bluuebunny/crossref_metadata_2025_split huggingface dataset:
P625 Electronic patient-reported outcomes in Inflammatory Bowel Diseases on vedolizumab therapy: Interim analysis of the non-interventional German LISTEN II study
Authors: Teich N , Stallmach A , Schulze H , Cavlar T , Knop J , Henneberger S 
Published: January 2024

Abstract

Background
Integrating systematic monitoring of patient-reported outcomes (PROs) with clinical information may enhance disease management and improve patient outcomes. Vedolizumab (VDZ) is approved for treating patients with ulcerative colitis (UC) and Crohn’s disease (CD). The German, multicentre, prospective, non-interventional LISTEN II study evaluates patient characteristics and effectiveness of VDZ treatment in real-world clinical practice, focusing on PROs.

Methods
Adult UC or CD patients, who either initiate VDZ intravenously (IV) or switch from IV maintenance to subcutaneous (SC) formulation, are enrolled. Data on patient characteristics, modalities of VDZ use and disease activity are recorded quarterly over one year. PROs are recorded via weekly questionnaires in app (ePRO). Sustained ePRO use was defined as proportion of patients reporting at least one PRO for ≥80% of available questionnaires. Interim data up to 9 months follow-up are presented.

Results
Data of 299 UC and 174 CD patients (51% and 59% female, respectively) with a mean age of 40 years were analysed. VDZ treatment was newly initiated IV (start) in 259 UC and 151 CD patients and switched from IV to SC application (switch) by 40 UC and 23 CD patients at baseline. Total mean pMayo score decreased in UC start-patients from 5.0 to 1.7 and from 1.1 to 0.8 in switch-patients. In CD start-patients HBI score decreased from 5.5 to 2.5 and from 3.1 to 2.3 in switch-patients.
The ePRO was initially utilized by 226 UC and 124 CD patients (51% and 61% female, 57% and 52% sustained ePRO users, respectively) with a mean age of 39 years; 86% were start- and 14% switch-patients. Disease activity at baseline was comparable to the overall population, showing a total mean pMayo score of 4.5 for UC and a HBI of 5.3 for CD patients. Most UC (82%) and CD patients (88%) used a patient support program for the first time. ePRO use declined to approx. 40% usage within the second quarter and to 30% during further follow-up.
Overall, mean symptom scores reported via the ePRO declined during the 9-month follow-up period. The most notable improvements (baseline to month 9) were reported for the symptom impact on work productivity (from 3.9 to 1.7 points) in UC patients and for sick leave (from 1.3 to 0.4 points) in CD patients (Table). For most PROs reduction in symptom scores was apparent within the first week of ePRO-use (Figure).

Conclusion
LISTEN II real-world data confirm VDZ effectiveness in UC and CD patients, with reduction in disease activity in IV starters and maintained effectiveness in IV-to-SC switchers. Both UC and CD patients reported sustained symptom improvement under VDZ treatment, with scores indicating improvement within the first week of ePRO-use.
P642 Effect of prior vedolizumab treatment on ustekinumab time-on-treatment in Crohn’s disease: a targeted literature review and statistical analyses
Authors: Owen G , Harvey R , Shields G , Jenkins A , Robertson J , Eaton J 
Published: January 2024

Abstract

Background
Ustekinumab, vedolizumab and anti-TNFα therapies are all biologics that are licensed to treat moderate-to-severe Crohn’s disease (CD). With many new therapies available in moderate-to-severe CD, the question of the optimal sequence in which to administer biologics becomes more pertinent. In this study, we aimed to determine if ustekinumab treatment effectiveness was affected by prior vedolizumab treatment in patients with CD.

