bluuebunny/crossref_metadata_2025 huggingface dataset:
P0821 Effectiveness and safety of mesenchymal stem cell treatment in fistulizing Crohn’s disease: predictors of treatment success
Authors: Bacsur P , Shaham D , Serclova Z , Resál T , Farkas B , Sarlós P , Miheller P , Maharshak N , Zemel M , Shirit A , Bálint A , Fábián A , Bor R , Bősze Z , Ivány E , Szepes Z , Farkas K , Tóth I , Lázár G , Vlkova K , Tremerova A , Zuskova P , Ábrahám S , Molnár T
Published: January 2025

Background

Perianal fistulas of Crohn’s disease (CD) create a significant burden on patient lives. However, the efficacy and safety of adipose-derived mesenchymal stem cell treatment are contradicting, and real-world evidence is lacking. We aimed to examine the usability of darvadstrocel therapy in managing perianal CD.

Methods

In this retrospective multicenter study CD patients with perianal fistulas were enrolled and followed. The primary outcome was perianal clinical remission (all treated fistulas have closed) at weeks 26 and 52, while the secondary outcomes were clinical response rates (≥ 1 fistulas have closed), perianal activity (PDAI), patient satisfaction, and adverse events. The data was recorded at the baseline and weeks 12, 26, and 52. Prediction of primary outcomes was performed by logistic regression.

Results

Overall, based on the data of 223 patients (Table 1., male/female ratio: 0.48), perianal clinical remission was achieved in 78.2% and 62.3% until week 26 and 52 (Figure 1.), whereas baseline PDAI score (OR 0.75), number of fistulas (OR 0.28), and the number of weeks after preparation for surgery (OR 0.98) were associated with treatment failure. The clinical response rates were 84.8% and 79.8% at week 26 and 52. Moreover, the improvement of subjective perianal symptoms was achieved in 77.8% and 78.4% of the patients, respectively. Adverse events occurred in 13.5% of the patients, with perianal abscesses and proctalgia reported the most.

Conclusion

Effectiveness data are higher than the clinical trials. The safety profile is reassuring, and patients’ satisfaction is high. Appropriate patient selection, fistula preparation and expertise may help to achieve treatment success.
P0823 Access to an integrated Inflammatory Bowel Disease diet clinic improves patient-reported outcomes and dietary self-confidence in a tertiary service previously without dietetic services
Authors: Day A , Chu M , Scinto T , Han S , Vinci I , Hatzi M , Bryant R ,   Inflammatory Bowel Disease Research Group
Published: January 2025

Background

Disability and impaired food-related quality of life (FRQoL) is prevalent in people with inflammatory bowel disease (IBD). The aim of this study was to examine whether access to specialised IBD diet care influenced patient-reported outcomes.

Methods

This was a prospective study of an IBD Diet Clinic (IBDDC) piloted at The Queen Elizabeth Hospital, South Australia between February 2021- September 2022. During routine IBD care, adults with diet-related issues were referred to a specialised IBD dietitian and invited to complete questionnaires evaluating before- and after dietary intervention. The primary outcome was change in FRQoL (defined as 0 (poor) and 149 (exceptionally high). Secondary outcomes included change in IBD-disability index (IBD-DI), domains of diet self-management including knowledge and self-confidence and satisfaction with IBD diet care. Appropriate statistical tests were applied to descriptive, categorical, and paired data.

Results

Of 91 who attended first consult in IBDDC, 55 completed before- and after-dietetic intervention questionnaires. FRQoL scores were 64.6 (SD 16.8) at baseline and improved by 13.9 points (95% CI 8.27, 19.6; p<0.001) following dietetic intervention. Similarly, IBD-DI scores improved by 3 points (95% CI 1.78, 4.22; p<0.001), knowledge of what to eat improved by 37% (p<0.001) and confidence in self-managing diet improved by 21% (p=0.003). Satisfaction with dietary advice was high; 46/55 (83%) were satisfied or extremely satisfied and 49/55 (89%) placed high or extremely high value on continuation of an integrated IBDDC within The Queen Elizabeth Hospital IBD service.

