bluuebunny/crossref_metadata_2025 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

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

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

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<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<0.0001). 34% (17/50) of the patients had necrotising-confluent granuloma, and 12% (6/50) had confluent (>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

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<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

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 >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<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

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

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 <115g/L in women and <130g/L in men. Iron deficiency was defined as Ferritin <30ug/L (<100ug/L if active inflammation – CRP >5mg/L, Faecal Calprotectin [FCP] >200ug/g) or Iron saturations <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<0.001) and FCP (n=314, SR -0.23 p<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<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

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 (< 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

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.
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

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<0.0001), PHRI (r=0.62, p<0.0001). In the rectum the RD score at all time points correlated significant with NHI (r =0,53, p<0.0001) and PHRI (r=0.63, p<0.0001). Similar correlation was seen in the sigmoid for NHI (r=0.51, p<0.0001) and PHRI (r=0.22, p0.0108). A RD score of <57.5 (Likelihood Ratio (LR) 4.176; AUC 0.7820 (95CI 0.7047 - 0.8593), p<0.0001) was associated with histological remission based on NHI (<2) and a RD score of < 64.5 (LR 9.821; AUC 0.8133 (95%CI 0.7053 - 0.9212), p<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

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

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

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 (<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 <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

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

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

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

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 (>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