Methods
We conducted a targeted literature review to identify evidence for ustekinumab effectiveness both with and without prior vedolizumab treatment. The population of interest was patients with moderate-to-severe CD treated with prior anti-TNFα. Studies were required to report single lines of treatment (e.g., specify second-line or state after one anti-TNF). Ustekinumab time-on-treatment (ToT) Kaplan-Meier (KM) data were recreated using digitisation methods and grouped into 2 categories (based on prior vedolizumab exposure) for subsequent statistical analysis. We compared ToT over a 34-month period (maximum follow-up period observed across all studies). A log-rank test was performed to identify whether there was a statistically significant difference in ToT between to the two groups across the follow-up period and Cox regression modelling was used to identify the direction of trends through estimation of a hazard ratio (HR).

Results
We identified 4 studies (n=495) that reported ustekinumab ToT after 1 anti-TNFα and 2 studies (n=69) that reported ustekinumab ToT after 1 anti-TNFα and vedolizumab. Based on the KM curves pooled across studies, the analysis showed the probability of remaining on treatment for ustekinumab following 1 anti-TNFα and vedolizumab was higher than following just 1 anti-TNFα. The log-rank test demonstrated a statistically significant difference between these two groups (HR=0.523; 95% CI: [0.310, 0.883]; log-rank p-value=0.014).
We identified a further 3 studies (n=1,017) that reported ustekinumab ToT after ≥1 anti-TNFα, and a further 2 studies (n=441) that reported ustekinumab ToT after ≥1 anti-TNFα and vedolizumab. Although these studies stated second line treatment of ustekinumab, some patients had received ≥2 prior anti-TNFα, which may have biased ToT results. There was no statistically significant difference in ToT for ustekinumab following ≥1 anti-TNFα and vedolizumab compared to following ≥1 anti-TNFα (HR=1.167; 95% Cl: [0.971, 1.1404]; log-rank p-value=0.098)

Conclusion
Our research shows that prior vedolizumab treatment does not negatively impact ustekinumab ToT in CD, which may have implications for the sequencing of biologics in moderate-to-severe CD and should be considered when deciding on the most appropriate treatment for patients.
P658 Safety and efficacy of MH002, an optimized live biotherapeutic product, for the treatment of mild to moderate ulcerative colitis: a first-in-disease, double-blind, randomized clinical trial
Authors: Vermeire S , Dewint P , Vansteelant M , Peterka M , Štěpek D , Kierkuś J , Wiernicka A , Napora P , Wolański Ł , Kopoń A , Magro F , Pinheiro I , Possemiers S , Haazen L , Bolca S 
Published: January 2024

Abstract

Background
Treatment options for patients with mild to moderate ulcerative colitis (UC) failing 5-ASA are limited. MH002 is an optimized consortium of 6 non-pathogenic, well-characterized commensal bacteria with immune modulating, wound healing and gut barrier protective effects. This study evaluated the safety, efficacy, and mechanistic effects of MH002 in mild to moderate UC.

Methods
In this 2:1-randomized, double-blind, placebo-controlled first-in-disease study (EudraCT 2020-001355-33), 45 patients with mild to moderate active UC (Modified Mayo Score [MMS] =4-8 but including Mayo Endoscopic Sub-score [MES] ≥2) received treatment with 400mg MH002 or placebo (PBO) once daily for 8 wks. Full colonoscopies with biopsies were performed at baseline and wk8, biopsies and endoscopy videos were scored by blinded central readers. The primary endpoint was the rate of treatment-emergent adverse events (TEAEs). Exploratory efficacy endpoints included clinical remission (MMS ≤2 with all sub-scores ≤1 and rectal bleeding sub-score =0), endoscopic improvement (MES ≤1), and UC-100 and biomarker normalisation (C-reactive protein [CRP] ≤5mg/L, faecal calprotectin [FCP] ≤250mg/kg). Changes from baseline (CFBL) in MES and stool consistency (Bristol Stool Form Scale) were also evaluated.