Conclusion

In an IBD service previously without a dedicated diet clinic, access to integrated, specialised and personalised IBD dietary care led to a significant improvement in all patient-reported outcomes and a high level of patient satisfaction. Poor baseline FRQoL was identified in IBD patients without access to specialised dietetic care and through attendance to an IBDDC, FRQoL, disability indices and dietary self-confidence improved.
P0825 Combination of advanced therapies in anal fistulas of Crohn’s disease: efficacy, tolerance and predictive factors
Authors: Fathallah N , Pagano M , Skoufou M , Lazareth M , Alam A A , Barré A , Roland D , Safa Far E , Rentien A L , Chambenois E , Haouari M A , de Parades V
Published: January 2025

Background

The aim of CombioLAP study was to evaluate the efficacy and tolerance of a combination of advanced therapies (combiotherapy) in fistulizing anoperineal lesions (APL).

Methods

We conducted a retrospective study on patients treated for at least 6 months with a combiotherapy for fistulizing APL.

The primary outcome was the complete clinical remission (defined as a closure of all fistulae external openings without any discharge or pain on pressure).

The secondary outcomes were to describe in detail:

- type of combiotherapies

- complete radiological remission (defined by a MAGNIFI CD score < 6)

- tolerance and perception of treatment

- factors associated with clinical failure

Results

We included 33 patients (57.6% men, mean age 38.3 ± 13.1 years) of whom 27.3% were active smokers and 48.5% had extra-digestive manifestations. The mean time for the progression of APL was 7.8 ± 6.2 years. Half of the patients had more than one external fistula opening. Patients had undergone a mean of 5.3 ± 3.4 proctological surgeries; 53.7% of them had already had at least one fistula obturation surgery; 84.9% were in partial response or had failed at least two lines of advanced therapies.

After a median follow-up of 27.4 months [19.1-44.0] under combiotherapy, 48.5% of patients were in complete clinical remission (53.3% with associated obturation surgery).

Combiotherapy contained infliximab in 88% of cases (optimized in 82% of cases and in subcutaneous form in 52% of cases) with ustekinumab in 84% of cases (optimized in 92% of cases). An immunosuppressant was additionally associated in 21.2% of patients and long-term antibiotic therapy in 24.2% of patients (2 for refractory APL and 6 for associated hidradenitis suppurativa).

Complete radiological remission was observed in 28.6% of patients.

Treatment tolerance was defined as good to very good in 90.1% of cases. Minor adverse effects were reported in 5 patients (15.2%). No infectious or neoplastic adverse effects were reported. Improvement under treatment was considered obvious by patients in 57.6% of cases and partial in 39.4% of cases.

Associated anal ulcerations (OD [95% CI] 0.18 [0.04-0.94], p=0.042) and long-term antibiotic therapy (OD [95% CI] 0.10 [0.01-0.90], p=0.040) were predictive factors of clinical failure.

Conclusion

In refractory fistulizing APL, the most used combiotherapy was infliximab associated with ustekunimab in optimized doses, allowing complete clinical remission in 48.5% of cases and complete radiological remission in 28.6% of cases. The safety profile was good and furthermore there was good perception of treatment by most patients. Associated anal ulcerations and long-term antibiotic therapy were poor prognostic factors.
P0827 Single cell RNA sequencing analysis of specific cell subsets for predicting anti-TNF treatment response in Korean patients with ulcerative colitis
Authors: Kim H G , Jeon S R , Jung Y H , Kim J O , Choi S , Ko B M , Hwang W C
Published: January 2025

Background

The disruption of the epithelial barrier and mucosal homeostasis is key in developing ulcerative colitis (UC). Recent advances in single-cell RNA sequencing (scRNA-seq) have shed light on gene expression and cell characteristics in the intestine. However, there is limited research on Asian UC patients receiving anti-tumor necrosis factor (anti-TNF) treatment. This study sought to identify relevant cellular subsets in Korean UC patients after anti-TNF therapy using scRNA-seq.

