bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0848 Engineering and Development of a Novel Bispecific Antibody Targeting both TL1A and α4β7 for the Treatment of IBD
Authors: Ran H , Huang J , Zhang X , Li S , Su C , Chen C , Liu D , Xu X , Chen X , Fei K , Tian L , Peng J , Zhu Z 
Published: January 2025

Abstract

Background
While single-target based therapies for IBD exhibit a significant "therapeutic ceiling," accumulating evidence suggests that multi-target combinatory approaches may provide better efficacy in certain clinical settings. HXN-1002 is a bispecific antibody (bsAb) simultaneously targeting both α4β7 and TL1A, aiming to further enhance clinical efficacy.

Methods
The binding and blocking efficacy of the bsAb for each target were assessed using various in vitro assays, including competitive ELISA and cell adhesion assays for α4β7, and TF-1 apoptosis and DR3-NFκB-Luc reporter assays for TL1A. The synergistic effect of the bsAb was further tested through target internalization and degradation. Subsequently, by using hα4β7/hTL1A transgenic mice, the in vivo efficacy of the bsAb was validated in a DSS-induced colitis model.

Results
HXN-1002 selectively binds to α4β7 but not α4β1, effectively blocking cell adhesion and activation mediated by MAdCAM-1, with activity comparable to Vedolizumab. For TL1A, HXN-1002 binds to both TL1A trimer and monomer with sub-nanomolar affinity, with similar blocking activity to its parental antibody HXN-1001 and RVT-3101. When HXN-1002 simultaneously binds to TL1A and cell surface-expressed α4β7, it significantly enhances internalization of α4β7, led to increased α4β7 degradation and decreased cell surface and total α4β7 expression. In addition, HXN-1002 treatment in the presence of TL1A results in a significantly delayed recovery of α4β7 expression, in comparison to the monospecific Vedolizumab. Studies show that pathological levels of TL1A in patients with various autoimmune disease are sufficient to promote the bsAb-mediated internalization and degradation of α4β7, leading to sustained downregulation of α4β7 expression. In a DSS-induced colitis model using hα4β7/hTL1A transgenic mice, the bsAb exhibited superior therapeutic effects compared to each individual monoclonal antibody.

Conclusion
HXN-1002 is a bsAb that simultaneously blocks the biological functions of α4β7 and TL1A, mediates a significantly enhanced α4β7 internalization and degradation, and is more efficacious than either individual monoclonal antibody or their combinations in both in intro and in vivo models. The bsAb has great potential to significantly enhance efficacy and overcome resistance to Vedolizumab in clinics. Preclinical and IND-enabling studies of the bsAb are currently underway.
P0855 Rise in admissions for Acute Severe Ulcerative Colitis at an Australian tertiary IBD centre with a culturally and linguistically diverse population: Implications for health resource planning
Authors: Bartlett R , Mohamedrashed M , Yogakanthi S , Chew M , Nedumannil L , Pearce R , Lucas S , Chauhan A , Lewis D , Kashkooli S , Garg M 
Published: January 2025

Abstract

Background
Epidemiological data suggests greater risk of inflammatory bowel disease in first- and second-generation migrants from a low to high prevalence country, with risk of ulcerative colitis (UC) preceding Crohn’s disease. Little is known about the effect of this on hospitalisations for UC, including acute severe ulcerative colitis (ASUC). This study evaluated demographic trends of ASUC admissions in a metropolitan healthcare setting with an expanding culturally and linguistically diverse (CALD) population, with admission outcomes compared.

Methods
Demographic and disease characteristics of patients admitted with ASUC at a single tertiary metropolitan centre from January 2016 to October 2024 were recorded. Trends in presentation and outcomes in ASUC patients of European Caucasian and non-European background were compared.

