bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0484 Impact of Early Aggressive Treatment on Long-term Biochemical Marker Patterns in Inflammatory Bowel Disease: A latent class mixed model
Authors: Jun Y K , Choi Y , Shin C M , Park Y S , Kim N , Lee D H , Ahn S , Yoon H 
Published: January 2025

Abstract

Background
Inflammatory bowel disease (IBD) shows a highly variable disease course, making early identification of patients at risk for poor outcomes important for personalized treatment. This study aimed to classify the long-term disease course in patients with IBD using biochemical markers and to investigate the clinical factors associated with different disease trajectories.

Methods
Longitudinal data on C-reactive protein (CRP) and fecal calprotectin (FCP) levels were collected from patients in a tertiary hospital cohort between 2017 and 2023. Patients with at least two CRP and FCP tests between six months and five years after IBD diagnosis were included. Early IBD-related treatments, ER visits, and hospitalizations were defined as occurring within six months of diagnosis. A latent class mixed model (LCMM) was employed to identify the distinct subclasses based on CRP or FCP changes. Subsequently, univariate analyses and multinomial logistic regression were conducted to evaluate the relationships between different biochemical trajectories and clinical variables.

Results
Among the patients, 245 with CD and 635 with UC were included in the CRP model, while 256 with CD and 536 with UC were included in the FCP model. Through LCMM, a three-class model was found to be most appropriate for patients with both CD and UC: Class 1, characterized by early and sustained biochemical remission; Class 2, featuring delayed remission; and Class 3, marked by prolonged difficulty in achieving remission for over five years. In the CRP trajectory analysis, early initiation of immunomodulators (IM) in patients with CD was significantly associated with a higher probability of belonging to Class 1 (Class 2 vs. 1, odds ratio [OR] 0.344; Class 3 vs. 1, OR 0.472; p-value = 0.039). In the FCP trajectory analysis, early advanced therapy (AT) significantly increased the odds of belonging to Class 1 for patients with CD (Class 2 vs. 1, OR 0.383; Class 3 vs. 1, OR 0.220; p-value = 0.004). Conversely, no significant factors were identified in the CRP trajectory analysis for patients with UC. In UC, younger age at diagnosis (Class 2 vs. 1, OR 0.969; Class 3 vs. 1, OR 0.980; p-value = 0.004) and early IM initiation (Class 2 vs. 1, OR 2.928; Class 3 vs. 1, OR 2.698; p-value &lt;0.001) were associated with higher odds of belonging to Class 2 or 3, whereas current smoking was associated with a higher likelihood of belonging to Class 1 in the FCP trajectory analysis (Class 2 vs. 1, OR 0.194; Class 3 vs. 1, OR 0.559; p-value = 0.008).

Conclusion
Early aggressive treatments, particularly the prompt initiation of AT in CD, may contribute to achieving long-term biochemical remission; however, similar associations were not observed in UC.
P0486 Acceptability of fecal calprotectin in patients with inflammatory bowel disease: impact of an alternative collection device for stool sampling
Authors: Pasi G , Antari A , Masson D , Dejoie T , Caillon H , Collins M , Bourreille A , Le Berre C ,   Institut des Maladies de l’Appareil Digestif (IMAD) Hépato-Gastro-Entérologie et Assistance Nutritionnelle Inserm CIC 1413 Nantes Université CHU Nantes F-44000 Nantes France.
Published: January 2025

Abstract

Background
Fecal calprotectin (FC) is a key non-invasive biomarker used to monitor inflammatory bowel disease (IBD). Despite its clear clinical value, patient adherence to the test remains suboptimal, mainly due to reluctance related to stool collection. The objective of the ACCALMI study was to compare the acceptability of a new stool collection device, similar to the one used for fecal immunochemical tests (FIT), with a standard stool container, and to evaluate its impact on patient compliance.

Methods
In this prospective, single-center study, 156 patients with an established diagnosis of IBD and who had been prescribed a FC test as part of their routine care, were randomly assigned to either the standard container group or the alternative device group (Procise Stool Collection Device™), which includes a collection tube with a thin spiral-shaped probe facilitating stool collection. Acceptability was assessed using a 4-category ordinal scale (from “poor” to “very good”) and a visual analog scale (VAS, from 0 to 10). Analyses were conducted in both per-protocol and intention-to-treat (ITT) populations, with missing data handled using the maximum bias method. Factors associated with improved FC acceptability, and compliance with FC testing, were analyzed.