Methods

This prospective study was conducted at two university hospitals in South Korea. To identify inflammatory cells that contribute to UC and are influenced by anti-TNF treatment, we performed scRNA-seq on sigmoid colonic biopsies from two healthy controls and six biologic-naïve UC patients prior to anti-TNF therapy. Mucosal biopsies from patients with active moderate to severe UC were collected at baseline (n=6) and again at a 52-week follow-up after anti-TNF treatment (n=2; sample collected form the responder), at which point treatment response was evaluated. A treatment responder was defined as a patient who maintained clinical remission (partial Mayo score of ≤2, with no subscore >1 and a rectal bleeding subscore of 0) at 52 weeks.

Results

After processing the scRNA-seq data, 13 clusters were identified, and cell clusters were annotated using left colon marker genes (Figure 1-a). Among the six patients evaluated at 52 weeks after anti-TNF treatment, five were treatment responders and one was a non-responder. Lower populations of ILC2 and ILC3 (Type 2 and Type 3 innate lymphoid), as well as CD8 T cells, CD4 T cells, and NK cells, were observed in the non-responder group compared to the responder group. Additionally, higher populations of mast cells, stromal fibroblasts, and endothelial cells were found in the non-responder group (Figure 1-b).

Conclusion

In Korean UC patients, anti-TNF treatment is linked to changes in tissue ILC2 and ILC3 subsets. scRNA seq analysis of tissue specimens obtained before anti-TNF use reveals stromal fibroblasts, endothelial, and mast cell-enriched genes related to anti-TNF responsiveness, underscoring the significant roles of these subsets in UC. Further confirmation is needed with larger samples and clinical validation
P0828 The impact of etrasimod on neutrophils in the ELEVATE UC clinical programme
Authors: Allez M , Verstockt B , Crosby C M , Ryan R D , Fellmann M , Kunina E , Lazin K , Dalam A B , Wu J , Karolina W , Siegmund B
Published: January 2025

Background

Neutrophils are thought to play a role in the pathogenesis of ulcerative colitis (UC); they are believed to be the principal source of faecal calprotectin and are a histological marker of disease activity in mucosal biopsies. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active UC. This post hoc analysis evaluated neutrophils in patients (pts) receiving etrasimod or placebo (PBO) in the ELEVATE UC clinical programme.

Methods

We assessed percentage changes from baseline (BL) in absolute neutrophil counts (ANC) throughout ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369)1 for all pts and those who did or did not achieve clinical remission (clinical remitters) or endoscopic improvement-histologic remission (EIH remitters) at Week (Wk) 12. Transcriptional characterisation followed by cell type deconvolution analysis from bulk RNA-seq was performed on colonic biopsies to assess for neutrophils in clinical remitters vs nonremitters (at Wk 12). Incidence of neutropenia and potential associated infections were assessed.

Results

BL blood and colonic biopsy samples, respectively, were available for 432 and 340 pts (ELEVATE UC 52) and 353 and 249 pts (ELEVATE UC 12). Pts receiving etrasimod vs PBO had significant percent decreases from BL in ANC from Wk 4 (-14.9% vs -4.9%, p<0.05; ELEVATE UC 52) and Wk 2 (-12.0% vs 0.3%, p<0.05; ELEVATE UC 12); the greatest decrease was seen for pts receiving etrasimod at Wk 12 in ELEVATE UC 12 (-16.8%) and nadir was reached at Wk 20 in ELEVATE UC 52 (-24.5%) and maintained through Wk 52. Wk 12 clinical remitters vs nonremitters receiving etrasimod had significantly greater percent decrease in ANC from BL at most time points (p<0.05; Figure); a similar trend was seen for EIH remitters vs nonremitters. Colonic neutrophils were also significantly decreased at Wk 12 vs BL for pts receiving etrasimod (false discovery rate [FDR] <0.05) but not PBO, and for clinical remitters vs nonremitters receiving etrasimod (FDR <0.05). Across both trials, nine (etrasimod) and four (PBO) pts had neutrophil counts <1 × 109/L at any post-BL assessment. Of these pts, none reported subsequent serious, severe or opportunistic infections; one pt receiving etrasimod experienced a nonserious infection ≤60 days after reported neutropenia.