Results
During this 9-year period, 210 patients (88 [41.9%] female, median age 34.5 [16-90] years) had a total of 261 admissions. The ethnicity of patients for UC admissions was 50.9% European Caucasian, 16.2% South Asian, and 13.8% Middle Eastern; ethnicity information was not available for 11% of patients. Of index admissions, 150 (71.4%) met Truelove and Witts criteria for ASUC (62 [41.3%] female, median age 33.5 [16-87] years); 51.3% European Caucasian, 16% South Asian, and 12% Middle Eastern; ethnicity information was not available for 12% of patients. For patients with recorded ethnicity, when comparing all UC admissions in 2016-2019 to 2020-2024, there was a significant increase in the proportion of non-European background patients, increasing from 32.1% to 47.3% (p=0.05), and an increasing trend in ASUC admissions from 29.0% to 46.8% (p=0.08). Median length of stay was 6 days (IQR 5-11) in European Caucasian patients and 6 days (IQR 4-7) in non-European background patients (p=0.11). 12-month steroid dosage was similar in both European Caucasian (median 1685mg) and non-European (median 1612.5mg) patients (p=0.45). 12-month readmission rate was significantly less in the non-European background ASUC population (10.0%) when compared with the European Caucasian population (30.1%), p = 0.02. 7.1% patients of European Caucasian background required inpatient colectomy, compared with 7.5% of non- European background (p=0.94).

Conclusion
There was an increase in proportion of patients of non-European background hospitalised with UC, including ASUC. In ASUC patients, 12 month-steroid usage, colectomy rates, and length of stay of index admission were similar across ethnicities, but patients of non-European background had lower readmission rates. Further studies are required for improved planning of healthcare resources and assessment of ASUC in CALD populations.
P0856 Reasons for switching subcutaneous and oral advanced therapies for IBD: a single-centre experience
Authors: Jackson D , Wilcox S , Hicks L , Dummer S , Evans R , Singh J , Henson S , Thomas L , Shakespeare R , Eadala P , Nagari M 
Published: January 2025

Abstract

Background
The evolution of biologic and small molecule treatments has revolutionised the management of patients with IBD. Yet, a proportion of patients require switching therapy. Switching therapy places high demand on healthcare resource, limits future treatment options and can induce anxiety for patients. The purpose of this study was to explore and quantify the reasons for switching therapy and determine which drugs (and drug classes) were associated with more frequent switches.

Methods
Observational data was obtained from a database of prescriptions for people with IBD who had their therapy switched within Swansea Bay University Health Board. Study period: 30/1/2022 to 20/9/2024 (964 days). Total no. patients 339. Total no. prescriptions 1104 (adalimumab 487; ustekinumab 333; upadacitinib 106; vedolizumab 78; tofacitinib 47; infliximab 44; filgotinib 8; risankinumab 1). Number drug switches 73 (25 male, 48 female; 32 with Ulcerative Colitis, 41 with Crohn’s Disease; average age 39.5 years).

Results
In terms of absolute numbers, the 5 most common reasons for switching were: secondary loss of response, biosimilar switching, primary loss of response, adverse drug reactions and development of antibodies. The 5 most common drug class switches were: Anti-TNF → Anti-TNF (biosimilar switches), Anti-TNF → IL-12/23i, IL-12/23i → JAKi, Anti-TNF → JAKi, JAKi → JAKi. The average no. days on drug was greatest for adalimumab, vedolizumab and ustekinumab respectively.

Conclusion
Secondary loss of response was greatest for adalimumab (9 switches, 1.8% of total ADA prescriptions) and ustekinumab (10 switches, 3.0% of total UST prescriptions). Primary loss of response was greatest for ustekinumab (4 switches, 1.2% of total UST prescriptions) and adalimumab (3 switches, 0.6% of total ADA prescriptions). These data are expected because these drugs are prescribed more frequently, and typically before other therapies are used. We do not routinely check anti-drug antibodies for vedolizumab nor ustekinumab hence only adalimumab was associated with development of antibodies. After biosimilar switches, switching between drug classes was more common than intra-class switches. Of all prescriptions (n=1104), adalimumab was prescribed for the greatest average no. days (1024 days) followed by vedolizumab (693 days) and ustekinumab (599 days). This supports the continued prescription of anti-TNF drugs which constitute a major part of our therapeutic arsenal despite the emergence of novel therapies. Prescribing data can provide insights into the reasons for switching advanced therapies in the treatment of IBD. The longevity of advanced treatments needs to be considered alongside therapy costs when developing drug formularies and treatment pathways.
P0857 The Effectiveness of Ustekinumab in Treating Small Bowel Crohn’s Disease Assessed by Magnetic Resonance Enterology
Authors: Wang Y , Nie J , Ren Y , Mao R 
Published: January 2025

Abstract

Background
Crohn’s disease (CD) is a chronic relapsing and remitting inflammatory disease that affects the whole gastrointestinal tract. Approximately two-third of the CD patients have ileitis (with or without colitis) at the time of diagnosis. There is increasing evidence suggests that small bowel Crohn’s disease (SBCD) is distinct from colonic CD in several aspects, such as genetic risk factors, clinical course and treatment response. This study aims to explore the effect of UST for SBCD and compared the treatment response in different segments of small intestine.