Results
MH002 was safe and well tolerated: a TEAE was reported in 11/31 (35%) patients with MH002 and in 8/14 (57%) with PBO. Most TEAEs were mild and unrelated to study treatment. Early discontinuations (7/45; 16%) occurred similarly in both groups. At wk8, patients achieved clinical remission, endoscopic improvement, and biomarker improvements at higher rates with MH002 vs PBO (Table 1). Clinical remission rates were 14% for MH002 vs 7% for PBO (Per-protocol Set [PPS]: 18% vs 0%). Significant differences in favour of MH002 over PBO were seen in the CFBL for MES at wk8 (P=0.05, 1-sided Wilcoxon) and for stool consistency at wk2 (P=0.0057, 1-sided Student t). In total, 14/45 (31%) and 36/42 (86%) patients had elevated CRP and FCP levels at baseline, resp. Of these, more patients treated with MH002 achieved normalisation at wk8 (CRP: 60% vs 25%; FCP: 36% vs 15%). Decreases in FCP and stool consistency with MH002 were observed as early as wk2 and were greater than with PBO through wk8 (Fig 1).

Conclusion
MH002 treatment was safe and well tolerated and resulted in clinically meaningful improvements in disease activity and inflammatory parameters. MH002 therefore represents a promising new treatment for mild to moderate UC patients insufficiently controlled with 5ASA. These results warrant further development in a phase 2/3 study.
P666 Accuracy of information given by ChatGPT for patients with Inflammatory Bowel Disease in relation to ECCO guidelines
Authors: Farrugia Y , Sciberras M , Gordon H , Furfaro F , Allocca M , Torres J , Arebi N , Fiorino G , Iacucci M , Verstockt B , Magro F , Katsanos K , Fenech V A , Chetcuti Zammit S , Ellul P 
Published: January 2024

Abstract

Background
As acceptance of AI platforms increases, more patients will consider these tools as sources of information. The ChatGPT architecture utilizes a neural network to process natural language, thus generating responses based on the context of input text. The accuracy and completeness of ChatGPT3.5 in the context of Inflammatory Bowel Disease (IBD) remains unclear.

Methods
In this prospective study, 38 questions worded by IBD patients were inputted into ChatGPT3.5. The following topics were covered: 1) Crohn’s Disease, Ulcerative Colitis, and malignancy, 2) maternal medicine 3) infection and vaccination 4) complementary medicine. Responses given by ChatGPT were assessed for accuracy (1 – completely incorrect to 5 – completely correct) and completeness (3-point Likert scale; range 1 – incomplete to 3 – complete) by 14 expert gastroenterologists, in comparison with relevant ECCO guidelines.

Results
In terms of accuracy, most replies (84.2%) had a median score of ≥4 (IQR:2) and a mean score of 3.87 (SD: +/- 0.6). For completeness, 34.2% of the replies had a median score of 3 and 55.3 % had a median score of between 2 and &lt;3. Overall, the mean rating was 2.24 (SD: +/- 0.4, Median:2 IQR :1). Though group 3 and 4 had a higher mean for both accuracy and completeness, there was no significant scoring variation between the 4 question groups (Kruskal-Wallis test p:&gt;0.05) (Table 1). However, statistical analysis for the different individual questions revealed a significant difference both for accuracy (p&lt;0.001) and completeness (p&lt;0.001). The questions which rated the highest for both accuracy and completeness were related to smoking, while the lowest rating was related to screening for malignancy and vaccinations especially in the context of immunosuppression and family planning.

Conclusion
This is the first study to demonstrate the capability of an AI-based system to provide accurate and comprehensive answers to real-world patient queries in IBD. AI systems may serve as a useful adjunct for patients, in addition to standard of care in clinic and validated patient information resources. However, responses in specialist areas may deviate from evidence-based guidance and the replies need to give more firm advice.
P670 Intestinal Motility Changes in Patients Undergoing Removable Stent Treatment for Focal Crohn’s Disease Strictures
Authors: Das R , Singh R , Menys A , Din S , Hoad C , Lund J , Cole A 
Published: January 2024

Abstract

Background
Management and assessment of fibrostenotic Crohn’s disease(CD) is a research priority. Deep phenotyping is key for effective therapeutic development. In this study, we explore MRI assessed bowel motility before and after endoscopic stent treatment of focal fibrotic strictures in patients with CD.