Conclusion

Our data support a relationship between decreased circulating and mucosal neutrophil levels and clinical and endoscopic improvement with etrasimod treatment in pts with UC, while showing a low likelihood of neutropenia.

References

1. Sandborn WJ et al. Lancet 2023; 401: 1159–1171.

Pfizer’s generative artificial intelligence tool MAIA was used to assist production of the abstract first draft. Authors reviewed/edited and take responsibility for the content.
P0833 Trajectories of response in patients with moderately-to-severely active Crohn’s disease treated with mirikizumab or ustekinumab: Post hoc results from the VIVID-1 study
Authors: Schreiber S W , Clemow D B , Yu G , Keefer L A , Ananthakrishnan A N , D’Haens G , Deepak P , Kocchar G S , Melmed G Y , Chen Y F , Moses R E
Published: January 2025

Background

Mirikizumab (MIRI), an anti-IL-23p19 antibody, demonstrated robust efficacy in improving clinical and endoscopic endpoints with an acceptable safety profile1. In patients with moderate-to-severely active Crohn’s disease (CD), we explored the trajectory of response to MIRI or ustekinumab (USTE), an anti-IL-23p19p40 active comparator.

Methods

MIRI (N=572) and USTE (N=285) patients described previously1 were assessed via Growth Mixture Model to identify distinct clusters based on individual patient response trajectories. The Growth Mixture Model was first fit with MIRI only patient data with standardized beta link function to accommodate the non-Gaussian outcomes. Then the model was run with USTE only patient data based on the model parameter settings from the MIRI model to allow comparison. Change from baseline in Crohn’s Disease Activity Index (CDAI) total score was used in the Growth Mixture Model to identify trajectories. Week 52 clinical endpoints were assessed by trajectory group for MIRI and USTE. Modified baseline observation carried forward imputation used.

Results

There were four response trajectory clusters identified for MIRI, which were then compared to USTE: Super Responder (MIRI/USTE: 18.4%/10.9%), Responder (MIRI/USTE: 22.4%/13.0%), Delayed Responder (MIRI/USTE, 29.5%/31.2%), and Non/Incomplete Responder (MIRI/USTE, 29.7%/44.9%) (Figure 1). The proportion of Super Responders plus Responders was greater for MIRI vs USTE (40.7% vs 23.9%) and the proportion of Non/Incomplete Responders less (29.7% vs 44.9%). The proportion of patients achieving Week 52 clinical, endoscopic, and histologic endpoints was generally greatest for Super Responders followed by Responders and then Delayed Responders (Table 1). The proportion of patients achieving these endpoints for Super Responders + Responders was generally greater for MIRI vs USTE, in particular histologic response (70% vs 60%) and remission (36% vs 22%).

Conclusion

The overall response rate was 70.3% for MIRI and 55.1% for USTE. For the 4 MIRI symptom response trajectory groups – Super Responder, Responder, Delayed Responder, and Non/Incomplete Responder – the proportion of Super Responders plus Responders was greater for MIRI vs USTE and the proportion of Non/Incomplete Responders was less for MIRI vs USTE, while the proportion of patients achieving clinical endpoints for MIRI was generally numerically greater than USTE for Super Responders plus Responders.

