bluuebunny/crossref_metadata_2025_split huggingface dataset:
P283 Efficacy and safety of etrasimod in patients with moderately to severely active UC in Japan: Integrated analysis of the phase 3 ELEVATE UC 12 and ELEVATE UC 40 JAPAN trials
Authors: Takeuchi K , Hisamatsu T , Nakase H , Matsuoka K , Keating M , Yuasa H , Oe M , Arai S , Hibi T 
Published: January 2024

Abstract

Background
Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). We evaluated efficacy and safety among Japanese patients with moderately to severely active UC with contextualisation to the global population.

Methods
ELEVATE UC 40 JAPAN (NCT04706793) was a multicentre, double-blind, 40-week trial of patients from Japan who completed the 12-week phase 3 ELEVATE UC 12 induction trial (NCT03996369; study design described elsewhere1), resulting in a combined 52-week treatment period. Eligible patients were aged 16–80 years with documented history of inadequate/loss of response or intolerance to ≥1 approved UC therapies. Patients (hereafter the ‘Japan cohort’) continued baseline-assigned treatments from ELEVATE UC 12 (etrasimod 2 mg QD or placebo QD). Efficacy was assessed at Weeks 12 and 52 in patients with a Modified Mayo score (MMS) 5–9; the primary endpoint was clinical remission at Weeks 12 and 52. Pooled treatment-emergent adverse events (TEAEs) from ELEVATE UC 12 and ELEVATE UC 40 JAPAN were assessed up to Week 52.

Results
The Japan cohort comprised 32 and 16 patients receiving etrasimod and placebo, respectively; 28 and 14 patients with an MMS of 5–9, respectively, were included in the analysis. Baseline demographics were similar between treatment groups. A numerically higher proportion of patients receiving etrasimod vs placebo achieved the primary efficacy endpoint (Figure). Similar patterns were observed for all key secondary endpoints (Table). TEAEs occurred in 84.4% (27/32) and 62.5% (10/16) of patients receiving etrasimod vs placebo, respectively. The safety of etrasimod was similar between Japanese and global UC populations.

Conclusion
In this Japanese population, numerically higher proportions of patients achieved all efficacy endpoints with etrasimod vs placebo. Efficacy and safety findings were consistent with the global ELEVATE UC population.1

Reference
1. Sandborn WJ et al. Lancet 2023; 401: 1159–1171.
P312 Questionnaire survey for IBD patients in Japan; A Web-based J-CUP Survey
Authors: Goda Y , Matsumoto T , Imai K , Fujimitsu Y , Kajioka T , Kihara H , Funaki Y , Imaki S , Ueno M 
Published: January 2024

Abstract

Background
The prevalence of inflammatory bowel disease (IBD) in Japan has been increasing. We aimed to clarify the symptoms of patients with IBD in Japan using an internet-based questionnaire survey.

Methods
Overall, 805 patients with IBD were asked to complete an internet-based questionnaire addressing their history of disturbances in daily activities, prevalence of fecal urgency, incontinence, and treatment preferences.

Results
Responses were obtained from 447 patients with IBD (mean age: 54 years; 70% were men), comprising 363 patients with ulcerative colitis (UC) and 84 with Crohn's disease (CD). Notably, 16% of patients with UC and 35% with CD took over 1 year until the diagnosis of IBD, and 5% of patients with CD visited more than five medical institutions. Patients with CD were more likely to experience disturbances in their diet, work, travel, and outings than those with UC. Fecal urgency and incontinence were significantly more frequent in patients with CD than in those with UC (72% vs. 44%, and 50% vs. 26%, respectively). In contrast, 26% of the men and 37% of women with IBD had constipation. Acid reflux, sleep disorders, and depressive symptoms were present in approximately 30% of the patients. Oral administration was preferred.

