bluuebunny/crossref_metadata_2025_split huggingface dataset:
P436 The AI based Red Density score is correlated with the established and new histological indices for Ulcerative Colitis in an independent cohort
Authors: Bossuyt P , Sinonquel P , John S , Shivaji U , Iacucci M , Nakase H , Van Aelst S , Pillai S , Abdawn Z , Sugita S , McCartney S , Armuzzi A , Bessissow T , Rath T , Yang D H , Vermeire S , De Hertogh G , Bisschops R 
Published: January 2024

Abstract

Background
Red Density (RD) is an automated endoscopic tool that is developed for the objective evaluation of disease activity in ulcerative colitis (UC). The initial development integrated histological disease activity based on Robarts histological index (RHI) in the machine learning algorithm. New histological scores for UC have been developed since.
The aim of this study was to establish the correlation between RD and the Nancy histological index (NHI) and PICaSSO Histologic Remission Index (PHRI).

Methods
Patients included in 4 centers in the ongoing PROCEED-UC study (NCT04408703) had assessment with RD in the rectum and sigmoid at baseline, w52 or early termination visit. Biopsies were taken according to protocol. Biopsies were scored for the Geboes score (GBS), RHI, NHI, PHRI in a blinded way after initial scoring convention training. Correlation was tested on patient level between mean RD per segment and the different histological indices based on Spearman correlation.

Results
In total 96 patients from 4 centers were included representing 2634 RD images from 400 colonic segments with biopsies and corresponding RD score. Mean (± SEM) rectal RD score was 32.7 (± 4.54), 33.69 (± 5.25) and 64.86 (± 31.71) at baseline, w52 and ET respectively. Mean sigmoidal RD score was 38.13 (± 3.68), 42.82 (± 11.80) and 77.33 (± 24.65) at baseline, w52 and ET respectively. Analysis based on the segment with the highest mean RD score per patient showed significant correlation with NHI (r=0.60, p&lt;0.0001), PHRI (r=0.62, p&lt;0.0001). In the rectum the RD score at all time points correlated significant with NHI (r =0,53, p&lt;0.0001) and PHRI (r=0.63, p&lt;0.0001). Similar correlation was seen in the sigmoid for NHI (r=0.51, p&lt;0.0001) and PHRI (r=0.22, p0.0108). A RD score of &lt;57.5 (Likelihood Ratio (LR) 4.176; AUC 0.7820 (95CI 0.7047 - 0.8593), p&lt;0.0001) was associated with histological remission based on NHI (&lt;2) and a RD score of &lt; 64.5 (LR 9.821; AUC 0.8133 (95%CI 0.7053 - 0.9212), p&lt;0.0001) with histological remission based on PHRI (=0). The current dataset demonstrated to be stable in line with the previously established RD cut-off with GBS and RHI. 1

Conclusion
In an independent cohort of patients with UC the correlation with the established and new histological indices for UC is confirmed. This underlines the value of RD as an objective endoscopic tool for the assessment of histological and endoscopic disease activity in UC.
Ref
1: Bossuyt P, Nakase H, Vermeire S, De G, Eelbode T, Ferrante M, et al. Automatic, computer-aided determination of endoscopic and histological inflammation in patients with mild to moderate ulcerative colitis based on red density. Gut. 2020;69:1778–86.
P449 Beyond a patient's control: assessing non-modifiable factors of transition readiness in IBD patients who have transferred to adult care
Authors: Bihari A , Kroeker K 
Published: January 2024

Abstract

Background
The transition from paediatric to adult care is an important time for a patient diagnosed with inflammatory bowel disease (IBD) in childhood/adolescence. A systematic review by Johnson et al., identified non-modifiable and modifiable factors that impact transition readiness. This review summarized positive associations with non-modifiable factors, such as females had higher self-management scores than males, patients with Crohn’s disease or a family IBD history associated with higher self-efficacy scores. Older age at diagnosis was associated with lower self-management scores in one study. Lack of or conflicting associations were found with respect to medication type and age at diagnosis. We aim to assess the prevalence of these non-modifiable factors in our patient population at time of transfer to adult care.

Methods
We conducted a medical chart review of patients with IBD who had their first adult care appointment between 2015 and 2022 at an academic IBD clinic in Alberta, Canada. We recorded information on non-modifiable factors, including gender, diagnosis, age at diagnosis, family history of IBD, and IBD medication type at time of first adult appointment. We used descriptive statistics to summarize the non-modifiable factors in our patient population.