References

1.M Ferrante, S Danese, M Chen, et al. OP05 Primary efficacy and safety of mirikizumab in moderate to severe Crohn’s Disease: results of the treat-through VIVID 1 study, Journal of Crohn’s and Colitis, Volume 18, Issue Supplement_1, January 2024, Pages i7–i9, https://doi.org/10.1093/ecco-jcc/jjad212.0005.
P0834 Mucosal improvement and histologic healing with amiselimod for active Ulcerative Colitis: a phase 2, randomised, placebo-controlled trial
Authors: Schreiber S W , Laitman A P , Heimanson Z , Israel R J , Lee J , Hanauer S B
Published: January 2025

Background

Amiselimod is an investigational oral, sphingosine 1-phosphate (S1P) receptor modulator (highest affinity for S1P1, followed by S1P5) whose immunomodulatory mechanism of action includes decreasing circulating peripheral lymphocytes. The study objective was to assess the endoscopic/histologic outcomes of 2 dose regimens of amiselimod for mild to moderate UC.

Methods

Patients (age, 18-75 y) with mild to moderate UC (modified Mayo Score [MMS], 3-8) with an endoscopic subscore of ≥2 and active disease extending ≥15 cm from anal verge were enrolled in a phase 2, randomised, double-blind, placebo-controlled trial. Patients were randomly assigned to: (1) amiselimod 0.4 mg once daily (QD) for 2 weeks (loading dose), then 0.2 mg QD for 10 weeks (group A); (2) amiselimod 0.8 mg QD for 2 weeks (loading dose), then 0.4 mg QD for 10 weeks (group B); or (3) placebo QD. Stable maintained doses of oral/rectal 5-aminosalicylate or oral corticosteroids (≤20 mg/day prednisolone dose equivalent) were permitted. Endpoints included change from baseline in MMS (primary), and percentage of patients with endoscopic improvement (Mayo endoscopic subscore ≤1 [secondary]), histologic remission (Geboes index score of <2.0 [original Geboes Score; exploratory]), or mucosal healing (Mayo endoscopic subscore ≤1 and Geboes index score of <2.0; exploratory) at Week 12.

Results

A total of 321 patients were included (107 per group). For groups A, B, and placebo, the mean (SD) age was 40.6 (14.5) y, 41.6 (12.4) y, and 40.5 (12.4) y, respectively; 41.1%, 40.2%, and 43.0% were female, respectively. Most patients had moderate UC (80.4%, 79.4%, and 79.4%, respectively) and the baseline median (range) MMS score was 6 (3-8) for each group. For the primary endpoint, a significant improvement in mean MMS from baseline at Week 12 was observed for Group A (-2.3) and Group B (-2.3) vs placebo (-1.6; P<0.01 for both vs placebo). Both amiselimod groups had a significantly larger percentage of patients with endoscopic improvement vs placebo at Week 12 (P<0.01 for both vs placebo; Figure). Significantly higher rates of histologic remission were achieved in patients in both amiselimod groups vs placebo at Week 12 (P≤0.03 for both vs placebo; Figure). As well, significantly more patients in Group A (15.0%) and Group B (15.9%) vs placebo (5.6%) had mucosal healing at Week 12 (P=0.02 for both vs placebo).The most common haematologic adverse events with amiselimod (group A, group B) vs placebo were leucopenia (8.4%, 15.9% vs 0%), anaemia (5.6%, 3.7% vs 3.7%), and neutropenia (1.9%, 5.6% vs 0%).

Conclusion

Both 12-week dosing regimens of amiselimod for UC were superior to placebo for inducing mucosal improvement and histologic healing with a favourable safety profile.
P0840 Health related quality of life (HRQOL) in patients with ulcerative colitis (UC) treated with obefazimod: the phase 2 open label maintenance study
Authors: Vermeire S , Sands B E , Rabbat C , Shan K , Dolan C M , Cataldi F , Jacobstein D , Fine J T
Published: January 2025

Background

Obefazimod is an investigational, oral, once-daily (QD), small molecule which enhances expression of microRNA-124 and demonstrated efficacy in patients (pts) with moderately to severely active UC at Week 8 of a phase 2b induction trial. The proportion of pts achieving clinical endpoints increased at Week 48 in the subsequent open-label maintenance study (OLM). Here we report long term effects of obefazimod on HRQOL.