Results
The alternative stool collection device significantly improved acceptability compared to the standard method, both on the ordinal scale (OR 2.69, p &lt; 0.001) and the visual analogue scale, although for the latter it did not reach the predefined threshold of a 30-point difference (95% CI: 19.7 to 44.7). ITT analysis showed similar results. Embarrassment and discomfort associated with the standard container were alleviated by the alternative device. Long home-hospital distances (&gt;50 km) and use of the alternative device were the only factors significantly associated with better acceptability in multivariate analysis. Compliance was similar between the two groups and remarkably high (92%).

Conclusion
The ACCALMI study demonstrated that the alternative stool collection device, similar to the one used in FIT, is more accepted by IBD patients than the standard container, thus improving the acceptability of FC testing. These findings support the integration of patient-centered innovations in diagnostic and follow-up testing to improve the monitoring of IBD.

Funding
This study was partially funded by Takeda®

Acknowledgments
Collaboration with Biosynex®.
P0488 The course of Crohn’s Disease in the Biologics Era: an in depth Single-Center Tertiary Cohort Study in Belgium
Authors: Vuckovic C , Cremer A , Minsart C , Bottieau J , Franchimont D , Liefferinckx C 
Published: January 2025

Abstract

Background
Since 1999, Biologics have become a cornerstone in the management of Crohn’s Disease (CD), enabling complete mucosal healing in a significant proportion of patients, with measurable changes in major outcomes in large phase III/IV clinical trials. This holds true particularly when patients were exposed early at diagnosis to biologics, as reported in the recent PROFILE study. However, their real-world impact on the long-term course of the disease remains uncertain. This retrospective study aims to characterize the natural history of CD before and during the biologic era, in a single tertiary center in Belgium.

Methods
Based on inclusion criteria, 516 CD patients were included and stratified in two subpopulations, according to the date of CD diagnosis (before or after 1999). All events were recorded from date of diagnosis to maximum follow-up (FU), to achieve high granularity, from disease characteristics to treatment adaptations. Statistical analyses were performed using Prism.

Results
Among 516 CD patients included, 87 and 429 were diagnosed before and after 1999, respectively. There was no significant difference in demographics or disease characteristics at diagnosis. Patients diagnosed after 1999 were exposed to biologics for a larger portion of their FU compared to those diagnosed before 1999 [51% vs 11%, p&lt;0.0001]. At maximum FU, more patients diagnosed before 1999 had progressed to B2/B3 phenotypes (69% vs 39%, p&lt;0.0001), reflecting their longer disease duration compared to patients diagnosed after 1999 (Median FU 27 years [22-30] vs 12 years [6-15], p&lt;0.0001). Indeed, 10 years after CD diagnosis, disease progression to B2/B3 phenotypes was similar in both groups (27% vs 23%, p=0.6), (Figure 1a). Changes in phenotype were diagnosed sooner in patients diagnosed after 1999 compared to those diagnosed before 1999 (Median 4.8 years [1.8-9.9] vs 12.3 years [6-16.8], p&lt;0.0001] (Figure 1b). They were also operated sooner than patients diagnosed before 1999 (Median 5.9 years [2.1-10.2] vs 12.5 years [6.6-18.2], p&lt;0.0001] (Figure 1c).

Conclusion
The proportion of patients progressing to a B2/B3 phenotype at 10 years of disease course is similar for CD patients diagnosed before and during the Biological Era. The detection of complications occured earlier in patients diagnosed after 1999, which suggests a shift toward more proactive monitoring since the advent of biologics. Based on these findings, it remains uncertain whether biological therapies have significantly altered the course of the disease and phenotype progression in CD patients. However, while these results are based on objective outcomes, they do not fully capture the impact of biological treatments on patients quality of life and disease burden.
P0491 Cumulative Inflammatory Burden and Structural Bowel Changes as Independent Risk Factors for Colonic Dysplasia in Ulcerative Colitis: A Case-Control Study
Authors: Park D , Oh J E , Choi S , Park J , Park S J , Cheon J H , Kim T I , Park Assistant professor J J 
Published: January 2025

Abstract

Background
Long-standing inflammation has been implicated in the development of colonic dysplasia in ulcerative colitis (UC). However, the relationship between varying degrees of inflammatory exposure and dysplasia risk remains poorly understood. We aimed to identify risk factors for colonic dysplasia in UC patients, with particular focus on quantifying long-term inflammatory exposure.

