bluuebunny/crossref_metadata_2025 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

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

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

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

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<0.001) and terminal ileum(p<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<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

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 > 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

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 < 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

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<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

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 < 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 > 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

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.
P0872 Corticosteroid sparing effects of treatment with guselkumab in patients with moderately to severely active Crohn’s disease: Phase 3 GRAVITI study results through week 48
Authors: Hart A , Panaccione R , Steinwurz F , Cao Q , Hisamatsu T , Nancey S , Olurinde M , Yang Z , Merrall E , Terry N A , Sands B E
Published: January 2025

Background

The Phase 3 double-blind, placebo-controlled, treat-through GRAVITI study evaluated the efficacy and safety of subcutaneous (SC) induction and maintenance treatment with guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor that binds to IL-23 and CD64 (a receptor on cells that produce IL-23), in participants (pts) with Crohn’s disease (CD). Here we report the corticosteroid (CS)-sparing effects of treatment with GUS vs placebo (PBO) through Week (Wk) 48.

Methods

This study randomized pts 1:1:1 to GUS 400mg SC every 4 wks (q4w)→200mg SC q4w, GUS 400mg SC q4w→100mg SC q8w, or PBO. PBO pts who met rescue criteria were eligible for rescue treatment with GUS at Wk16. For pts receiving oral CS at baseline, doses were maintained through Wk12. Mandatory oral CS tapering began at Wk12 unless medically not feasible. CS use, CS-free clinical remission, and 90-day CS-free clinical remission at Wk48 were assessed.

Results

The full analysis set included 347 pts, mean (SD) age, 37.5 (12.89) yrs; mean CD duration, 8.0 (8.05) yrs; mean (SD) CDAI score, 296.9 (52.68); and mean (SD) SES-CD score, 12.0 (6.94). No pts were receiving beclomethasone at baseline. Among all pts receiving oral CS (prednisone or budesonide) at baseline (103/347; 29.7%), greater proportions of GUS-treated pts (100mg SC q8w: 62.5%, adjusted treatment difference ∆41.7%; 200mg SC q4w: 81.6%, ∆62.9%) were not receiving CS at Wk48 vs PBO (18.2%). Also, among pts receiving oral CS at baseline, greater proportions of GUS-treated pts (100mg SC q8w: 59.4%, ∆38.8%; 200mg SC q4w: 81.6%, ∆62.9%) were not receiving CS for at least 90 days prior to Wk48 vs PBO (18.2%) (Table 1).

Significantly greater proportions of GUS-treated pts (100mg SC q8w: 60.0%, ∆42.8%; 200mg SC q4w: 66.1%, ∆48.9%) achieved clinical remission at Wk48 vs PBO (17.1%) (Figure 1). Likewise, greater proportions of GUS-treated pts (100mg SC q8w: 59.1%, ∆42.8%; 200mg SC q4w: 66.1%, ∆49.8%) achieved CS-free clinical remission at Wk48 vs PBO (16.2%). Similarly, greater proportions of GUS-treated pts (100mg SC q8w: 58.3%, ∆41.9%; 200mg SC q4w: 65.2%, ∆49.0%) achieved 90-day CS-free clinical remission at Wk48 vs PBO (16.2%).

Conclusion

In pts with moderately to severely active CD, greater proportions of GUS-treated pts achieved CS-free efficacy outcomes through Wk48 vs PBO.
P0873 Risk factors for difficult endoscopic bowel dilatation of strictures among patients with inflammatory bowel disease (IBD): Findings from a IBD tertiary centers in Poland and Czech Republic
Authors: Lewandowski M.D. K , Lukas M , Kaniewska M , Tulewicz-Marti E , Karłowicz K , Bednarczuk A , Kolar M , Jirsa J , Lukas M , Rydzewska G
Published: January 2025

Background

Intestinal strictures are a common and serious complication of inflammatory bowel disease (IBD). Endoscopic balloon dilatation (EBD) is the first step treatment to avoid the surgery.

Methods

The aim of this study was to assess the prevalence, risk factors and clinical sequelae of difficult EBD. In this retrospective, multi-center study, 861 IBD patients treated with EBD due to strictures were included. We evaluated the risk factors for difficult EBD, defined as a ≥3 per year.