Methods

In the phase 2b trial, pts were randomized 1:1:1:1 to receive 100 mg, 50 mg, or 25 mg oral, obefazimod or placebo (PBO) QD for 16 weeks. The primary endpoint was at Week 8. If pts completed the 16-week induction trial, regardless of clinical/symptomatic response or randomized dose received, they could be enrolled in the OLM and receive 50 mg QD through Week 48.

Pts completed the IBDQ, a disease-specific HRQOL questionnaire consisting of 32 items across 4 domains (Emotional functioning, Bowel symptoms, Social functioning, Systemic symptoms) at baseline and Week 8 of the induction trial and Week 48 of the OLM. The IBDQ items are assessed on a 7-point scale with scores ranging from 32 to 244; higher scores reflect better well-being. Mean value by visit and mean change in IBDQ from Week 8 to 48 were reported descriptively. The proportion of pts with IBDQ remission (IBDQ total score ³170) at Weeks 8 and 48 and IBDQ response ( ³16 point increase in IBDQ total score) from Week 8 to 48 were determined. Pts that received at least 1 dose and had baseline IBDQ data were included in this analysis. Data were analyzed as observed.

Results

222 pts completed the induction trial, 217 continued in the OLM. 178 pts were included in this analysis. Across IBDQ total score and domains, further improvements in HRQOL were obtained after Week 8 with continued obefazimod treatment to Week 48. The largest increases were observed in pts who received PBO in the induction trial and then 50 mg in the OLM. Mean change from Week 8 to 48 in IBDQ total score was (mean (SD)) = 25.6 (28.8), 29.7 (34.9), 17.0 (26.5), and 38.7 (30.3) for pts in the 100 mg, 50 mg, 25 mg, and PBO groups, respectively, in the induction trial (Table). At Week 48, IBDQ remission was achieved by over 80% of pts, regardless of induction treatment, as compared to 42.1-62.7% at Week 8. At Week 48 an IBDQ response from Week 8 was achieved in 48.7%, 66.7%, 46.9%, 73.9% of pts in the 100 mg, 50 mg, 25 mg, and PBO groups, respectively.

Conclusion

Improvements in HRQOL were achieved and maintained with obefazimod treatment in adults with moderately to severely active UC, consistent with clinical efficacy endpoints.

Table. IBDQ endpoints in the OLE study
P0841 Hospitalisation and surgery rates in patients with Ulcerative Colitis and Crohn’s disease treated with subcutaneous vedolizumab: Long-term findings from the VISIBLE OLE study
Authors: Vermeire S , Jones S , Velazco N , Agboton C , Wojtowicz A M , Young L , Phillips R , Loftus- Jr. E V , Danese S , D’Haens G
Published: January 2025

Background

Vedolizumab (VDZ) is a gut selective, monoclonal anti-α4β7 integrin antibody approved for the treatment of moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD). The subcutaneous (SC) formulation of VDZ was evaluated during the Phase 3 VISIBLE 1 and 2 studies. This analysis reports hospitalisations and surgeries among patients (pts) with UC or CD treated with VDZ SC enrolled in the VISIBLE open-label extension (OLE) study.

Methods

Pts who participated in VISIBLE 1 or VISIBLE 2 were eligible to enrol in VISIBLE OLE (NCT02620046) and received VDZ SC 108mg every 2 weeks (Q2W) or weekly. Patients were grouped according to their scenario in VISIBLE 1/2: Pts who withdrew between week (W) 6 and W52 (Scenario 1); pts who completed 52 weeks of treatment with VDZ or placebo (Scenario 2); pts without a clinical response at W6 but who responded at W14 and were not randomised (Scenario 3). The proportions of patients who experienced UC or CD related hospitalisation and/or surgery during VISIBLE OLE were assessed by scenario and treatment received during VISIBLE 1/2.