Methods
In this retrospective single-center case-control study, we reviewed 55 UC patients diagnosed with colonic dysplasia (low-grade, high-grade, or cancer) between 2013 and 2022, and 110 randomly selected UC patients without dysplasia as controls. Endoscopic inflammation was scored using the Mayo endoscopic subscore (0-3), and cumulative inflammatory exposure was calculated by multiplying these scores with the duration of each endoscopic follow-up period. Clinical factors and endoscopic findings were compared between groups, and logistic regression analysis was performed to identify independent predictors of dysplasia.

Results
Univariate analysis showed that the dysplasia group had significantly higher frequencies of anemia (hemoglobin &lt;10 g/dL), elevated ESR (&gt;18 mm/hr at diagnosis), steroid and biologics use, tubular or shortened colon, and high cumulative endoscopic inflammation scores (&gt;10). In multivariate analysis, after adjusting for age, gender, and disease duration, both tubular or shortened colon (OR 3.172, 95% CI: 1.029-9.780) and high cumulative endoscopic inflammation score(&gt;10) (OR 4.205, 95% CI: 1.065-16.600) were independently associated with increased dysplasia risk.

Conclusion
High cumulative inflammatory burden, as indicated by elevated endoscopic inflammation scores and structural bowel changes, significantly increases the risk of colonic dysplasia in UC patients. More intensive surveillance strategies may be warranted for patients with these objective risk indicators to enable early detection of colitis-associated dysplasia.
P0496 Upadacitinib for Patients with Crohn’s Disease and Previous Biologic Failure: A Systematic Review and Meta-Analysis
Authors: Campedelli L , Perim V , Hueb R 
Published: January 2025

Abstract

Background
Upadacitinib is an oral Janus kinase 1 (JAK1) inhibitor that has demonstrated potential as a therapeutic agent for Crohn’s disease (CD). This systematic review and meta-analysis aim to evaluate the efficacy of Upadacitinib in treating CD patients with prior biologic failure.

Methods
A comprehensive literature search was conducted in October 2024 across PubMed, Embase, Cochrane, and ClinicalTrials.gov to identify clinical trials comparing Upadacitinib to placebo in CD patients with prior biologic failure. The inclusion criteria were studies that assessed clinical and endoscopic outcomes in CD patients. A random-effects model meta-analysis was performed using RStudio software to determine the pooled efficacy of Upadacitinib.

Results
Three clinical trials1,2 involving a total of 807 patients were included in the meta-analysis. The analysis revealed that Upadacitinib significantly outperformed placebo in achieving both clinical remission and endoscopic response in this population. Specifically, Upadacitinib was associated with a relative risk (RR) of 2.89 (95% confidence interval [CI]: 2.12–3.95, Figure 1) for clinical remission compared to placebo. Additionally, Upadacitinib demonstrated a significantly higher likelihood of achieving endoscopic response (RR 6.9; 95%CI: 3.36–14.16, Figure 2). These results suggest that Upadacitinib can be a promising treatment option for CD patients who have failed prior biologic therapies.

Conclusion
Upadacitinib is an effective therapeutic option for patients with Crohn’s disease and prior biologic failure, with significant improvements in both clinical remission and endoscopic response compared to placebo.