Methods
Patients (n = 12, median age = 51 y) undergoing removable stent treatment were recruited as part of an approved study. Average CD diagnosis was 31y (range 16-57 y). All strictures were fibrotic in nature- three were de novo, while the remaining were anastomotic (ileocolonic). All patients had symptoms attributable to focal stricturing. Each patient had an MR – Enterography (MRE) scan (median 21 weeks) before and after (median 17 weeks) stent dilation. MR – Enterography (MRE) protocol included oral preparation, anatomical and cine ‘motility’ sequences across the abdomen in 20s breath hold (1 image/second). Motility sequences were processed with CE/FDA cleared GIQuant (Motilent, UK) to produce a quantitative map from which, objective data could be generated across the bowel. Stricture assessment was performed by a consultant radiologist.
Non parametric statistics were used to investigate the following questions:
1. Was the baseline regional motility (mean, range) at stricture, dilation and morphologically normal bowel different across patients (Kruskal-Wallis)?
2. What were the changes in stricture motility pre and post stent placement (Wilcoxin Rank)?
3. Was stricture motility associated with stricture morphology (Spearman’s Rho)?

Results
1. Motility at the stricture (126, range 62 to 139), pre-stenotic terminal ileum (252, range 80 to 478) and the global small bowel (269, range 166 to 339) was varied across the cohort (P &lt; 0.001).
2. All patients had improvement in symptom scores & reporting, without change in stricture motility (P = 0.94).
3. A positive change in stricture motility was associated with reduced length of pre stricture dilatation (R = 0.64, P = 0.02)

Conclusion
Strictured intestine displayed reduced motility compared with adjacent bowel segments. While reduced, peristalsis was still present although paired analysis suggested no change pre and post stent stricture management. This implies that symptomatic relief was not related to altered peristalsis across the study. Finally, the length of dilation did appear to be associated with dynamic changes in stricture motility. In summary, as noted in stent-treated CD strictures, a dynamic physiological environment exists which can be captured with Cine MRI. These motility assessments, which have been studied as a proxy indicator of active CD, represent the first reported dynamic motility outcomes following stricture intervention.
P697 Short- and long-term outcomes following biologic use before non-conventional stricureplasty for Crohn’s Jejunoileitis
Authors: Belkovsky M , Cohen B , Sommovilla J , Hull T , Holubar S 
Published: January 2024

Abstract

Background
Non-conventional strictureplasties, specifically the Finney and Michelassi technique, are bowel-preserving surgical techniques for diffuse jejunoileal Crohn’s Disease (CD). We investigated the association of biologic use during non-conventional strictureplasty for Crohn's jejunoileitis and its short- and long-term outcomes.

Methods
We conducted a retrospective review of all patients with CD who underwent non-conventional strictureplasty at our centre, e.g., side-to-side antiperistaltic strictureplasty (SSAS) according to the Finney or modified Finney technique, or side-to-side isoperistaltic (SSIS) according to the Michelassi or modified Michelassi techniques from January 2000 to October 2022. Patients were categorized into BIO and NoBIO groups based on their uninterrupted use of biologics until the moment of surgery. Our outcomes of interest were: (a)30-day complications; and (b)surgical recurrence. Statistical analysis was performed using R version 4.3.1.

Results
A total of 71 patients underwent non-conventional strictureplasty: 80 SSAS and 14 SSIS. Group 1 had 17 patients in which 15 SSAS and 3 SSIS were performed. Group 2 had 54 patients in which 65 SSAS and 11 SSIS were performed. Most patients also underwent concurrent Heineke-Mikulicz strictureplasty in 49 patients (69%) and concurrent small bowel resection in 53 patients (74.6%). The patients in the BIO and NoBIO groups had similar baseline characteristics (Table 1). No differences were observed in perioperative outcomes (Table 2). No difference was observed when comparing surgical recurrence rates, but a longer median time to recurrence was observed in the BIO group (4.7 vs. 4.4 years, p=0.004).