Results

A total of 288 pts with UC and 458 with CD enrolled in the VISIBLE OLE. The mean (min., max.) duration of VDZ exposure during VISIBLE OLE was 1276.7 days (127, 2577 days) among pts with UC and 1110.0 days (127, 2770 days) among pts with CD. The proportions of pts who had a UC or CD related hospitalisation or surgery during VISIBLE OLE are displayed in Table 1. Across all scenarios, a total of 8.3% (24/288) of pts with UC had a related hospitalisation. In total, 3/288 pts (1.0%) with UC (from Scenarios 1 and 3) had a colectomy. No pts with UC from Scenario 2 had a colectomy. Among pts with CD, a total of 13.1% (60/458) had a related hospitalisation. A total of 19 pts (4.1%) with CD had bowel surgery. Higher rates of IBD related hospitalisations and surgeries were observed in Scenario 1, both in pts with UC and with CD.

Conclusion

Findings from VISIBLE OLE showed that few pts with UC and CD treated with long-term VDZ SC required IBD related hospitalisations over the course of the study. Notably, very few patients with UC or CD required colectomies or bowel surgery.
P0846 A patient’s perspective on the use of exclusive enteral nutrition (EEN) for the treatment of paediatric Crohn’s Disease
Authors: Martin A , O’meara M
Published: January 2025

Background

Crohn’s Disease (CD) is a chronic condition and can result in the inflammation of any part of the gut. If left untreated, children diagnosed with CD are at increased risk of nutrient malabsorption and poor growth. The first-line treatment for CD is a 6-week dietary treatment called Exclusive Enteral Nutrition (EEN). This diet requires patients to stop eating food and switch to taking prescribed nutritional drinks, to achieve outcomes of resolving malabsorption symptoms and improving growth. This treatment is managed exclusively by dietitians. The aim of this study is to acquire an in depth understanding of the paediatric patient experience with EEN; identifying challenges and empowerment strategies that help increase patient adherence to the EEN treatment course.

Methods

Ethical approval was obtained from the CHI Ethics Committee in October 2023. The design of this study is a mixed-research method that focuses on collecting both qualitative and quantitative data. Participants of the study include patients of both sexes and all ethnicities, between 1-17years old, who were diagnosed with CD and advised to complete their first course of EEN during January 2022 and October 2023. An anonymised survey with 25 questions total was used to gather the information.

Results

Of the 116 patients who were approached to take part in the study, 47% of participants completed it. Two main themes were identified: (i) barriers to EEN compliance (subthemes included “feelings of isolation, taste/texture/smell of drinks and missing food), (ii) empowerment strategies for EEN (subthemes included drink preparation techniques, eliminating temptation, wide flavour choice, external support and health improvements). Of the 79% of patients who completed a full course of EEN; 55% found it ‘difficult’ and 60% reported that "they would attempt it again if required".

Conclusion

This study shows that patients find EEN to be a challenging diet which can have physical, emotional, and social impacts on aspects of the child’s life. Empowerment strategies such as external support (from family, friends and dietitians), adequate drink preparation and an awareness of associated health outcomes are imperative to help patients complete EEN. These findings are a valuable addition to the current limited knowledge base in this area.
P0847 Comparative efficacy on steroid-free remission of pharmacological therapies for moderate-to-severe Ulcerative Colitis: A systematic review and network meta-analysis
Authors: Katsoula A , Paschos P , Malandris K , Giouleme O , Tsapas A ,   This study was funded by a research grant 2020EOMIFNEp5 from the Hellenic Group for the Study of IBD (EOMIFNE)
Published: January 2025

Background

We performed a systematic review and network meta-analysis to assess the comparative efficacy of pharmacological therapies in achieving steroid-free remission for patients with moderate-to-severe ulcerative colitis (UC).