Results

During 23.00 (14.00;42.00) months of median follow-up there were 392 (45.5%) easier EBD performed, while difficult EBD were done in 489 (54.5%) cases. Long term efficacy of EBD, defined as a >12 months without surgery was achieved in 392 (100%) easier vs in 457 (97.4%) difficult EBD, V = 0.11, P = 0.004. However, 149 (17.3%) patients underwent surgery due to unsuccessful EBD. The most important risk factors for difficult EBD, classified as modifiable, were smoking and treatment with adalimumab (especially if through level was normal) and ustekinumab. While vedolizumab (VDZ) and immunosuppressive therapy was identified as a protective factor. The multivariable logistic regression indicated good fit of the model to the data, pointing to protective role of total parental nutrition (TPN) and worsening of smoking (for both P < 0.001).

Conclusion

In this study, we observed a high incidence of difficult endoscopic balloon dilations present in 54.5% of cases. Treatment with adalimumab and ustekinumab, was a risk factor for more difficult endoscopic procedures, while the use of vedolizumab and total parental nutrition seems to have a protective effect. There has been an increasing number of difficult endoscopic procedures. Lower efficacy of these procedures leads to an increased frequency of complications, need for surgery, and the ever-increasing healthcare cost. Evaluating transmural healing during biological treatment using non-invasive techniques should therefore be identified as crucial factor. However, only prospective studies evaluating the effectiveness of such management in terms of accelerating the process of transmural healing and modifying the course of the disease in order to minimize the formation of strictures will ultimately guide new standards of care.
P0876 One-year effectiveness and safety of ustekinumab treatment in patients with ulcerative colitis: An Asan-Crohn’s and Colitis Association in Daegu-Gyeongbuk (CCAiD) multicentre real-world cohort study
Authors: Baek J E , Kim M K , Kim E S , Kim K O , Jo H H , Hwang S W , Park S H , Jang B I , Kim E Y , Yang S K , Kim S K , Ye B D
Published: January 2025

Background

The real-life data on ustekinumab (UST) for Asian patients with ulcerative colitis (UC) are limited. We aimed to assess one-year effectiveness and safety of UST for Korean patients with UC.

Methods

This was a multicentre retrospective study on patients with UC who received UST at 4 academic centers in Korea between January 2021 and October 2023. The primary endpoint was clinical remission defined as partial Mayo score (PMS) ≤2 and no subscore >1 at week (W) 8 of therapy. Secondary endpoints included clinical remission (W16–20 and W52–56), corticosteroid-free clinical remission (W8, W16–20, and W52–56), clinical response (W8, W16–20, and W52–56), endoscopic remission defined as Mayo endoscopic subscore (MES) 0–1 (W16–20 and W52–56), interval shortening and durability of UST therapy till W52–56, and adverse events.

Results

A total of 60 patients (Male, 63.3%; Median age, 44.5 years; Disease duration, 6.5 years; Previous exposure to advanced therapies, 70.0%; Extensive colitis, 65.0%; Median baseline Mayo score, 8; Concomitant use of immunomodulators, 40.0%) were included. Excluding one patient in clinical remission at baseline, 49.2% (29/59) achieved clinical remission at W8. At W16–20, and W52–56, 59.3% (35/59), and 55.9% (33/59) achieved clinical remission. The clinical response rates at W8, W16–20, and W52–56 were 67.9% (40/59), 69.5% (41/59), and 66.1% (39/59), respectively (Figure 1). Endoscopic remission rates at W16–20 and W52–56 were 55.9% (33/59) and 37.3% (22/59), respectively (Figure 1). Multivariable analysis identified factors associated with clinical remission at W52–56 (body mass index, adjusted odds ratio [aOR]: 1.26, 95% confidence interval [CI] 1.00–1.57, p<0.05; previous exposure to advanced therapies, aOR: 0.20, 95% CI 0.04–0.98, p<0.05; concomitant use of immunomodulators, aOR: 4.69, 95% CI 1.04–21.06, p=0.04; endoscopic remission at W16–20, aOR: 13.47 95% CI 2.87–63.30, p<0.01). Till W52–56, the interval shortening rate for subcutaneous UST treatment from every 12 to 8 weeks was 20% (12/60). Nine patients (15.0%) stopped UST, primarily due to a secondary loss of response (8.3%, 5/60), followed by a primary non-response (6.7%, 4/60). Adverse events occurred in 24 patients (40.0%) and serious adverse event in one patient (1.7%) (Table 1).

