bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0678 Iron deficiency, with or without anaemia, in Inflammatory Bowel Disease remains an undermanaged issue: Crohn’s Colitis Cure Data Insights Program
Authors: Pinnuck B , Su W K , Wilson W , Pipicella J , Ng W , Antoniades S , Walker G , Forbes A , Dutt S , Lynch K , Connor S J , Andrews J M 
Published: January 2025

Abstract

Background
Inflammatory bowel disease (IBD) increases the risk of nutritional deficiencies, particularly iron deficiency (ID), which is due to chronic blood loss from ulceration and intestinal inflammation causing increased iron demand and malabsorption. Reported rates of ID in IBD cohorts largely vary from 23-90% worldwide, influenced by age, gender, nutritional status, and comorbidities. ID can occur without anaemia and anaemia is not universally caused by ID.

Methods
Crohn’s Colitis Care (CCCare) is a cloud-based electronic medical record used in Australasia. Data feed into a deidentified clinical quality registry was interrogated in September 2024. People with IBD under active care (encounter within 14 months) were included to explore the prevalence of ID in this cohort. ID was defined as a serum ferritin level of &lt;30 mcg/L or a serum transferrin saturation &lt;16% with a serum ferritin level of &gt; 30 mcg/L. Anaemia was defined as a haemoglobin (Hb) of &lt;130 g/L in males and &lt;115 g/L in females.

Results
The 7493 eligible people with IBD, of whom 35.2% (n=2615) had iron studies (IS) (serum ferritin and transferrin saturation) and a Hb recorded. Their median age was 41 years (IQR 30 – 56) with an even gender distribution (50.1%, n=1310 female). Most resided in Australia (87.7%, n=2294) and 12.3% (n=321) in New Zealand. Crohn’s disease (CD) affected 60.3% (n=1578) of the cohort, ulcerative colitis (UC) 36.7% (n=961) and IBD-Unclassified (IBDU) 2.9% (n=76). ID was found in 25.4% (n=663) of those with IS, with rates comparable amongst IBD subtypes; 26.1% in CD, 23.7% in UC and 30.3% in IBDU. Of those with ID, 22.8% (n=151) had concurrent anaemia (24.3% (n=100) in CD, 20.6% (n=47) in UC, and 17.4% (n=4) in IBDU). In those with ID, the most common form of iron replacement was iron carboxymaltose (n=67, 69.8%), yet overall, only 96 of 673 (14.5%) with ID were documented to have been given iron replacement. The median C-reactive protein for those with IS was 2.3 (IQR 0.9 – 4.9), so the ID did not appear to be predominantly driven by a higher current inflammatory burden.

Conclusion
Despite being a well-known complication in IBD, which is easily treated, ID remains highly prevalent in routine care in this large real-world cohort. ID is more common than ID with anaemia, yet both ID and ID with anaemia are both likely to be impairing quality of life. Overall, there are low rates of iron replacement in this cohort. ID continues to be an area with significant opportunity to improve practice and outcomes. Protocolised screening and repletion may be needed to ensure consistency, and other approaches such as benchmarking or open data reporting on key point indicators may need to be implemented to drive change at scale.
P0686 Steroid use in patients with inflammatory bowel disease – claims data indicate a decline in steroid use for the first time over a five-year observation period in Germany
Authors: Bokemeyer B , Stratil A S , Friedrich B , Brunner P , Rath S , Papukchieva S 
Published: January 2025

Abstract

Background
Although maintenance and prolonged use of oral corticosteroids (OCS) in inflammatory bowel disease (IBD) is not recommended, it remains a common practice.1–3 This study evaluated the concomitant use and overuse of OCS among IBD patients in Germany from 2017 to 2022.

Methods
We retrospectively analysed German claims data (January 2017–December 2022). Patients over 18 years of age with continuous insurance and at least two quarterly diagnoses of Crohn’s disease (CD) and/or ulcerative colitis (UC) within two years were included. To increase the diagnostic certainty and clinical relevance, only patients with IBD who were currently receiving any form of IBD therapy (corticosteroids, aminosalicylates, calcineurin inhibitors, other immunosuppressants, biologics and/or small molecules) were included in the analysis. Oral corticosteroids (OCS) were defined as steroids for systemic use (ATC code: H02AB and H02BX). Concomitant use of an OCS use was assumed if a patient received a prescription for an IBD medication, excluding OCS monotherapy with OCS, alongside an OCS within the same quarter. OCS overuse was defined as receiving ≥2 OCS prescriptions within one year alongside an IBD medication. Subgroup differences were tested using Fisher’s exact test.

