bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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 &gt;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 &lt; 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

Abstract

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 &gt;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&lt;0.05; previous exposure to advanced therapies, aOR: 0.20, 95% CI 0.04–0.98, p&lt;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&lt;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

Abstract

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

Abstract

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

Abstract

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&lt;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

Abstract

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

Abstract

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.