Conclusion
Patients with IBD in Japan experience more severe disturbances in their daily activities, and these are more severe in those with CD than those with UC. In addition to fecal urgency and incontinence, care is required for constipation, acid reflux, sleep disorders, and depressive symptoms.
P342 Role of the Number and Location of Endoscopic Biopsies on the Detection of Granuloma in Patients with Isolated Intestinal Tuberculosis
Authors: Ye L , Fu Y , jiang Z , Cao Q 
Published: January 2024

Abstract

Background
Detecting granulomas is valuable for the diagnosis of isolated intestinal tuberculosis (ITB). However, how to perform an effective endoscopic biopsy remains unclear. We aimed to explore the impact of the number and location of endoscopic biopsies on granuloma detection in patients with isolated ITB.

Methods
A prospective analysis was conducted in 50 patients with confirmed isolated ITB who underwent predetermined endoscopic biopsy and pathological tests. 50 patients with isolated ITB were included for analysis. The diagnosis was confirmed based on microbiological, endoscopic, and histopathological evidences. For each patient, eight endoscopic biopsy specimens were obtained from either ulcer bases (n=4) or ulcer margins (n=4). After fixation, the specimens were serially sectioned into 8 slices on average. The slices were then stained and examined by an experienced gastrointestinal pathologist who were blinded to the patient information.

Results
The detection rates of granulomas from 2, 4, 6, and 8 biopsy specimens were 10, 28, 50, and 82%, respectively (5/50 vs 14/50 vs 25/50 vs 41/50, P&lt;0.00001). When 4 biopsy specimens were used, the granuloma detection rate with specimens from the ulcer base was significantly higher than that from the ulcer margin (41/50 vs 14/50, P&lt;0.0001). 34% (17/50) of the patients had necrotising-confluent granuloma, and 12% (6/50) had confluent (&gt;400 um) granuloma. In total, 205 granulomas were identified in 41 patients. Multi-granulomas were detected on 49 slices while mono-granulomas on were detected on 72 slices. 62.9% (129/205) of granulomas were detected in the ulcer base, 27.8% (57/205) in the lamina propria, and 9.3% (19/205) in the submucosa.

Conclusion
Using more than 8 or 4 biopsy specimens from the ulcer base improved the detection rate (over 50%) of necrotising or confluent granulomas for ITB. To improve the accuracy of diagnosis, clinicians should obtain ≥4 pieces of endoscopic biopsy from the ulcer base and conduct a deep biopsy into the lamina propria. Nevertheless, the integration of clinical characteristics and anti-TB responses is still required for suspected patients with undetected granulomas.
P366 Risk factors and outcomes of chronic antibiotic-refractory pouchitis in Korean ulcerative colitis patients: a single center retrospective study
Authors: Baek J E , Park J B , Bae J H , Kim M H , Hong S W , Hwang S W , Lee J L , Yoon Y S , Yang D H , Ye B D , Byeon J S , Myung S J , Yu C S , Yang S K , Park S H 
Published: January 2024

Abstract

Background
Chronic inflammation of the pouch after total proctocolectomy with ileal pouch-anal anastomosis (IPAA) remains a morbid complication in ulcerative colitis (UC). The goal of this study was to investigate risk factors and clinical outcomes of chronic antibiotic-refractory pouchitis (CARP) in Korean patients with UC.

Methods
This was a single center retrospective study on patients with UC who underwent total proctocolectomy with IPAA at Asan Medical Center in Korea between January 1987 and December 2022. CARP was defined as failure to respond to a 4-week course of a single antibiotic, needing more than 4 weeks of therapy with 5-aminosalicylates, steroids, immunomodulators or biologics/small molecules, while chronic antibiotic-dependent pouchitis (CADP) was defined as more than 3 episodes of pouchitis per year or persistent symptoms requiring long-term antibiotics to maintain disease remission. Primary outcomes were endoscopic remission defined as complete mucosal healing of chronic pouchitis and pouch failure defined as the requirement of diverting loop ileostomy or pouch excision. Univariable and multivariable logistic regression analysis were used to identify risk factors of CARP.