Conclusion

UST was effective with an acceptable safety profile for Korean patients with UC. Previous exposure to advanced therapies was associated with a lower probability of clinical remission at one year after UST therapy.

Financial support

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2021R1A2C2095096).
P0880 Sphingosine 1-phosphate (S1P) Receptor Modulators for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Campedelli L , Antunes V , Perim V , Marinho A , Junkes Milioli N
Published: January 2025

Background

Ulcerative colitis (UC) is a chronic autoimmune inflammatory disease of the colon, classified as mild, moderate, or severe. Conventional treatments, including corticosteroids and thiopurines, are effective for mild to moderate disease, while biologics and small molecules are used for more severe cases. Previous studies have shown the benefits of Sphingosine-1-phosphate (S1P) receptor modulators in UC, but their efficacy in specific patient subgroups remains unclear. This meta-analysis aims to evaluate the efficacy of S1P receptor modulators in achieving clinical remission in UC patients, focusing on prior treatment history, including corticosteroid and TNF-alpha inhibitor use.

Methods

We searched PubMed, Embase, Cochrane, and ClinicalTrials.gov in August 2024 for clinical trials assessing the efficacy of S1P receptor modulators in UC patients, comparing them to placebo. A random-effects model was used for this meta-analysis and RStudio software was used for statistical analysis.

Results

Four clinical trials were included1,2,3, comprising 1,670 patients with UC. Two studies evaluated ozanimod, and three evaluated etrasimod. Compared to placebo, S1P inhibitors were effective in achieving clinical remission in patients with corticosteroid (CS) use at baseline (RD 0.1; 95% CI 0.04-0.17; Figure 1A), in those without CS use at baseline (RD 0.21; 95% CI 0.11-0.31; Figure 1B), and in those with no prior TNF-alpha inhibitor use (RD 0.19; 95% CI 0.12-0.26; Figure 2B). Data for patients with prior TNF-alpha inhibitor use were available in only two trials, showing a trend toward efficacy (RD 0.07; 95% CI -0.00 to 0.13; Figure 2A), but statistical significance was not reached.

Conclusion

S1P receptor modulators are effective in achieving clinical remission in UC patients, including those without prior TNF-alpha inhibitor use, as well as in patients with or without corticosteroid use at baseline.

References

1.Sandborn WJ, Vermeire S, Peyrin-Biroulet L, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies. The Lancet. 2023;0(0). doi:https://doi.org/10.1016/S0140-6736(23)00061-2

2.Sandborn WJ, Feagan BG, Wolf DC, et al. Ozanimod Induction and Maintenance Treatment for Ulcerative Colitis. New England Journal of Medicine. 2016;374(18):1754-1762. doi:https://doi.org/10.1056/nejmoa1513248

3.Sandborn WJ, Feagan BG, D’Haens G, et al. Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis. New England Journal of Medicine. 2021;385(14):1280-1291. doi:https://doi.org/10.1056/nejmoa2033617

Figure 1

Figure 2
P0885 Therapeutic Concepts for Pyoderma Gangrenosum as an Extraintestinal Manifestation in Chronic Inflammatory Bowel Diseases
Authors: Guse J , Rüddel J , Teich N , Stallmach A , Lange K
Published: January 2025

Background

Extraintestinal manifestations (EIM) are common complications of inflammatory bowel disease (IBD), occurring in 6–48% of patients. Among these, pyoderma gangrenosum (PG) is relatively rare but challenging to treat due to its potentially aggressive course. This condition poses a significant therapeutic challenge. This retrospective analysis aims to characterize affected patients and evaluate the efficacy of various therapeutic approaches on both IBD activity and PG healing, with the goal of identifying optimal treatment strategies, particularly for patients with multiple prior therapies.