Results
The study identified 9,407 patients with confirmed CD and 11,772 patients with confirmed UC who were treated with IBD medications, during the observation period (Table 1). Of these, 42.8% of CD patients and 39.0% of UC patients were treated with concomitant OCS (CD vs. UC, p&lt;0.0001), while 31.3% of CD patients and 29.4% of UC patients experienced OCS overuse (CD vs. UC, p&lt;0.01) (Figure 1A). OCS use and OCS overuse decreased significantly from 2017 to 2022 in both CD and UC patients (p&lt;0.0001) (Figure 1B).

Conclusion
This study provides real-world insights into the patterns of (over)use of OCS in IBD patients. It highlights the continued over-reliance on OCS, particularly in CD patients. Notably, steroid overuse has decreased significantly over the 5-year observation period.

References
1.Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS). Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“. Published online August 1, 2021. Accessed September 11, 2024. https://register.awmf.org/de/leitlinien/detail/021-004
2.Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS). Aktualisierte S3-Leitlinie Colitis ulcerosa. Published online April 26, 2021. Accessed September 11, 2024. https://register.awmf.org/de/leitlinien/detail/021-009
3.Bokemeyer B, Ghiani M, Fuchs A, et al. Indicators of active disease and steroid dependency in patients with inflammatory bowel diseases not treated with biologics in a German real-world-setting. Int J Colorectal Dis. 2020;35(8):1587-1598. doi:10.1007/s00384-020-03588-w
P0689 A clinical study on the optimization of vedolizumab induction therapy for moderate to severe active Ulcerative Colitis at week 10
Authors: Li M , Xie Y , Tian F 
Published: January 2025

Abstract

Background
To observe the clinical efficacy of adding one dose of vedolizumab induction therapy in the 10th week for the treatment of moderate to severe active Ulcerative Colitis (UC), evaluate its effectiveness and safety, and provide clinical reference for the treatment plan of UC patients.

Methods
This study included a total of 80 UC patients who sought medical treatment at the Department of Gastroenterology at Shengjing Hospital of China Medical University from January 2020 to January 2025. They were divided into two groups: the experimental group (31 cases) received treatment with vedolizumab at weeks 0, 2, 6, 10, and 14, while the control group (49 cases) received treatment with vedolizumab at weeks 0, 2, 6, and 14 for at least 14 weeks. The changes in indicators such as modified Mayo score, Mayo endoscopic score, C-reactive protein (CRP), and safety analysis were observed before and after treatment in both groups. Clinical remission rate, clinical response rate, endoscopic remission rate, and endoscopic response rate were compared.

Results
The clinical response rate of the experimental group was 100%, significantly higher than the control group’s 84.62% (P&lt;0.05). The endoscopic response rate of the experimental group was 85.71%, significantly higher than the control group’s 57.50% (P&lt;0.05). There was no significant difference between the experimental group and the control group in terms of clinical remission rate and endoscopic remission rate (P&gt;0.05). The CRP levels before and after treatment were significantly reduced between the two groups (P&lt;0.05), and there was no significant difference in the number of patients with normal CRP levels between the groups (P&gt;0.05).

Conclusion
Adding vedolizumab induction once in week 10 can significantly improve clinical and endoscopic response rates, but more research is needed in terms of clinical and endoscopic response rates.
P0691 Impact of Ozanimod (OZA) on Circulating Neutrophils: Results from the Phase 3 Japanese True North (J-TN) Study of Patients (Pts) With Moderately to Severely Active Ulcerative Colitis (UC)
Authors: Zhang J , Gilvary C , Schwarz J , Uchikawa Y , Fujimoto G , Zhang C , Harris S 
Published: January 2025

Abstract

Background
OZA was approved for treatment (tx) of moderately to severely active UC in adults based on TN study results. Increases in circulating neutrophils are an indicator of systemic inflammation, and increased infiltration of activated neutrophils in intestinal mucosa contributes to mucosal inflammation in inflammatory bowel disease (IBD). Human neutrophil elastase-mediated degradation of calprotectin (CPa9-HNE) is a measure of neutrophil activity.