References
1.Loftus EV, Panés J, Lacerda AP, et al. Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease. The New England Journal of Medicine. 2023;388(21):1966-1980. doi:https://doi.org/10.1056/nejmoa2212728
2.Sandborn WJ, Feagan BG, Loftus EV, et al. Efficacy and Safety of Upadacitinib in a Randomized Trial of Patients With Crohn’s Disease. Gastroenterology. 2020;158(8):2123-2138.e8. doi:https://doi.org/10.1053/j.gastro.2020.01.047

Figure 1

Figure 2
P0497 Faecal Incontinence and Urgency in IBD Patients on Biologic Therapy in Remission: Prevalence and Risk Factors
Authors: Jelakovic M , Peretin L , Kodvanj I , Brinar M , Turk N , Grgic D , Kunovic A , Cukovic-Cavka S , Krznaric Z 
Published: January 2025

Abstract

Background
Despite being in clinical remission, patients with inflammatory bowel disease (IBD) on biologic therapy may experience faecal incontinence (FI) and urgency, significantly impacting their quality of life. This study aimed to determine the prevalence of FI and urgency in this population and to identify associated risk factors.

Methods
A cross-sectional study was conducted in a tertiary referral centre, including IBD patients in remission on biologic therapy (evaluated by partial Mayo score or Harvey-Bradshaw Index). Data on demographic and clinical characteristics were analysed, including age, sex, disease duration, previous biologic therapies, surgical history, and severity indices. FI was defined as a St. Mark’s Vaizey score ≥6, and urgency was assessed using a Visual Analog Scale (VAS) score ≥4. Statistical analysis included chi-squared, Fisher’s exact, and Wilcoxon rank sum tests.

Results
The study included 124 IBD patients (85 Crohn’s disease, 39 ulcerative colitis). FI was observed in 15% of patients, while urgency (VAS ≥4) was reported by 8%. Notably, 14.1% of Crohn’s disease patients in endoscopic remission (SES-CD ≤2) experienced significant FI. Risk factors significantly associated with FI included advanced age (median 49 years vs. 38 years, p=0.007), gender (male 33% vs. female 63%, p=0.014), and history of surgical interventions (58% vs. 26%, p=0.005). Urgency was more prevalent in patients requiring diapers or pads (30% vs. 5.7%, p&lt;0.001) with no other significant factors identified. CRP and faecal calprotectin levels were not significantly associated with either FI or urgency in this cohort.

Conclusion
FI and urgency remain prevalent among IBD patients in clinical but also endoscopical remission on biologic therapy, underscoring the need for continued symptom monitoring and management strategies. Advanced age, gender and surgical history are key risk factors. Future studies should explore targeted interventions to mitigate these complications in this patient group.
P0503 Submucosal hyperechogenicity on intestinal ultrasound is associated with fat deposition and is a predictor of endoscopic non-response to anti-inflammatory treatment in Ulcerative Colitis
Authors: Pruijt M , Neefjes-Borst A , Lange M , de Voogd F , Teichert C , D’Haens G , Gecse K 
Published: January 2025

Abstract

Background
The submucosa is the most responsive wall layer in the monitoring of treatment response in ulcerative colitis (UC) with intestinal ultrasound (IUS).1 However, persistent submucosal thickening, often seen in combination with hyperechogenicity, could be associated with treatment non-response.2 We aimed to understand these transmural changes in UC by correlating IUS findings with histopathology in colectomy specimens.

Methods
In total, 118 patients were included: (cohort 1) 19 UC patients and 52 controls without inflammatory bowel disease who all underwent colectomy, and (cohort 2) 47 UC patients in a prospective longitudinal validation cohort receiving anti-inflammatory treatment. In cohort 1, histopathology slides were scored for inflammation, fat, and collagen deposition in the submucosa by two pathologists, independently, using a semi-quantitative scale (0-3) (Figure 1). For the UC patients in cohort 1, images and histopathology slides of the sigmoid were location matched. IUS parameters were assessed by one sonographer, including relative submucosal echogenicity (RSE), quantified in grayscale units.
In cohort 2, baseline RSE in the sigmoid was compared between endoscopic responders (≥1 point decrease in endoscopic Mayo score [EMS] after 8-26 weeks), and non-responders.