Methods

In a retrospective multicenter study, patients with IBD and PG were analyzed. Demographic data, prior medications, surgeries, and disease-specific factors were considered to assess different treatment strategies.

Results

The cohort included 22 patients (median age: 47 years; 73% were women). Crohn’s disease was present in 77% of cases, while 23% had ulcerative colitis. More than half of the patients (59%) had undergone surgery, 85% of whom had an intestinal stoma. 50% of patients had received prior biologic therapy, with 82% treated using anti-TNF agents. PG most commonly affected the lower extremities (55%) or peristomal areas (41%). 17 patients received anti-TNF therapy (mostly infliximab as first- or second-line treatment), which resulted in complete healing in 88% of cases. Systemic steroid therapy (prednisolone) was used in 11 patients (50%), leading to partial improvement in less than 20%. Tacrolimus was administered to 8 patients, with a response rate of 63% and complete healing in 50%. One non-responder to tacrolimus successfully switched to infliximab. All patients responded to at least one anti-TNF agent, while tacrolimus failed as a first-line therapy in 75% of cases. One patient received a JAK inhibitor but did not achieve PG healing. Among those with complete PG healing, 15 patients (79%) were also in clinical remission. The median time to achieve complete healing of PG was five months. Complete healing of PG was achieved in 19 patients (86%).

Conclusion

These findings demonstrate that anti-TNF therapy is an effective treatment strategy for patients with IBD and pyoderma gangrenosum, proving successful as a first- or second-line treatment. Switching between anti-TNF agents was beneficial in cases of initial treatment failure. Systemic steroids showed limited success and Tacrolimus showed some efficacy. Both were inferior to anti-TNF therapy, especially as a first-line option. Complete healing of PG correlates with clinical remission of IBD and may take several months, a consideration important for treatment selection and evaluation. In summary, anti-TNF agents should be the primary therapeutic option for PG in IBD patients.
P0887 Through the lens of inflammatory bowel disease: Impact of rheumatological involvement on disease course
Authors: Khemiri W , Ayari M , Bettaieb H , Boudokhane M , Ben Azzouz S , Douggui M H , Jomni T
Published: January 2025

Background

Inflammatory bowel diseases (IBD) are systemic disorders that may be associated with extraintestinal manifestations in up to 40% of patients. Recognizing the recurrent emergence of these manifestations in IBD, with a particular emphasis on rheumatological aspect, becomes a pivotal focal point for a holistic therapeutic approach. The aim of this study was to evaluate the impact of ankylosing spondylitis in IBD on disease course

Methods

We conducted a retrospective and comparative study, including patients followed for IBD over an 8-year period [2014 - 2022]. Clinico-biological data, disease severity, and long-term outcomes (surgery and disease course) were collected. IBD patients with ankylosing spondylitis (group1) and patients without (group2) were compared.

Results

One-hundred IBD patients were enrolled with a sex ratio of M/F=2.44 and a mean age of disease diagnose of 37.26±13.46 years. Eighteen patients had ankylosing spondylitis (18%). The two groups were comparable in terms of age at disease onset, gender, smoking status and family history of IBD (p=0.65; p=0.9, p=1 and 0.1 respectively). In Crohn's disease, there was no difference between the two groups regarding the extent of the disease (p=0.71), the presence of upper gastro-intestinal tract involvement (p=0.11) and perineal manifestations (p=0.7). Inflammatory, structuring, and penetrating phenotypes were also comparable between the two groups (p=0.67; p=0.3; p=1 respectively). However, the occurrence of acute intestinal obstruction was significantly more common in ankylosing spondylitis patients (G1:54% vs. G2:10%; p=0.004). As for ulcerative colitis, extensive presentation and the occurrence of disease extension during follow-up was comparable between the two groups (p=0.78 and p=0.66). None of the patients with or without rheumatological involvement had any dermatological or ophthalmological involvement related to IBD, but there was a more significant prevalence of hepatic manifestations in ankylosing spondylitis group (G1:16% vs. G2:2%, p=0.01). The mean number of flare-ups was not significantly different between the two groups (G1:3.21±1.47 vs. G2:2.53±1.4; p=0.06). Regarding treatment, recourse to methotrexate (G1:16% vs. G2:2%; p=0.01) and the use of anti-TNF agents (G1:77% vs. G2:22%; p<0.001) was more frequent in group 1, with no difference in the occurrence of adverse events (p=1), the use of corticosteroids (p=0.22) or azathioprine (p=0.1). Surgical treatment was more frequently indicated in ankylosing spondylitis patients (G1:51% vs. G2:30%; p=0.06) with comparable post-operative relapse of Crohn's disease (p=1).