Methods
The effect of OZA on neutrophils and CPa9-HNE levels and the association of neutrophils and CPa9-HNE levels with OZA efficacy were assessed in all J-TN pts. During the 12-wk induction period, pts were randomized to OZA 0.46 mg, OZA 0.92 mg or placebo (PBO). OZA clinical responders at Week (W) 12 were continually assigned treatment to OZA or PBO for maintenance through W52. Circulating neutrophil and CPa9-HNE levels were analyzed at baseline and throughout the induction periods. Neutrophil and CPa9-HNE levels were explored by clinical response status at W12 and W52.

Results
Absolute neutrophil counts remained within the normal range throughout the induction and maintenance periods. Circulating neutrophil levels decreased with OZA 0.46 mg and 0.92 mg during induction and were significantly lower than those observed with PBO. Neutrophil levels significantly decreased by 2 weeks of treatment with OZA at 0.92mg dose groups compared to baseline. Circulating neutrophils remained low with continued OZA during induction period. Decreases in circulating neutrophil levels were greater in patients with clinical response starting at Week 9 (responders) than those without clinical response at Week 12 (nonresponders) in both dose Oza-treated pts groups during the induction period. CPa9-HNE levels also decreased with OZA 0.92 mg during induction period as compared with PBO and baseline. However, No significant difference of circulating Cpa9-HNE levels between responder vs nonresponser with Oza treatment at week 12. Baseline NEUT was positively associated with baseline stool frequency, 9-point Mayo and CRP. Baseline Cpa9-HNE levels was positively associate with baseline CRP. Furthermore, CfB NEUT was positively associated with CfB Physician Global Assessment, Rectal Bleeding and CRP with Oza 0.92mg treatment at week 12. CfB NEUT and Cpa9-HNE was positively associated with CfB CRP with both dose Oza treatments at week 12.

Conclusion
Circulating inflammatory markers of neutrophils and CPa9-HNE decreased with ozanimod use. These findings support the use of circulating neutrophils and CPa9-HNE, a measure of neutrophil activity, as pharmacodynamic markers for ozanimod treatment effect and potential disease markers in patients with UC.
P0693 The Chicago Mesenteric Fat Index: A Novel Biomarker for Assessing Inflammation in Pediatric Crohn’s Disease with Point of Care Intestinal Ultrasound
Authors: Kellar A , George T , Dolinger M , Smyth M , Krugliak-Cleveland N , Rubin D , St-Pierre J 
Published: January 2025

Abstract

Background
Pediatric Crohn’s disease (CD) is a chronic, progressive disorder that may result in lifelong disability. There is a need for tools that facilitate early detection and accurate assessment of disease. Point-of-care intestinal ultrasound (IUS) is an accurate and non-invasive tool that provides an alternative to magnetic resonance and/or computed tomographic enterography. In addition to bowel wall thickness (BWT) and hyperemia, mesenteric fat (MF) is one of the measures of CD severity visualized with IUS. Current guidance for grading MF is subjective and binary. We have previously proposed the Chicago Mesenteric Fat Index (CMFI) to standardize grading MF in adults, and demonstrated moderate to substantial inter-rater reliability (IRR). The aim of this study was to determine the IRR of MF assessment and validate the CMFI in pediatric CD.

Methods
IUS images of children with ileal CD were captured from November 2023 to May 2024. Those with prior surgery were excluded. CMFI differentiates severity based on the degree of wrapping: "none" (none or minimal MF wrapping), "incomplete" (incomplete circumferential MF wrapping with skipped areas along the terminal ileum), and "complete" (circumferential MF wrapping, continuous along the terminal ileum) (Figure 1). MF grading was performed by experienced pediatric intestinal sonographers, blinded to clinical data. IRR was analyzed using Cohen’s kappa statistic. We used population and clinical data and assessed the correlation of MF using chi-square for categorical data and Kruskal-Wallis for continuous variables.

Results
48 IUS examinations in 36 patients were included [50% female, 69% ileocolonic disease, predominately non-stricturing, non-penetrating in 67%]. Median BWT on IUS was 3.55 mm [1.9-5.25] (Table 1). Of the 48 scans, 32 (67%) had presence of MF wrapping,16 had incomplete MF wrapping and 16 had complete MF wrapping. The IRR for the binary assessment of MF was substantial (k = 0.6936), and grading according to the CMFI also showed substantial agreement (k = 0.6038). MF was associated with other IUS parameters, including BWT (p&lt;0.001 for both binary and graded index and binary), loss of bowel wall stratification (p = 0.001 for binary assessment and p = 0.002 for graded index) and the presence of hyperemia (p = 0.002 for binary assessment and p = 0.011 for graded index). MF was not associated with ileal strictures (p = 0.224 for graded index, p = 0.132 for binary assessment) (Table 1).