Results
A total of 251 patients were included and 232 were analyzed (Male, 57.3%; Current smoker, 13.4%; Median age at surgery, 44 years; Disease duration at surgery, 4 years; Previous exposure to biologics/small molecules, 23.7%; Extra-intestinal manifestations, 8.2%; Preoperative cytomegalovirus infection, 19.4%). The most common cause of surgery was steroid refractoriness (50.9%), followed by dysplasia/colorectal cancer (26.7%). The median time from surgery to chronic pouchitis was 48 months (interquartile range 23.5–100.0). Among 74 patients (31.9%) with chronic pouchitis, 31 patients (13.4%) were CARP and 43 patients (18.5%) were CADP. The most frequent endoscopic phenotype according to Chicago classification was focal inflammation of the pouch in all groups (chronic pouchitis, 47.3%; CARP, 35.5%; CADP, 55.8%). Patients with CARP were less likely to have concomitant probiotics compared with CADP (29.0% vs 72.1%; p&lt;0.01). Endoscopic remission rate in chronic pouchitis, CARP, and CADP were 14.9% (11/74), 9.7% (3/31), and 18.6% (8/43), respectively (Table 1). Pouch failure rate in chronic pouchitis, CARP, and CADP were 13.5% (10/74), 16.1% (5/31), and 11.6% (5/43), respectively (Table 1). In a multivariable analysis, current smoking status was positively associated with CARP development (OR: 3.56; 95% confidence interval 1.33–9.52; p=0.01).

Conclusion
Current smoker with UC who underwent IPAA had a higher risk of CARP. Concomitant use of probiotics was less likely to be associated with developing CARP.
P371 Calprotectin Testing: A Methods Comparison Study
Authors: Smith R , Bishara M , Nice R , Vine J , Chambers L , Roberts C , Kennedy N , McDonald T , Goodhand J , Ahmad T ,   Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group University of Exeter Exeter UK
Published: January 2024

Abstract

Background
In conventional laboratory-based Enzyme Linked Immunosorbant Assays (ELISA) for calprotectin measurement, raw stool is returned to and manually processed by testing laboratories. The OCS-Pledia calprotectin test uses the same stool collection device as the OCS-Pledia FIT test used in the UK Bowel cancer screening programme. In brief, individuals sample their stool with a picker and transfer to a preprepared buffered diluent, which is then returned to the laboratory for fully automated analysis.
We have previously shown that a stool concentration of &gt;100ug/g measured using the IDK calprotectin ELISA was the optimal cut-off to distinguish IBS from IBD (sensitivity 86%, specificity 90%, positive predictive value 39%, negative predictive value 99%).
We undertook a methods comparison study to report the stability, linearity and potential bias of the OCS-Pledia calprotectin assay compared with IDK ELISA.

Methods
32 stool samples were collected from people with GI pathology, and homogenised. Samples were prepared for calprotectin testing using IDK and OCS-Pledia less than 4 hours from excretion (mean2.6 [SD]1.3 hrs). Samples were left at room temperature and further extracts taken at 6, 24, 48, 72, and 168 hours. Pairwise analysis of samples across the reporting range was undertaken and linearity and bias assayed by Pearson’s correlation and Bland-Altmann analysis, respectively.

Results
Calprotectin was stable over one week in both the OCS-Pledia buffered and the IDK ELISA unbuffered stool samples. However, OCS-Pledia results showed lower variance than that of the IDK ELISA, especially at later time points. There was a linear relationship between calprotectin measured with the OCS-Pledia and IDK-ELISA assays (R2=0.85; p&lt;0.0001). The OCS-Pledia calprotectin assay has a positive bias across the reporting range. This led to 40 samples reading elevated calprotectin levels on OCS-Pledia but within normal range on IDK-ELISA. All 40 had colonic inflammation and therefore were false negative IDK-ELISA. Calprotectin concentrations of 600ug/g and 400ug/g measured using the OCS-Pledia assay were equivalent to concentrations of about 250ug/g and 100ug/g measured using the IDK ELISA.

