utilisation of polysaccharides, D-cellobiose, sucrose, and D-raffinose was increased during EEN compared with treatment initiation and after treatment cessation, at food reintroduction. In contrast, there was a significant reduction in utilisation for L-fucose and L-Rhamnose monosaccharides, sugar alcohols like D-glucose 6-PO4, and fatty acids such as propionic acid and acetoacetic acid by the end of EEN compared with treatment initiation and at reintroduction of habitual diet. In comparison to healthy controls, E. coli utilisation of different carbon sources in patients with CD was significantly different compared with CD patients during EEN only.

Conclusion
Children with CD experience changes in E. coli strains and in their ability to utilise certain carbon sources during treatment with EEN and compared with healthy controls. Analysis of strain-level metagenomic data will provide a comprehensive depiction of changes in E. coli population during EEN and compared with the healthy status.
P834 Effects of short-chain fatty acids supplementation on gut inflammation in DSS-induced murine colitis model
Authors: Eun C S , Han D S , Lee J G , Park C H 
Published: January 2020

Abstract

Background
Short-chain fatty acids (SCFAs) play an important role in maintaining gut homeostasis. However, inconclusive results exist whether administration of SCFAs ameliorates gut inflammation in patients with inflammatory bowel disease. We aimed to evaluate the effects of butyrate or mixture of SCFAs on gut inflammation in the dextran sulphate sodium (DSS)-induced murine colitis model.

Methods
Following oral treatment with 150 mM sodium butyrate or mixture of SCFAs (67.5 mM acetate, 40 mM butyrate, 25.9 mM propionate) for 2 weeks, acute colitis was induced in the C57BL/6 mice by adding 2% DSS to the drinking water for 7 days. Clinical activities including weight change and histologic findings of colonic segments were examined. Flow cytometry analysis was performed for analyzing regulatory T cells in the colonic lamina propria. To characterise the change of intestinal microbiota, high throughput Illumina MiSeq sequencing for sequential faces were performed.

Results
There were no significant differences in weight change, colonic length, and histological inflammation score between the DSS group, butyrate group, and SCFA mixture group. However, fluorescence activated cell sorter (FACS) analysis revealed that the expression of CD4+Foxp3+ regulatory T cells were increased in the butyrate and SCFA mixture groups than in the DSS group. Metagenomic sequencing analysis demonstrated that gut microbial profiles of the butyrate and SCFA mixture groups were significantly different from those of the control and DSS groups in PCoA. The relative abundances of the phyla Verrucomicrobia and Proteobacteria, species Akkermansia muciniphila and Escherichia fergusonii were increased in the butyrate and SCFA mixture groups than control and DSS groups.

Conclusion
Oral administration of butyrate or mixture of SCFAs resulted in changes in the gut microbial profiles and increased regulatory T cell expressions. However, gut inflammation was not alleviated by butyrate or SCFA supplementation in the DSS-induced murine colitis model.
P835 Correlation between microbial markers and faecal calprotectin in IBD patients
Authors: Amoedo Cibeira J , Ramió-Pujol S , Serra-Pagès M , Bahí A , Puig-Amiel C , Oliver L , Gilabert P , Clos A , Mañosa M , Cañete F , Miquel-Cusachs J O , Torrealba L , Busquets D , Sàbat M , Domènech E , Guardiola J , Garcia-Gil J , Aldeguer X 
Published: January 2020

Abstract

Background
Crohn disease (CD) and Ulcerative colitis (UC) are characterised by episodes of exacerbations and remissions. Monitoring disease activity based on intestinal lesion is mandatory prior to any change in the therapeutic strategy. Colonoscopy is the gold standard technique to monitor the disease activity in IBD patients, but it is usually discarded because of costs and risk issues. The concentration of Faecal Calprotectin (FC) is widely used as a non-invasive marker of inflammation of the intestinal mucosa, allowing the assessment of the disease activity. Recently, different studies have demonstrated that certain microbial species, part of intestinal microbiota which can be detected in stool samples, are capable of correlating with disease activity in CD and UC patients. The purpose of this study was to analyse the correlation between these microbial indicators and the FC to monitor the disease activity in CD and UC patients.

Methods
FC levels were used to define inflammatory disease activity, the predetermined cut-off of 250 μg/g of faeces was used, higher values indicated an active inflammation and lower values indicated disease in remission. Two cohorts consisting of 61 patients of CD (25 with active inflammation and 36 with remission) and 90 of UC (42 with active inflammation and 48 with remission) were recruited by the Gastroenterology department of 4 Catalan hospitals. A sample of faeces was collected from each patient. FC and the following markers were quantified by qPCR: Faecalibacterium prausnitzii (Fpra), Escherichia coli (Eco), Akkermansia muciniphila (Akk), Ruminococcus sp. (Rum), Bacteroidetes (Bac) and Methanobrevibacter smithii (Msm) for each sample.

Results
The bacterial markers presented different behaviour depending on the disease analysed. The abundances of Eco and Bac were higher in CD with active inflammation compared with CD with remission. In contrast, no significant differences were found for Fpra, Akk, Rum, and Msm. Besides, a significant positive correlation between Eco abundance and FC levels (0.280, p = 0.029) and a significant negative correlation between Msm and FC levels (−0.299, p = 0.021) were observed.
According UC patients, while the abundance of Eco was higher in patients with active inflammation, the abundance of Rum was significantly less abundant. No significant differences were found for Fpra, Akk, Bac, and Msm. Moreover, we also observed a significant negative correlation between Rum and FC levels (−0.308, p = 0.003, respectively).

Conclusion
The abundance of Eco and Msm in CD patients and the abundance of Rum in UC patients correlate to FC in order to determine inflammatory disease activity. So, these markers can also be an accurate discriminator of active disease in CD and UC patients.
P837 Changes in the intestinal microbiota of patients with inflammatory bowel disease during an 8-week infliximab infusion cycle
Authors: Seong G , Song J H , Shin J , Kong S M , Kim E R , Chang D K , Hong S N , Kim Y H 
Published: January 2020

Abstract

Background
This study investigated changes in the intestinal microbiota during 8-week infliximab maintenance therapy in inflammatory bowel disease (IBD) patients with clinical remission. Microbial compositional differences were analysed according to the trough level of infliximab (TLI) and mucosal healing (MH) status.

Methods
16S rRNA gene-based microbiome profiling was performed on 10 and 74 faecal samples from 10 healthy volunteers and 40 adult IBD patients, respectively. All enrolled IBD patients were in clinical remission during infliximab maintenance therapy. To identify changes in the intestinal microbiota, faecal sampling occurred at 1–2 weeks (1W) and 7–8 weeks (7W) after infliximab infusion. TLI was measured by ELISA at 8 weeks immediately before the subsequent infusion; MH was evaluated by endoscopy within 3 months.

Results
No significant differences were found in microbial composition, species richness, and diversity indices between 1W and 7W samples or in microbial composition and diversity between healthy volunteer and 1W or 7W samples. However, 7W faecal samples from the patients with TLI≥5 μg/ml showed increased species richness compared with TLI&lt;5 μg/ml, and patients with MH showed increased species diversity compared with non-MH. Beta-diversity analysis showed clustering between samples in the MH and non-MH groups. LefSe analysis identified differential expression of Faecalibacterium prausnitzii group between TLI &lt; 5 μg/ml and TLI ≥ 5 μg/ml and MH and non-MH groups.

Conclusion
There were no significant changes in the intestinal microbiota during an 8-week infliximab infusion cycle in IBD patients with clinical remission; however, microbial composition, species richness, and diversity were associated with TLI and MH status.