Results
We reviewed the medical charts of 198 patients. The median age of IBD diagnosis was 14.4 years old (IQR: 13.0-15.9) with 2.5% of patients were diagnosed between 0-4; 6.1% between 5-9; 51.0% between 10-14; 40.4% between 15-17. At time of first appointment in adult care, 29.5% were on biologic monotherapy; 28.3% were on biologic combination therapy; 33.3% were on either 5-ASA or an immunosuppressant; the remaining 9.1% were either not on any IBD medications or medications were not documented. 43% of patients were female gender; while 60.0% of patients had Crohn’s disease; 6.6% had IBD-U, and 33.3% had ulcerative colitis. Further, 13.6% of patients had a first degree relative with IBD.

Conclusion
This study reports the prevalence of non-modifiable factors associated with transition readiness. By identifying these factors, we can direct more resources towards supporting specific populations in achieving transition readiness. For example, our study found that only 13.6% had a first degree relative with IBD – a factor positively associated with self-efficacy. This represents a large population without a relative with IBD that could benefit from resources designed to improve self-efficacy. Overall, this study supports future research aimed at designing interventions to improve readiness tailored to patients who may benefit the most.
P477 Performance of bowel preparation quality scales in patients with Crohn’s disease
Authors: Solitano V , Siegel C A , Korzenik J R , Maratt J K , Rex D K , Maguire B , Bressler B , Grossmann J , McDonald J W D , Remillard J , Shackelton L M , Feagan B G , Ma C , Jairath V 
Published: January 2024

Abstract

Background
The performance of bowel preparation (BP) in patients with Crohn’s disease (CD) is unknown and may be suboptimal due to the presence of mucosal inflammation, strictures, pseudopolyps and bowel resection. We evaluated the reliability and validity of available BP scales in patients with CD.

Methods
Bowel preparation, in colonoscopy videos (N=50) from patients with CD (N=40) that represented a range of bowel preparation quality and endoscopic disease activity, was independently rated twice, separated by at least 2 weeks, by 3 central readers using the Boston Bowel Preparation Score (BBPS), modified BBPS, Harefield Cleansing Scale (HCS), Food and Drug Administration bowel cleansing assessment scale (FDA BCAS), and a 100-mm visual analogue scale (VAS) of bowel cleanliness. Endoscopic activity was assessed with the Simple Endoscopic Score for CD (SES-CD). All assessments were on endoscope insertion and withdrawal and in the ileum, right colon, transverse colon, left colon, and rectum to facilitate evaluation of the relationship between BP and SES-CD scores. Reliability of BP assessment was quantified using the intraclass correlation coefficient (ICC) and interpreted with benchmarks defined by Landis and Koch.1 Validity was assessed by within-patient correlation between each BP scale and the VAS across segments using mixed effect models. Correlation between BP quality and SES-SD scores by location was assessed using Spearman’s rho.

Results
Substantial (ICC ≥0.61) inter-rater reliability was observed for all BP scales and the VAS during insertion and withdrawal, except for the FDA BCAS, which had moderate (ICC ≥0.41) inter-rater reliability on insertion (Table 1). Intra-rater reliability was similarly substantial for all BP scales and almost perfect (ICC ≥0.81) for the VAS during insertion and withdrawal.
Coefficients for the validity of all BP scales based on correlation with the VAS of bowel cleanliness exceeded 0.58 on both insertion and withdrawal. BP and endoscopic disease activity were negatively correlated in the colon, particularly in the left colon, suggesting that lower BP scores in this segment may result in higher SES-CD scores (Table 2).

Conclusion
Existing scales are reliable for the assessment of BP in patients with CD. These results provide a framework for scoring of BP quality in clinical trials for CD and support the inclusion of patients with CD for the evaluation of novel BP agents.
Reference:
1. Landis J.R. and Koch G. G. Biometrics. 1977:33;159-74
P504 Prevalence of gastrointestinal infections in ulcerative colitis patients assessed with QIASTAT-DX® GASTROINTESTINAL PANEL 2
Authors: Anolli M P , Liporace M F , Noviello D , Piazza O Sed N , Conforti F , Amoroso C , Teri A , Cariani L , Caprioli F , Vecchi M 
Published: January 2024

Abstract

Background
In inflammatory bowel disease (IBD), an acute clinical flare may be due to either disease exacerbation or an enteric infection. Thus, it is recommended to exclude infections before escalating IBD therapy. In this setting, conventional tests identify only a minimal proportion of infections (i.e. 10%). Whether nucleic acid multiplex tests can expand the range of detected pathogens and increase the overall prevalence is still a matter of debate.