Methods
This is a retrospective observational cohort study conducted at the First Affiliated Hospital, Sun Yat-Sen University. Patients with CD receiving UST were consecutively recruited from May 2021 to June 2023. MRE assessment was performed at baseline and weeks 26, and the MaRIA score was calculated. Demographic features and clinical characteristics of patients at baseline and weeks 26 (±3 weeks) were recorded. The primary endpoint of this study was healing of severe inflammation detected by MRE at weeks 26. Improvement in inflammation assessed by MRE is defined as the difference in the Maria score, calculated by subtracting the Maria score at week 26 from the score at week 0. Define ΔMaria baseline (difference in ratings divided by week 0 ratings)greater than 50% as inflammation improvement and less than 50% as no inflammation improvement. The second endpoint was the proportion of patients achieving clinical remission (CDAI score 150 at weeks 26) and the proportion of patients reaching clinical response (the reduction of CDAI 100 points when compared with baseline).

Results
A total of 136 CD patients were included for this study. At 26 weeks, the inflammatory status in the ileum (p&lt;0.001) and terminal ileum(p&lt;0.001) showed significant improvement compared to the jejunum (Figure 1A). When accounting for baseline intestinal inflammatory status, the “relative baseline MRE inflammation change” still exhibited the same trend at 26 weeks (p&lt;0.001) (Figure 1B). However, no statistically significant differences were observed between the ileum and terminal ileum, upper jejunum and lower jejunum. In terms of secondary outcomes, 33 patients were excluded because of missing values of CDAI. Of 103 patients included for analysis, clinical response and remission were achieved in 75 (72.8%) and 78 (75.7%) patients separately (Figure 1C).

Conclusion
We conducted this observational study and found that ileum location was more likely to achieve MRE response and remission than jejunum, even though there was no difference between ileum and terminal ileum.
P0858 Rate of participation in a second randomized clinical trial and factors associated with the likelihood of participation among inflammatory bowel disease patients who already experienced a randomized clinical trial
Authors: Gabbiadini R , Pitoni D , Bertoli P , Privitera G , Dal Buono A , Danieli P , Bezzio C , Armuzzi A 
Published: January 2025

Abstract

Background
The development of new therapies in inflammatory bowel disease (IBD) has become increasingly difficult, partly due to challenges in recruiting patients for clinical trials. In the last 20 years, the average recruitment for IBD-trials has decreased to approximately 0.1 patients per site per month. The aim of our study is to assess the rate of participation in a second trial in IBD patients who already experienced a clinical trial and to investigate factors that are associated with a patient’s likelihood of participating in a second clinical trial.

Methods
This is a single-center, retrospective study. We included IBD patients who participated in at least one for-profit randomised clinical trial at the IBD centre of IRCCS Humanitas Research Hospital (Milan, Italy) between 2015 and 2024.

Results
293 patients were included. Baseline demographic and clinical characteristics are shown in Table 1. After the end of the 1° trial, patients were followed for a median of 30 months (range 1-169). During the follow-up, 85 (29.0%) participated in a second trial. In the multivariate analysis, a distance from home to the IBD clinic &gt; 100 km (OR 0.556, 95% CI 0.326-0.983, p=0.043) and being in clinical remission at the end of the first trial (OR 0.567, 95% CI 0.324-0.991, p=0.046) were significantly associated with a lower likelihood of participating in the second trial.

Conclusion
Approximately one third of patients participated again in a second clinical trial. Long distance from the IBD clinic and remission at the end of the first trail reduce the probability of participation in the second trial. Understanding the factors that hinder or promote participation in IBD clinical trials is crucial for enhancing patient involvement in research.
P0859 Handgrip Strength and Physical Activity in Children with IBD: Insights into Sarcopenia Risk
Authors: Kasznár E , Karoliny A , Gombos E , Szentannay J , Szabó A , Dohos D , Bajzat D , Timár Á E , Müller K 
Published: January 2025

Abstract

Background
Approximately 15-20% of patients with inflammatory bowel disease (IBD) are diagnosed in childhood. Sarcopenia is known to be a poor prognostic factor, contributing to prolonged hospital stays, increased surgical complications, and reduced medication efficacy. While about one-third of adult IBD patients are affected by sarcopenia, data on its prevalence and impact in pediatric IBD are limited. Our aim was to assess and compare the physical activity and handgrip strength of healthy children and paediatric patients with IBD.