Conclusion
Biologic use at the time of non-conventional strictureplasty for diffuse jejunoileal Crohn’s disease is safe and is associated with a longer median time to recurrence.
P698 Effectiveness and Safety of Ustekinumab for Ulcerative Colitis: A Brazilian Multicentre Real-World Observational Study
Authors: Parra R , Chebli J M F , Freitas Cardoso de Azevedo M , Chebli L A , Zabot G P , Cassol O S , Fróes R D S B , Santana G O , Lubini M , Magro D O , Imbrizi M , Moraes A C S , Teixeira F V , Alves Jr A J T , Gasparetti Junior N L T , Ferreira S D C , Queiroz N S F , Kotze P G , Féres O 
Published: January 2024

Abstract

Background
Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicentre cohort of Brazilian patients with UC.

Methods
We conducted a multicentre retrospective observational cohort study, including patients with moderate to severe UC (Total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of zero) within one year from baseline. Secondary endpoints included clinical response between weeks 12-16, endoscopic response within one year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety.

Results
A total of 50 patients were included (female, n=36, 72.0%), with a median disease duration of 9.2 years (1-27). Most patients had extensive colitis (n=38, 76.0%), and 43 (86.0%) were steroid-dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n=31; vedolizumab [VDZ], n=27). The co-primary endpoints of clinical remission and endoscopic remission at 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12-16 was 56.0%, endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 67.4%, and 50.0%, respectively. The UST treatment persistence rates at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and three patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-six adverse events (AEs) were reported, 15 of which were considered as serious AEs.

Conclusion
This is the first real-world experience study to report the effectiveness and safety of UST specifically in a Latin American population. In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST.
P699 Identification of A Novel Activated NK-Associated Gene Score Associated with Diagnosis and Biological Therapy Response in Ulcerative Colitis
Authors: Dong S , Zhang Y , Ye L , Cao Q 
Published: January 2024

Abstract

Background
Natural killer (NK) cells are associated with the pathogenesis of ulcerative colitis (UC), while their precise contributions remain unclear. The present study sought to investigate the diagnostic value of activated NK-associated gene score (ANAG score) in UC and evaluate its predictive value in biological therapy response.

Methods
Bulk RNA-seq datasets were obtained from the Gene Expression Omnibus (GEO). GSE11223, GSE87466, and GSE92415 were integrated for diagnosis value analysis. GSE206285 and GSE92415 were used to analyze the prediction of response to ustekinumab (UST) and golimumab (GLM), respectively. The immune infiltration landscape was estimated by single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. Differentially expressed genes (DEGs) correlated with activated NK cells were identified as activated NK-associated genes (ANAGs). Key ANAGs were screened by protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression.

Results
The immune infiltration analysis revealed a higher abundance of activated NK cells in non-inflamed UC tissues. 54 DEGs correlated with activated NK cells were identified as ANAGs. PPI analysis and LASSO regression were utilized to screen out 4 key ANAGs (SELP, TIMP1, MMP7, and ABCG2). ANAG score was established with the following formula: ANAG score = 0.628 * SELP + 1.574 * TIMP1 + 0.740 * MMP7 - 0.361 * ABCG2 – 18.940. The ANAG scores were significantly higher in inflamed tissues, as well as in biological therapy non-responders (NR) tissues before treatment. The ANAG score demonstrated excellent diagnostic value (AUC = 0.979). Furthermore, according to quartile stratification, patients with a higher ANAG score before treatment were more likely to experience lack of response to ustekinumab and golimumab.

Conclusion
This study established a novel ANAG score with the ability to precisely diagnose UC and distinguish the efficacy of biological treatment.