Conclusion

In our study, rheumatological involvement was not likely responsible of a more severe clinical phenotype of IBD.
P0893 Angiopoietin-like Protein 8 (ANGPTL8) in Inflammatory Bowel Disease and Its Response to Anti-TNFα Therapy; A Prospective Multi Center Study
Authors: Shehab M , Al-Fajri S , Alborom M , Alrashed F , Alshammaa F , Alfadhli A , Devarajan S , Abu-Farha M , Alkhairi I , Cherian P , Al-Mulla F , Abubaker J
Published: January 2025

Background

Crohn’s disease (CD) is a chronic condition characterized by persistent inflammation of the gastrointestinal tract. Tumour necrosis factor-alpha (TNFα), a key pro-inflammatory cytokine, plays a crucial role in the disease process. Anti-TNF therapies have significantly improved CD treatment by reducing inflammation. Emerging evidence show that Angiopoietin-like protein 8 (ANGPTL8) is a novel protein and may also be involved in regulating inflammation. This study aimed to investigate the changes in ANGPTL8 level in patients with IBD compared to healthy individuals and evaluates the impact of Anti-TNF therapies on this protein.

Methods

This is a prospective multi-center observational study. Patients were recruited from January 2022 to June 2024. Patients were divided into 3 groups; patients with CD in clinical remission receiving infliximab for at least 24 weeks (IFX-experienced group), healthy controls (control group), and patients with CD scheduled to start infliximab (IFX-naïve group). ANGPTL8 levels were measured 24 hours before next maintenance infliximab dose in IFX-experienced group, randomly in control group, and at week 0 and week 24 in IFX-naïve group. ANGPTL8 levels were measured using enzyme-linked immunosorbent assays (ELISA). A normality test was conducted for continuous variables, accordingly variables with normal distribution a parametric t-test was applied, otherwise Mann–Whitney U test was applied to compare between treated and untreated groups for skewed variables.

Results

A total of 166 patients were included in this study. The number of patients with CD and IFX-experienced and IFX-naive were 82 and 13, respectively. Seventy-one were healthy controls. Mean age ranged from 27 to 33 years of age across the three groups (table 1). Eighty-four (51%) were females. ANGPTL8 levels were significantly higher in patients with CD (138.26 ± 8.47 pmol) compared to the healthy control group (102.52 ± 5.99 pmol, p = 0.001). Among the 13 IFX-naive patients receiving anti-TNFα treatment, ANGPTL8 levels decreased significantly from 145.06 ± 17.93 pmol pre-treatment (week 0) to 81.78 ± 10.61 pmol post-treatment (week 24), p = 0.007.

Conclusion

Our findings suggest that ANGPTL8 is elevated in CD and may be involved in the inflammatory processes. The marked reduction in ANGPTL8 levels following anti-TNFα treatment indicates its potential as a biomarker for treatment response. Further research is needed to understand the exact mechanisms through which ANGPTL8 influences CD progression and its utility in clinical practice.
P0908 Prognostic Nomogram Incorporating Limberg Score for Predicting Bowel Surgery in Patients with Ulcerative Colitis
Authors: Li M ,   Chuhan Zhang# Pingxin Zhang Ren Mao Shihui Li Yujun Chen Xiaoyan Xie Minhu Chen Yun Qiu
Published: January 2025

Background

This study aimed to assess the role of intestinal ultrasound (IUS) in monitoring and predicting long-term bowel surgery in patients with ulcerative colitis (UC).