Methods
Single-centre, non-interventional case-control study. Anthropometric data, sex and age of healthy and sick children were recorded. Hand grip strength and physical activity were assessed using the JAMAR hydraulic hand dynamometer and PAQ-C questionnaire. Based on handgrip strength, the risk of sarcopenia was categorized into three groups using the Hungarian NETFIT database: ‘high risk’ (significant development needed), ‘some risk’ (improvement needed), and ‘healthy’.

Results
We analyzed data from 75 children with IBD (33 with Crohn’s disease, 40 with ulcerative colitis, and 2 with IBD-U) and 75 healthy controls. Girls comprised 42.5% of the cohort. The mean age was 15.5 ± 1.9 years in both groups. Most IBD patients (82.7%) were in remission, with a BMI z-score of 0.17 ± 1.6 kg/m² compared to -0.16 ± 0.8 kg/m² in healthy controls. Based on handgrip strength, 24% of IBD patients were at ‘some risk’ and 39% at ‘high risk’ for sarcopenia, while none of the healthy children were in the ‘high risk’ group and 33% were in the ‘some risk’ group. Physical activity (PAQ-C score) was significantly higher in healthy children compared to those with IBD (2.4 ± 0.61 vs. 2.1 ± 0.6, p &lt; 0.05).

Conclusion
Compared to healthy peers, children with IBD exhibit a higher prevalence of muscle strength requiring improvement and lower physical activity levels, even though the majority were in remission. Our findings highlight the importance of assessing physical activity and sarcopenia in children with IBD.
P0863 Risk of colitis in patients with Inflammatory Bowel Disease exposed to checkpoint inhibitors – a national Danish cohort study
Authors: Dahl E , Christensen K R , Jacobsen H A , Anders K , Dige A , Svane I M , Donia M , Bjerrum J T , Seidelin J B 
Published: January 2025

Abstract

Background
Patients with intestinal inflammatory diseases such as ulcerative colitis (UC), Crohn’s disease (CD) and microscopic colitis (MC) are excluded from clinical trials with immune checkpoint inhibitors (ICI) due to assumed increased risk of activation of the underlying immune mediated disease. Therefore, we aimed to evaluate the risk of developing disease activity or checkpoint inhibitor immune-mediated enterocolitis (IMEC) in patients with UC, CD or MC treated with ICI in a real-world cohort.

Methods
We performed a nation-wide Danish retrospective cohort study on patients with UC, CD and MC with cancer treated with checkpoint inhibitors from 2010 to 2024.

Results
Eighty-five patients were included in the study and IMEC was observed in 39 (46%) cases. IMEC was not severe in fifteen cases, and it was possible to continue ICI treatment in 61 patients (72%). When compared to a control cohort without intestinal disease (n=138), patients with UC, CD, and MC had a higher risk of IMEC if treated with anti-PD-1 or anti-PD-L1, hazard ratio (HR) 4.93, p&lt;0.001. Not enough patients were treated with CTLA-4 alone or in combination with anti-PD-1/PD-L1 treatment to calculate these groups and therefore we can only describe the risk in patients treated with anti-PD-1/PD-L1. Multivariate logistic analysis showed that patients with CD had a lower odds ratio (OR) of IMEC compared to patients with UC and MC (OR 0.07, p=0.02).

Conclusion
Patients with CD appear to have a lower risk of IMEC compared to patients with UC and MC. Despite the high risk of developing IMEC in patients with UC, CD, and MC, 72% of the patients were able to continue first-line treatment with ICI after managing IMEC.
P0866 Upadacitinib improves symptomatic, biochemical, and intestinal ultrasound parameters in active UC patients up to one year after treatment induction – one year interim results from the IBD-DACH study EUROPE
Authors: Zeissig S , Schmelz R , Helwig U , Moschen A R , Greuter T , Fischer I , Hammer L , Rath S , Kucharzik T , Maaser C 
Published: January 2025

Abstract

Background
Upadacitinib (UPA), a reversible and selective Janus kinase-inhibitor was approved for the treatment of moderate-severe ulcerative colitis (UC) in 2022 (1). Despite substantial evidence from pivotal trials, multinational, prospective real-world (RW) data remains limited. We report symptomatic, biochemical, and intestinal ultrasound (IUS) data after one year of UPA therapy in a large, multinational RW UC cohort.