Conclusion
OCS- Pledia assays for the measurement of calprotectin are likely to superseded conventional ELISAs because they are cheaper, easier to automate and do not involve laboratory staff pre-processing stool samples. Like conventional ELISA assays calprotectin is stable for at least one week. Clinicians will need to be aware, however, of the positive bias across the reporting range of calprotectin and adjust their positivity thresholds.
P377 Proportion of IBD patients with suboptimal control in daily clinical practice – real-world evidence from the IBD Podcast study
Authors: Dignass A , D'Amico F , Gomollón F , Bamias G , Magro F , Heatta-Speicher T , Michelena N , Leitner C 
Published: January 2024

Abstract

Background
Crohn’s disease (CD) and ulcerative Colitis (UC) are inflammatory bowel diseases (IBD) characterized by chronic inflammation of the digestive tract. Increasing evidence highlights the unmet need, the burden of disease, the progressive nature of the disease and subsequent intestinal damage, limited efficacy of current treatments and suboptimal disease management1-3. The IBD-PODCAST study aimed to estimate the proportion of patients with Crohn’s disease (CD) and ulcerative colitis (UC) with suboptimal disease control based on STRIDE-II4 criteria in a real-world setting across 10 countries.

Methods
A non-interventional, cross-sectional (with a limited retrospective component), multi-center, multi-country study was conducted in 2185 patients across 103 sites in Austria (n=111), Belgium (n=132), Canada (n=163), Germany (n=438), Greece (n=157), Italy (n=220), Portugal (n=130), Spain (n=396) Turkey (n=240) and UK (n=198). Criteria for suboptimal control were largely based on STRIDE-II4 and modified by an expert panel (Table 1) in order to evaluate disease control in this cross-sectional study.

Results
2185 patients (CD: n=1108, UC n=1077) with a mean age (SD) of 44.0 (14.8) years and mean disease duration (SD) of 12.4 (9.2) years were included (52.2% male). Ileal CD was present in 39.1% of patients and 35.3% of UC patients had extensive colitis. Among patients with CD and UC, 77.3% and 65.3% respectively, were on targeted immunomodulators (biologics or small molecule drugs) and, according to STRIDE-II4 -based therapeutic windows, 85.6% of CD and 85.4% of UC patients were assigned to the long-term (LT) treatment phase. At index point, suboptimal control at index was detected in 52.2% of patients with CD and 44.3% of patients with UC with relative consistency across countries. Impaired quality of life (QoL), clinically-significant EIMs, steroid overuse and signs of active inflammation in UC and CD, and fistulas in CD contributed most to the identification of suboptimal disease control in LT patients. More than one criterion indicating suboptimal control was seen in 37% of patients. Treatment optimization opportunities were observed in 49% of CD and 61% of UC patients on advanced therapy.

Conclusion
This study presents a high percentage of suboptimally-controlled IBD patients in a large multinational real-world cohort suggesting a large disease burden in IBD patients, a high unmet medical need and continuous requirements to improve standard of care in IBD. Future analysis should focus on monitoring and response to suboptimal control, and specific analysis of QoL in these patients.
P391 A not so innocent bystander: The prevalence and burden of anaemia at IBD onset
Authors: Rimmer P , Cheesbrough J , Ibrahim M , Hazel K , Javed A , Iqbal A , Regan-Komito D , Tull S , Love M , Cooney R , Quraishi M N , Iqbal T 
Published: January 2024

Abstract

Background
Anaemia is the most common systemic complication of Inflammatory Bowel Disease (IBD). Contemporary studies linking its prevalence with symptom burden at disease onset are limited. We present the prevalence and disability associated with anaemia in a large new onset adult IBD cohort.