Methods
We performed a single-center transversal prospective study at Fondazione IRCCS Policlinico Ca’ Granda. Stool samples from consecutive ulcerative colitis (UC) patients experiencing a disease flare and a group of patients in clinical remission were enrolled between February and October 2023 and tested with QIAstat-Dx Gastrointestinal Panel 2 (Qiagen GmbH, Hilden, Germany) for simultaneous qualitative detection and identification of nucleic acids from multiple viruses, bacteria, and parasites. Clinically active disease was defined as a Partial Mayo Score (PMS) of ≥2.

Results
Overall, 85 UC patients were enrolled. Demographics and clinical features are displayed in Table 1. Median age was 42 (18-79), 52% were males. The two most common treatment regimens were mesalamine (54%) and biologic/small molecule treatment (35%). 66 (78%) patients were clinically active, while 19 (22%) were in remission. In the active group, median bowel movements were 5 (3-15), 58 (88%) patients had loose stool, 32 (49%) reported abdominal pain, 40 (61%) urgency, 10 (15%) overnight symptoms, 6 (9%) fever. Median PMS was 5 (2-8). Median hemoglobin was 13.8 (8.2-16.4) g/dL, fecal calprotectin 508 (&lt;5-4980) ug/g. Prevalence of gastrointestinal infections with QIAstat-Dx was 30 vs. 10% (p=0.13) in active vs. remission group, respectively. The most common infections were: C.Difficile infection (CDI) (4 cases), Cytomegalovirus (CMV) (4 cases) and enteropathogenic E.Coli (EPEC) (4 cases). Regarding viral and E. Coli infections, clinical remission (PMS &lt;2) occurred spontaneously. As for CMV, Campylobacter spp., and CDI, all patients except one achieved remission following specific antimicrobial treatment. In one patient CMV infection led to hospital admission (circulating CMV DNA 35,395 IU/mL). The remaining patient did not receive specific antiviral therapy since sigmoidoscopy only detected isolated CMV+ cells, and remission was achieved with UC treatment escalation.

Conclusion
In UC patients experiencing a clinical flare, prevalence of gastrointestinal infections with QIAstat-Dx® Gastrointestinal Panel 2 is numerically higher than patients in remission. Further studies are needed to investigate whether increased detection could influence the clinical outcomes of IBD patients and time and costs for the healthcare system.
P552 Clinical factors associated with ustekinumab therapy persistence in a refractory Crohn’s disease cohort
Authors: Corcoran R , Breslin N , Ryan B , O'Connor A , O'Donnell S , McKiernan S , MacCarthy F , Dunne C , Hartery K , McNamara D , Kevans D ,   Trinity Academic Gastroenterology Group (TAAG)
Published: January 2024

Abstract

Background
Ustekinumab (UST) is a monoclonal antibody that binds to the p40 subunit shared by pro-inflammatory interleukins 12 and 23. UST has demonstrated efficacy for the induction and maintenance of remission in patients with Crohn’s disease (CD). A proportion of patients with CD do not respond to UST at the standard dose of 90 mg every 8 weeks.

Methods
A multi-centre retrospective study of CD patient who commenced UST therapy at two specialist tertiary referral centres between October 2012 and March 2021 was performed. Patient demographics, baseline characteristics, medication history and disease behaviour were characterised. Duration of UST therapy and UST dose escalation were documented. UST therapy persistence, was considered a proxy for treatment response, and was expressed as time to discontinuation of UST therapy. The study evaluated whether UST dose optimisation was associated with increased UST therapy persistence; and clinical factors associated with UST therapy persistence. Optimised dosing was defined as a dosing regimen of UST 90mg at less than an 8-weekly interval. Statistical analysis was performed using survival analysis and multivariate cox logistic regression with effect of covariates on outcome expressed as odds ratios (OR).