Conclusion
We demonstrate that IUS is a reliable tool for the assessment of MF in pediatric CD. MF assessment with the CMFI could be used as a potential objective non-invasive biomarker of CD severity in children, allowing for enhanced clinical decision-making and improved outcomes.
P0696 ADSS: A novel AI-derived metric for quantifying disease severity and extent in ulcerative colitis
Authors: Becker B , Fraessle S , Yao H , Luscher J , Girycki R , Machura B , Czornik J , Goslinsky J , Pitura M , Levitte S , Karrer T , Abbasi S , Arus Pous J , Fisher E , Bojic D , Richmond D , Bigorgne A , Prunotto M 
Published: January 2025

Abstract

Background
The Mayo Endoscopic Subscore (MES) is the prevailing standard for evaluating ulcerative colitis (UC) severity endoscopically, but correlates poorly with response to treatment. A comprehensive assessment encompassing both severity and extent is critical for monitoring treatment response in UC. Here we present the Aggregated Disease Severity Score (ADSS), a novel metric quantifying inflammation severity and extent in UC derived from the Ulcerative Colitis Severity Classification and Localized Extent (UC-SCALE) algorithm.

Methods
UC-SCALE was trained using 4,306 sigmoidoscopy videos from phase III etrolizumab clinical trials and consists of 1) preprocessing algorithms, 2) scoring algorithm that assigns MES score (0-3) to each frame, and 3) camera localization algorithm which maps each frame to an anatomical location. The ADSS is calculated by dividing the colon into 10 equal segments based on the location. An average MES score is computed for each segment, and these scores are summed to yield the ADSS (Figure 1 top) which ranges from 0 (all segments healthy) to 30 (all segments severely affected).

Results
UC-SCALE closely agrees (QWK = 0.83) with centrally-read MES. However, UC-SCALE’s spatially-resolved disease severity information showed clear treatment effects in groups of patients classified as endoscopic non-responders by the central reading score (CR); this was also reflected in the ADSS which showed decreased disease severity between screening and end-induction timepoints, but the CR was unchanged (Figure 1 bottom). Importantly, ADSS was more strongly correlated with fecal calprotectin than centrally-read MES (rADSS = 0.50 vs rCR = 0.37; Steiger’s Z-test Z = 3.10, p = 0.002).

Conclusion
UC-SCALE and ADSS provide a holistic disease evaluation by capturing both the severity and extent of inflammation. Together, these tools can be employed to improve the sensitivity of treatment response evaluation in clinical trials.
P0697 Ozanimod Inhibits Pro-Inflammatory Mediators of the IL-17 Pathway in the Tissues of Participants in the Phase 2 TOUCHSTONE Study
Authors: Zhang J , Chen X , Wu C , Petersen A K , Mehandru S , D’Haens G , Harris S 
Published: January 2025

Abstract

Background
OZA was approved for the treatment of moderately to severely active ulcerative colitis (UC). IL-17A, a proinflammatory cytokine, sustains the release of other inflammatory mediators and is associated with inflammatory bowel disease (IBD).

Methods
This analysis assessed gene expression from FFPE colon tissue in baseline and post treatment samples during TOUCHSTONE study. 197 Pts were randomized 1:1:1 to double-blind treatment with once-daily oral OZA 0.5 mg and 1 mg or matching placebo (PBO) for a 1-week (W) dose escalation period followed by 8W of induction treatment. Pts with clinical response at W8 (after dose escalation) entered a maintenance phase through W32. A NanoString whole transcriptome atlas (WTA) assay was run on these FFPE colon samples stained with antibodies to S1P1, panCK, and CD45. Six regions of interests (ROIs) were selected in each sample based on the staining and each ROI were split into two areas (CD45+ or CD45-). Differential enriched pathways analysis including IL-17 signaling pathway gene expression was analyzed in colon tissue samples collected before treatment, W8 and W32.