Methods
EUROPE is an ongoing, prospective, non-interventional, multi-country study in active UC patients who initiate UPA therapy. Primary study aim is to assess RW effectiveness and the predictive value of early (IUS) response for outcomes at week 52 (W52). Here, we show symptomatic, biochemical, and IUS results (bowel wall thickness, BWT) at baseline (BL), W8 and W52 of 111 UC patients. Safety data was available for 263 patients ((≥ 1 dose of UPA).

Results
Here, 111 UC patients (59.5% male, median age 37.6 (28.0 - 49.6) yrs, median disease duration 6.95 (2.36 – 12.65) yrs) with a visit at W52 were included. Of these, 50.5% (n = 56) had pancolitis and 88.3% (n = 98) were advanced therapy experienced. Of note, 39.8% (n = 39) of the latter had been exposed to ≥ 3 biologicals. Patients had signs of active inflammation at BL (median FCal: 727 (263 – 1500) µg/g, median CRP: 6.45 (1.3 – 20.5) mg/L) with BL steroid use in 46.8% of patients (n = 52).
At W8 after UPA induction, the rate of patients in symptomatic remission significantly increased from 19.8% (n = 22) at BL to 69.4% (n = 77) at 8W and to 67.6% (n = 75) at W52 (both p &lt; 0.001 vs. BL, fig.1). Fecal calprotectin and CRP decreased until W8 and remained low until W52 (table 1). BWT in the sigmoid colon decreased from median 5 (3.9-6) mm at BL to 3 (2 – 4) mm at W8 and to 2.85 (2 – 3.6) mm at W52. Of note, patients with a BWT ≤ 3mm at W8 demonstrated higher rates of symptomatic remission at W52 vs those with BWT &gt; 3mm (62.0% vs. 38.0%). In 263 patients, 52.9% adverse events were detected (139 events, 60 patients) of which most were non-serious (SAEs: 8.4% (n = 22). One acute myocardial infarction and 8 thromboembolic events were detected (in 6 patients, one event was a pulmonary embolism.

Conclusion
In this one-year interim analysis of the EUROPE study, UPA treatment in UC was associated with a positive benefit/risk profile including clinical, biochemical, and IUS improvements. Patients achieving BWT normalisation at 8W were more likely to be in symptomatic remission after one year compared to those without BWT normalisation.

References
1. Current SmPC Upadacitinib
P0870 Efficacy and Safety of Different Doses of Adalimumab in Crohn's Disease: A Multicenter Cohort Study in Infliximab-Naïve and Infliximab-Exposed Patients
Authors: Xu Z , Peng X , Zhi M , Zhang M 
Published: January 2025

Abstract

Background
High adalimumab dosing for Crohn's disease remains uncertain. This study evaluated the efficacy and safety of different adalimumab doses in infliximab-naïve and -exposed patients to guide individualized therapy.

Methods
A retrospective, multicenter cohort study with propensity score weighting included Crohn’s disease patients treated at Sun Yat-sen University Sixth Affiliated Hospital from January 2019 to July 2022. Clinical remission, objective response, and sustained remission rates were assessed at 12 and 52 weeks.

Results
Of 223 patients (165 standard-dose, 58 high-dose), propensity score–adjusted analysis showed no difference in clinical remission at Week 12 between high- and standard-dose groups (80.2% vs. 79.8%, P = 0.952). Infliximab exposure affected outcomes, with higher remission in the high-dose group among previously exposed patients (74.6% vs. 39.1%, P = 0.013). By Week 52, clinical remission was similar (65.2% vs. 50.8%, P = 0.099), though objective response was superior in the high-dose group for infliximab-exposed patients (71.9% vs. 25.2%, P = 0.002). In TNF-naïve patients, high-dose adalimumab increased Week 12 response (94.3% vs. 78.7%, P = 0.039) and Week 52 objective remission (48.1% vs. 30.0%, P = 0.037). Safety profiles were comparable, with similar adverse event rates (58.6% vs. 56.4%, P = 0.878).

Conclusion
High-dose adalimumab offers therapeutic benefits for infliximab-exposed patients in short- and long-term phases, an effect not observed in infliximab-naïve patients, with comparable safety to standard dosing.