Methods
Demographic, clinical and biochemical indices were collected prospectively in patients referred with suspected IBD between January 2021 - April 2023. Anaemia was defined as haemoglobin (Hb) of &lt;115g/L in women and &lt;130g/L in men. Iron deficiency was defined as Ferritin &lt;30ug/L (&lt;100ug/L if active inflammation – CRP &gt;5mg/L, Faecal Calprotectin [FCP] &gt;200ug/g) or Iron saturations &lt;15%. IBD disk scores were collected in a subgroup of patients. For two groups, non-parametric Mann-Whitney U tests were utilised, with a pairwise Dunn test and holm corrected p values for more than two.

Results
Hb results were available for 586 patients (182 CD, 170 UC, 234 non-IBD). Of these, an IBD disk score was available for 245 (84 CD, 71 UC, 90 non-IBD). Hb levels were significantly lower in CD than non-IBD (Table 1).
Overall, a significantly larger proportion of patients with CD were anaemic than UC (X2 10.2 p=0.001, odds ratio 2.4 [95% CI 1.39-4.16]). Whilst most anaemic patients in both groups were iron deficient, many without anaemia also had demonstrable iron deficiency (Figure 1).
In CD, Hb levels were significantly lower in ileocolonic disease than either isolated ileal (median Hb 125vs135.5g/L, p=0.002) or isolated colonic (125vs139g/L, p=0.002). Across IBD, Hb significantly correlated with Harvey Bradshaw Index (n=142, Spearman’s Rho [SR] -0.23 p=0.007), Partial Mayo (n=143, SR -0.23 p=0.006), Simple endoscopic score for CD (n=130, SR -0.29 p&lt;0.001) and FCP (n=314, SR -0.23 p&lt;0.001).
Regarding overall disease burden, Hb correlated with overall disability as determined by the IBD disk (n=155, -0.23 p=0.004). Anaemic patients had higher overall disability (total disk score 62.5vs49 p=0.007). Using individual disk domains, those with anaemia had higher fatigue (median 9vs8, p=0.012), disruption of education or work (7vs4, p&lt;0.001), impairment of body image (7vs4, p=0.019) and reduced sexual function (5.5vs1, p=0.004). When compared in a linear regression alongside age, body mass index, ethnicity, IBD type and baseline FCP, Hb was the second strongest predictor of overall disk score (Model fit R=0.515, BMI t=3.05 p=0.003, Hb t=-2.41 p=0.019).

Conclusion
Anaemia is frequently present at IBD onset, particularly in CD. Nearly half of those without anaemia have demonstrable iron deficiency. Severity of anaemia is associated with overall disease activity but influences symptom burden and disability beyond that which is attributable to mucosal inflammation alone.
P401 The diagnostic efficacy of the DETAIL questionnaire as a screening tool for spondyloarthritis in Korean patients with Inflammatory Bowel Disease
Authors: Kim S , Jun Y K , Choi Y , Shin C M , Park Y S , Kim N , Lee D H , Ha Y J , Yoon H 
Published: January 2024

Abstract

Background
The DETection of Arthritis in Inflammatory boweL diseases (DETAIL) is a very simple questionnaire consisting of six items. Developed in Italy as a screening tool for spondyloarthritis (SpA) in patients with inflammatory bowel diseases (IBD), it has not been validated in Asian patients with IBD. This study aims to assess whether the DETAIL questionnaire demonstrates appropriate screening properties in Korean patients with IBD.

Methods
Adult patients with IBD experiencing musculoskeletal symptoms were prospectively enrolled. An IBD specialist assessed them using a Korean-translated version of the DETAIL questionnaire, and referred them to a rheumatologist. The diagnosis of SpA was made based on the Assessment of SpondyloArthritis international Society classification criteria. The performance of the DETAIL questionnaire was evaluated using a Bayesian analysis model, with results graphically represented using Fagan’s nomogram.