Methods

This retrospective study analyzed documented IUS examinations of UC patients from a prospective inflammatory bowel disease registry. A nomogram was constructed to predict bowel surgery based on factors identified by both multivariate Cox and logistic regression model. Model performance was assessed using receiver-operating characteristic (ROC) curves and decision curve analysis (DCA).

Results

A total of 171 patients were enrolled. Significant correlations were observed between IUS parameters and disease activity as assessed by colonoscopy, as well as with other inflammatory indices. During a median follow-up of 32 months, 12 patients (7.02%) underwent UC-related bowel surgery. Factors associated with bowel surgery identified by the Cox regression included the Limberg score (OR 3.86, 95% CI 0.98−15.26, p=0.054), steroids use (OR 7.31, 95% CI 0.85−62.51, p=0.069), perianal lesions (OR 37.19, 95% CI 1.94−712.34, p=0.016), and age at diagnosis (OR 1.08, 95%CI 1.02−1.13, p=0.007). A nomogram incorporating these factors was established. Both ROC curve and DCA analysis indicated that the nomogram, which included the Limberg score, had an area under the curve (AUC) of 0.872 and a C-Index of 0.875. The nomogram based on logistic regression analysis also showed good performance.

Conclusion

We developed and validated a prognostic nomogram incorporating the Limberg score to identify patients with UC most likely to require bowel surgery. This nomogram can improve risk stratification and aid personalized therapeutic decisions for UC patients.
P0912 Factors associated with adherence to the Mediterranean diet in patients with Ulcerative Colitis after pouch surgery
Authors: Elial-Fatal S , Pfeffer-Gik T , Shelly S , Pauker M H , Friedenberg A , Cohen S , Barkan R , Ollech J , Yanai H , Wasserberg N , White I , Dotan I , Godny L
Published: January 2025

Background

Dietary interventions are increasingly used in managing inflammatory bowel diseases (IBD). Effectiveness often depends on patient adherence. We aimed to assess the nutritional and clinical feasibility of a Mediterranean diet (MED) based nutritional education program (IBDMED) in patients with ulcerative colitis (UC) after pouch surgery.

Methods

Patients who underwent pouch surgery due to ulcerative colitis and who were clinically inactive were randomly assigned to either (A) Intervention group – IBDMED program including MED based dietary counseling and weekly phone calls with study dietitian, access to an application with dietary information, recipes, online chat and fitness trackers, or (B) Standard of care dietary counseling for 8 weeks. Patient adherence was assessed using a predefined IBDMED score during the intervention and at 1-year follow-up (NCT04082559)

Results

A total of 32 patients after pouch surgery (median age- 50 (35.7-64.7) years, median BMI- 24.9 (22.7-29.1) Kg/m2, female gender 40.6%) underwent an 8-week nutritional intervention (group A: n=18, group B: n=14). Highest satisfaction score (5/5) was rated in both groups (88.9% vs. 71.5%, p=0.21). Reduction in number of bowel movements was comparable across groups (22.2% vs. 14.3%, p=0.57), with a trend towards a greater improvement in stool consistency in the intervention group (44.4% vs. 14.3%, p=0.07). The magnitude of dietary change was higher in the intervention group with 66.6% reported significant changes in their dietary habits vs. 21.4% in the control group (p=0.01). Increased consumption of the IBDMED recommended food components was reported to be significantly higher in the intervention group for vegetables, olive oil and yogurt (p<0.05 for all, Figure 1). Notably, effect on lifestyle behaviors of patients’ family members was reported in 44.4% in the intervention group vs. 21.4% in the control group (p=0.17). Factors contributing to increase adherence to the intervention were weekly phone calls with the dietitians (100%), followed by the IBDMED daily questionnaire and fitness trackers (both 83.3%), online chat with the dietitians (50%), weekly progression reports (33.3%) and online recipes (22.2%). Finally, IBDMED adherence score at 1-year follow-up tended to be higher in the IBDMED group (11.7 + 2.1 vs. 9.8 + 2.4, p=0.07, n=22).

Conclusion

The IBDMED program is feasible and effective in improving diet composition and stool consistency in patients after pouch surgery and inactive disease. Improved adherence to dietary intervention is associated with personal interactions with a dietitian and the use of digital support tools.