Results
133 patients commenced UST during the study period (age [mean, range] 39 years, 16-79; 59% female; disease duration [mean, range] 12.4 years, 1-35). 99% of patients had failed at least 1 biologic and 72 patients (54%) required dose escalation during the study period. The mean duration of UST therapy was 74 weeks (range 2-427). 75 (56%) patients were still receiving UST at end of study period. Survival analysis demonstrated that there was no significant difference in UST persistence between patients receiving standard and optimised UST dosing regimens, p=0.58. Patients with early UST dose optimisation (within 6 months of therapy initiation) had increased UST therapy persistence, p=0.003. A multivariate regression analysis demonstrated that early UST dose optimisation (within 6 months of therapy initiation) was independently associated with a longer time to UST therapy discontinuation (OR 0.31 (95%CI 0.15-0.68), p=0.003). Neither disease duration (OR 1.11, p=0.66), male sex (OR 0.91, p=0.83), concomitant immunomodulator use (OR 1.03, p=0.95), perianal disease (OR 1.09, p=0.85), smoking status (OR 1.16, p=0.68) nor previous surgery (OR 1.47, p=0.33) were independently associated with time to UST therapy discontinuation.

Conclusion
UST is an effective treatment for CD patients with prior biologic therapy exposure. Optimised UST dosing regimens are frequently utilised in routine clinical practice. There appears to be an increased likelihood of treatment success with early UST dose optimisation.
P587 Development and Characterization of a Novel Extended Half-life Monoclonal Antibody Drug Candidate Targeting Integrin ɑ4β7 for the Treatment of IBD
Authors: Zhu E , Rios D , Vaz R , Friedman J , Nguyen D , Spencer A , Shaheen H , Oh J 
Published: January 2024

Abstract

Background
Antagonism of the interaction between the cellular adhesion integrin ɑ4β7 and endothelial ligand mucosal addressin cell-adhesion molecule-1 (MAdCAM-1) is a safe and effective mechanism to treat Crohn’s disease (CD) and ulcerative colitis (UC). Additional benefit may be gained from an ɑ4β7 antagonist given via the subcutaneous (SC) route at extended intervals (eg, every 8 to 12 weeks) during maintenance therapy.

Methods
The novel humanized monoclonal IgG1 antibody SPY001 binds to the same ɑ4β7 epitope as vedolizumab and includes a YTE modification within the Fc region to increase half-life via increased affinity for the neonatal Fc receptor (FcRn), thereby favoring recycling into the circulation over degradation. Binding affinity of SPY001 to ɑ4β7 was determined by kinetic exclusion assay (KinExA) and flow cytometry, and functional activity was determined by inhibition of addressin-mediated cellular adhesion.

Results
SPY001 binds specifically to ɑ4β7 and not to the related integrins ɑ4β1 and ɑEβ7. In cellular assays, SPY001 binds ɑ4β7 on the surface of RPMI-8866 cells with an affinity matching that of vedolizumab, but it does not bind to Ramos cells expressing ɑ4β1. It demonstrates high affinity for ɑ4β7, with a KD of 836 pM as determined by KinExA. Functionally, SPY001 potently inhibits MAdCAM-1-mediated cellular adhesion with an IC50 comparable to that of vedolizumab but has no inhibitory activity for VCAM-1-mediated cell adhesion.

Conclusion
SPY001 is a novel humanized monoclonal IgG1 with high affinity for ɑ4β7 and potent inhibition of the ɑ4β7/MAdCAM-1 interaction. It offers the potential for effective and safe treatment of CD and UC with the advantage of infrequent SC dosing. Further preclinical and clinical studies are warranted to demonstrate this potential.
P592 Higher predictive power of epigenetic signatures for response to vedolizumab and ustekinumab in anti-TNF naïve patients with active Crohn’s disease
Authors: Van Zon S , Joustra V , Li Yim A Y F , Henneman P , Hageman I , de Waard T , Levin E , Noble A , Chapman T , McGregor C , Adams A , Satsangi J , de Jonge W J , D'Haens G R 
Published: January 2024

Abstract

Background
Despite the significant progress in IBD care with biological therapies, the current 'trial-and-error' method remains suboptimal. Previous results from our EPIC-CD study demonstrated that two distinct epigenetic panels of 25 and 68 DNA methylation markers, respectively, were associated with (non-)response to vedolizumab (VDZ) and ustekinumab (USTE) in active Crohn’s disease (CD)1. Data from clinical trials have demonstrated that response rates in patients naïve to biological treatment are higher. We therefore aimed to evaluate the performance of our models in bionaive and anti-TNF exposed subpopulations.