Results
Eighty-seven patients with IBD (58 with ulcerative colitis and 29 with Crohn’s disease) completed the DETAIL questionnaire. Male was 50.1%, and the mean age of the patients was 39.1±12.1 years. Among these patients, 30 (34.5%) were diagnosed with SpA (20 peripheral, 10 axial). In the DETAIL questionnaire, items 1 (exploring peripheral synovitis), 2 (exploring dactylitis), and 3 (exploring Achilles enthesitis), which assess peripheral SpA, demonstrated good performance, especially with the highest positive likelihood ratio (LR+) found in item 2 (LR+ 3.26). Meanwhile, questions about inflammatory low back pain (items 4, 5, and 6), exhibited poorer performance, with LR+ values near or below 1. In subgroup analysis, the DETAIL questionnaire exhibited superior performance in younger IBD patients (&lt; 40 years old) across three items for peripheral SpA, compared to older IBD patients (≥ 40 years old). An affirmative response to at least two questions about peripheral arthritis yielded a posttest probability of SpA of 85% or more.

Conclusion
The DETAIL questionnaire demonstrates effective screening properties for detecting SpA in young Korean IBD patients.
P406 A novel active learning-based digital pathology protocol annotation for histologic assessment in Ulcerative Colitis using PICaSSO Histologic Remission Index (PHRI)
Authors: Santacroce G , Meseguer P , Zammarchi I , Del Amor R , Hayes B , Crotty R , Burke L , Ghosh S , Grisan E , Naranjo V , Iacucci M ,   PICaSSO group
Published: January 2024

Abstract

Background
Histologic remission (HR) is a critical treatment target in Ulcerative Colitis (UC). Among several scoring systems, the PICaSSO Histologic Remission Index (PHRI) simplifies HR assessment by evaluating the presence of neutrophils in the bowel tissue. Our artificial intelligence (AI) system built upon PHRI showed remarkable accuracy in HR assessment. PHRI assess neutrophils in four different regions of interest, so segmentation of these compartments is crucial to predict PHRI automatically. However, creating labelled histopathological datasets to train fully-supervised segmentation models takes time and effort. Hence, this study explores the impact of an active learning (AL) algorithm on enhancing image segmentation to alleviate the burden of detailed pathologists’ annotation and to standardise protocol annotation.

Methods
Biopsy samples from an international real-life prospective UC study were digitised into whole slide images (WSI). Initial annotations of superficial epithelium, lumen and epithelium of crypts and lamina propria for 33 WSI were employed to train a U-Net segmentation model at baseline. An AL framework was employed to iteratively select and annotate 15 unannotated images while selecting those with the highest uncertainty. Uncertainty was calculated using Least confidence sampling, Margin Sampling, and Shannon Entropy. The most informative samples, based on the average of the three uncertainty measure, were selected in consecutive batches of 5 images, and pathologists were enlisted in a human-in-the-loop process to refine annotations. Subsequently, the segmentation model was retrained by incorporating the newly refined annotated samples, and its performance was assessed using a fully annotated test set of 19 WSI.

Results
Following the baseline model training, the model’s segmentation performance assessed by the Dice score and Intersection over Union (IoU) was 0.622 and 0.386, respectively (see Table 1). Applying the AL algorithm with newly annotated images notably improved model performance, especially with 10 images (Dice=0.651, IoU=0.415). However, training the model with an additional 5 newly annotated images, which exhibited lower uncertainty, did not yield further improvement (Dice = 0.651, IoU = 0.415). Thus, the 10 annotated WSI demonstrating more uncertainty resulted crucial for the AL framework.

Conclusion
This novel AL-based iterative framework exhibits promise in standardising digital tissue annotation by our PHRI-based AI model. It offers a novel approach for both clinical trial and clinical practice, aiming to alleviate the burden of WSI labelling and reduce the bias of annotation, thereby improving histological assessment in UC.