Results
OZA, not Placebo (PBO), induced significant PD spatial gene expression changes over time in colon tissue. No significant PD effects on gene expression changes were observed in CD45+ or Rest segment in PBO. OZA 0.5 mg induced significant spatial whole transcriptome gene expression changes at week 32 in the CD45+ segment (n=336 genes) or Rest (n=267 genes), and no differential expression genes were observed at week 8. OZA 1mg induced the most significant spatial whole transcriptome gene expression changes as early as W8 in segment CD45+ (n=121 genes) or Rest (n=171 genes). Significant overlap in OZA-included PD gene expression changes across doses, visits or cell types. OZA significantly downregulated 24 pathways in colon tissue from the CD45+ segment at W8 (p&lt;0.05), with IL-17 signaling as the most significantly downregulated pathway. Significant IL-17 related gene differences were identified with OZA treatment, including CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, MMP1, MMP3, MMP9, S100A8, S100A9, LCN2, CEBPB, HSP90B1 and IL1B genes, which involved in inflammation and immune response.

Conclusion
OZA led to circulating IL-17A reductions (previously reported) and IL-17 pathway related gene expression reduction in colon tissue, indicative of decreases in inflammatory responses. These finding may help support the use of supporting IL-17A and IL-17 pathway related genes as a good PD biomarker for OZA in UC.
P0700 Impact of filgotinib on health-related quality of life over 3 years in Japanese patients with Ulcerative Colitis: A post hoc analysis of the SELECTION and SELECTION long-term extension trials
Authors: Matsuoka K , Schreiber S , Hata E , Kaise T , Hibi T 
Published: January 2025

Abstract

Background
Filgotinib (FIL) is an oral, once-daily, Janus kinase 1 preferential inhibitor approved for the treatment of ulcerative colitis (UC). The efficacy and safety of FIL in adults with moderately to severely active UC were evaluated in the phase 2b/3 SELECTION trial (NCT02914522) and its long-term extension trial (SELECTIONLTE; NCT02914535). Previous analyses of the full populations in SELECTION and SELECTIONLTE demonstrated short- and long-term improvements in health-related quality of life (HRQoL) in patients receiving FIL.1,2 This post hoc analysis assessed the impact of FIL on HRQoL over 3 years in Japanese patients from SELECTION and SELECTIONLTE.

Methods
In SELECTION, patients received induction FIL 200 mg (FIL200), FIL 100 mg or placebo (PBO) for 11 weeks. At week 11, induction responders could enter the 47-week maintenance study. Patients who completed the SELECTION induction and maintenance studies (completers) and induction non-responders could enter SELECTIONLTE and continue their assigned dose (completers) or receive FIL200 (non-responders). This post hoc analysis included Japanese patients who received FIL200 or PBO in SELECTION, and Japanese completers and non-responders who received FIL200 in SELECTION and SELECTIONLTE. HRQoL was assessed over 3 years using the patient-reported outcome measures (PROMs) Inflammatory Bowel Disease Questionnaire (IBDQ), the EQ-5D and the 36-item Short Form Health Survey (SF-36).

Results
At week 10, a higher proportion of patients receiving FIL200 than PBO experienced minimal clinically important differences (MCIDs) in IBDQ score (77% vs 54%) and in the SF-36 mental component summary (MCS; 58% vs 21%) and physical component summary (PCS; 54% vs 36%) scores. MCID rates were similar between the groups for the EQ-5D value (49% vs 43%) and the EQ visual analogue scale (VAS) score (47% vs 57%) (Figure 1). MCID rates in each of the PROMs were maintained over 3 years of FIL200 treatment for SELECTION completers. In induction non-responders, MCID rates in most of the PROMs increased notably from week 10 and were maintained for up to 3 years of FIL200 treatment (Figure 2).

Conclusion
FIL200 treatment led to improvements (vs PBO) in IBDQ and the SF-36 scores, and maintenance or continuation of improvements in PROMs in SELECTION completers and induction non-responders over 3 years. These findings suggest that FIL200 has a positive short- and long-term impact on Japanese patients’ HRQoL and are therefore in line with findings from the overall SELECTION and SELECTIONLTE populations. Conclusions are limited by the small sample sizes.

References
1. Schreiber S, et al. J Crohns Colitis. 2023;17(6):863–875.
2. Feagan BG, et al. Aliment Pharmacol Ther. 2024;60(5):563–584.