Methods
We prospectively measured peripheral blood DNA methylation profiles from 184 adult CD patients prior to treatment with VDZ or USTE in a discovery (n=126) and independent validation (n=58) cohort using the Illumina EPIC BeadChip array. Between 26 and 52 weeks, patients were categorized as responders or non-responders based on a combination of endoscopic response (≥50% reduction in SES-CD score), steroid-free clinical response (≥3-point drop in Harvey-Bradshaw Index (HBI) or HBI ≤4 AND no systemic steroids), and/or biochemical response (≥50% reduction in C-reactive protein (CRP) and fecal calprotectin or a CRP ≤5 g/mL and fecal calprotectin ≤250 µg/g). Epigenetic biomarker identification and classification analyses were conducted through stability selection gradient boosting on the discovery cohort. Subsequently, the performance of the identified epigenetic biomarkers was assessed independently on the validation cohort, with patients stratified by prior anti-TNF exposure.

Results
Out of the 58 patients in the validation cohort, 25 received treatment with VDZ, and 33 with USTE, with 52% (n=13) and 36% (n=12) respectively naïve to anti-TNF treatment. Baseline characteristics between anti-TNF naive and anti-TNF exposed patients showed no significant differences, despite a slight significant age difference in the vedolizumab group, where anti-TNF exposed patients were significantly younger (table 1).
In the overall independent validation cohort, the prediction models demonstrated an AUC of 0.75 for both VDZ and USTE. However, after stratification by prior anti-TNF exposure, we observed increased performance of our models among anti-TNF naive patients for both VDZ (AUCnon-exposed=0.85 versus AUCexposed=0.66) and USTE (AUCnon-exposed=0.97 versus AUCexposed=0.63 (figure 1).

Conclusion
Our findings demonstrate that prior anti-TNF exposure leads to somewhat reduced predictive power of our epigenetic models for Vedolizumab and Ustekinumab response. The predictive models may therefore find its optimal application in bio-naive patients, although they remain significant in anti-TNF exposed patients.
P608 Steroid use in a high proportion of IBD patients – first results from the Spanish cohort of the IBD-DICE study
Authors: Gomollón Garcia F , Vega Villaamil P , Romero Cara P , Michelena de Gorósabel N , Benyaich El Belghami G K , Huguet Malavés J M 
Published: January 2024

Abstract

Background
Corticosteroids (CS) have been an important therapeutic resource for treating inflammatory bowel disease(IBD) for the last 70 years. Guidelines still recommend CS in several clinical scenarios. Inadequate use of CS poses the patient at significant risks for irreversible side effects. However, the proportion of IBD patients with CS excess use in a real world setting, particularly in Spain, remains unclear. We aim to evaluate the proportion of Spanish IBD patients experiencing CS use/dependency as well as risk-associated factors.

Methods
IBD-DICE was a multicentre, international study to evaluate determinants and consequences of CS excess in IBD patients. In Spain, a total of 253 IBD patients (51% CD, 47% UC, 2% IBD-U) with quiescent or active disease were consecutively enrolled at 4 IBD-experienced sites from May to November 2021. Data on CS use (orally administered prednisone and/or budesonide) were captured by a web-based steroid assessment tool (SAT). CS dependency was defined as 1 or more CS courses within the last 12 months and/or no reduction of CS within the last 3 months without recurrent disease activity. SAT data were available for 253 IBD patients (56% were treated with ASA5, 29% with anti-TNF, 7,5% with IL-12/23 inhibitor).

Results
The majority of the 253 patients presented quiescent (64.43%,n=163/253) or mild (21.74%,n=55/253) disease activity rather than moderate (11.5%,n=29/253) or severe disease activity (2.37%,n=6/253). Of all patients, 17.8% (n=45/253) received at least 1 cycle of oral CS over the past 12 months (51.1% [n= 23/45] had moderate to severe disease). In fact, 65.7% [n =23/35] of the total patients with moderate to severe activity need CS. Of those 45 patients, 18 (45%) were treated for more than 3 consecutive months, one of them up to 13 months.
CS use was similar between UC patients (16.81%, n= 20/119) and CD patients (18.6%, n=24/129; p=0.75, Chi-square test). A third (31.1%, n=14/45) of all patients on CS had received 1 or more courses of CS and/or could not taper CS within 3 months after CS initiation. These patients were considered steroid-dependent of whom the majority (85.7%, n=12/14) had moderate to severe disease (table 1). Of the remaining 31 patients who tapered oral CS, 7 relapsed during the following 3 months.

Conclusion
We found that 17,8% of IBD Spanish patients are receiving CS, mostly in moderate to severe flares. CS-dependency was found in 31.1% of the patients, because of prolonged use (&gt;3 months) of the drugs. Long-term CS use is still common in practice, which could result in avoidable side-effects. Measuring CS dependency or excess in routine clinical practice is feasible and could form part of on-going quality improvement programs.
Table 1. Steroid use over the past 12 months