Results
In cohort 1, the indication for colectomy in UC was therapy-refractory disease (16/19, 84%), followed by acute severe colitis (2/19, 11%) and dysplasia (1/19, 5%). In the control groups, indications for surgery included cancer (31/52, 59%), diverticulitis (17/52, 33%), and obstipation (4/52, 8%). No significant differences in fat or collagen deposition in the submuosa were observed within cohort 1. In UC colectomy patients with the presence of submucosal fat deposition (score≥1), the submucosal thickness and RSE were significantly increased on IUS (Table 1). Linear regression showed fat deposition was independently associated with RSE (B=31.27, p&lt;0.001), but fibrosis was not (B=14.89, p=0.097).
In cohort 2, baseline RSE was significantly higher in endoscopic non-responders (n=17) than responders (146.8 vs. 88.7 grayscale units, p=0.003). A cut-off of &gt;108 grayscale units predicted endoscopic non response with 82% sensitivity, 64% specificity, 58% positive predictive value and 86% negative predictive value. This cut-off was associated with an odds ratio of 0.12 (95% CI: 0.03-0.52, p=0.004) for endoscopic response.

Conclusion
In UC, hyperechogenicity of the submucosal layer on IUS is caused by fat deposition. Submucosal hyperechogenicity can be quantified and is a predictor of treatment non-response in UC patients.

References
1.F. de Voogd, Inflamm Bowel Dis 2023. DOI: 10.1093/ibd/izad274.
2.F. de Voogd, Journal of Crohn’s and Colitis 2021. DOI: 10.1093/ecco-jcc/jjab076.535.
P0505 Use of intestinal ultrasound in a tight monitoring approach in Crohn’s disease patients treated with anti-TNFα therapy: a multicentre prospective study
Authors: Palmela C , Revés J , Frias-Gomes C , Morão B , Neto C , Bargas A , Glória L , Cravo M , Dias de Castro F , Cúrdia Gonçalves T , Cotter J , Coelho R , Caldeira A , Torres J 
Published: January 2025

Abstract

Background
Intestinal ultrasound (IUS) is a non-invasive tool increasingly being used to assess response to therapy in Crohn’s disease (CD). Although endoscopic remission (ER) is currently the consensual long-term treatment target, transmural remission is considered a potential target in the STRIDE-II recommendations. We aimed to assess the potential predictive role of ultrasonographic parameters for ER. Additionally, we describe the correlation of IUS with laboratorial and endoscopic parameters.

Methods
This multicentric prospective longitudinal study enrolled adult patients with active CD starting anti-TNF. IUS and ileocolonoscopy were performed at baseline and at 54 weeks. Additionally, IUS was performed at week (W) 14 and 30. The primary outcome was the predictive value of ultrasound remission (normalization of bowel wall thickness (BWT), bowel wall stratification, vascularization and inflammatory fat) for long-term endoscopic remission at 54 weeks (segmental SES-CD=0). The International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) was also calculated and its optimal cut-point to detect ER was identified using ROC analysis. Univariable/multivariable analysis including clinical, biomarkers and ultrasonographic parameters was performed to identify independent predictors of ER.

Results
63 patients with CD were included, of those 57 (90%) were followed-up until week 54. After one year of therapy, 32% achieved ER and 42% IUS remission. Following therapy initiation there was a positive evolution of all IUS parameters. The reduction of BWT and IBUS-SAS was significantly more pronounced in the first 14 weeks of therapy (BWT: W0-14 vs W14-30, p=0.010; IBUS-SAS: W0-14 vs W14-30, p=0.003; W0-14 vs W30-54, p=0.005). Patients with endoscopic response and endoscopic remission had a significantly lower median IBUS-SAS score at all timepoints (Figure 1). The best predictor for endoscopic remission was IBUS-SAS score at W14 (AUC 0.805, cut-off value 52.3). On multivariable analysis, IBUS-SAS at W14 &lt;52.3 was the only independent predictor for ER (OR 7.40; 95% CI 1.20-45.47; p=0.031). Additionally, BWT showed consistent moderate correlation with fecal calprotectin values across all timepoints (ρ=0.44-0.49, p=0.001).

Conclusion
Early assessment of ultrasonographic remission at week 14 can help predict endoscopic remission after 1 year of therapy and offers an opportunity for early therapy optimization. Using a combination of IUS parameters (IBUS-SAS) performed better than BWT alone to predict endoscopic remission. Our results support the use of IUS in a tight monitoring strategy to predict treatment response in CD.

Figure 1: Median BWT and IBUS-SAS score in patients with and without endoscopic response and endoscopic remission. *p&lt;0.05; **p&lt;0.001