Methods

We conducted a comprehensive search of electronic databases and grey literature up to September 2024 to identify randomized controlled trials in adults with moderate-to-severe UC, comparing advanced therapies. The primary endpoint was corticosteroid-free clinical remission at the end of maintenance therapy. We combined direct and indirect evidence through multivariate random-effects network meta-analyses, and the relative ranking of treatments was assessed using surface under the cumulative ranking (SUCRA) probabilities. Additionally, subgroup analyses were performed based on prior anti-TNF exposure. Confidence in the estimates was evaluated using the CINeMA (Confidence in Network Meta-Analysis) framework.

Results

We included 22 studies (5 infliximab, 2 adalimumab, 2 golimumab, 3 vedolizumab, 1 ustekinumab, 1 ozanimod, 2 filgotinib, 1 upadacitinib, 1 etrasimod, 1 mirikizumab, 1 tofacitinib, 1 risankizumab, 1 guselkumab). Randomized controlled trials were categorized into two study designs: re-randomization of patients after an induction period and treat-through patients. All interventions except golimumab and filgotinib 100mg were superior to placebo for steroid-free remission in re-randomized patients (Figure 1).

In re-randomized anti-TNF-naive patients, no agents were superior to placebo, while in anti-TNF-experienced patients, upadacitinib, risankizumab, and mirikizumab had significantly higher remission rates than placebo. In treat-through patients, all interventions except vedolizumab were superior to placebo for steroid-free remission (Figure 2).

Etrasimod achieved significantly higher remission rates than placebo in treat-through anti-TNF-experienced patients, while etrasimod and infliximab achieved significantly higher rates in re-randomized anti-TNF-naive patients. Regarding efficacy, upadacitinib 30 mg/day ranked first for re-randomized patients (SUCRA 94.4%), while etrasimod 2 mg/day ranked first for treat-through patients (SUCRA 91%). Our confidence in estimates was very low due to imprecision and high risk of bias in included studies.

Conclusion

Very low-quality evidence supports the efficacy of all interventions except golimumab, vedolizumab, and filgotinib 100mg for steroid-free remission. Upadacitinib 30 mg/day and etrasimod 2 mg/day were ranked highest for efficacy in re-randomized and treat-through patients, respectively.
P0853 Decrease in fecal calprotectin and C-reactive protein levels correlate with improved clinical outcomes in patients with moderately to severely active Crohn’s disease treated with mirikizumab
Authors: Charabaty A , Kayal M , Kelly C R , Cohen B L , D’Haens G , Hart A , Chan-Diehl F , Yu G , Brogan Y , Protic M , Moses R , Fisher D , Travis S
Published: January 2025

Background

Mirikizumab (miri), an anti-IL-23p19 antibody, has shown efficacy in treatment of patients with moderately to severely active Crohn’s disease (CD) in a Phase 3 study VIVID-1 (NCT03926130). We evaluated the associations of inflammatory biomarkers, fecal calprotectin (FC) and C-reactive protein (CRP), with clinical, endoscopic, and histologic improvement in patients randomised to miri.

Methods

VIVID-1 achieved the primary and key secondary endpoints published previously1. The mean change from baseline in FC and CRP was compared between patients who achieved selected clinical, endoscopic, histologic, and combined endoscopic and histologic (endo-histo) endpoints versus those who did not achieve such endpoints who were randomised to miri using t-test. At week 12 (W12) and W52, clinical response by PRO (Patient Reported Outcome), clinical response by CDAI (Crohn’s Disease Activity Index), clinical remission by PRO, clinical remission by CDAI, endoscopic response, histologic response, and the composite of endo-histo response were evaluated. At W52, additional endpoints of endoscopic remission, histologic remission, and the composite of endo-histo remission were evaluated. Non-responder imputation (NRI) was used for binary missing data and modified baseline observation carried forward was used for continuous missing data.

Results

At W12, there was statistically greater improvement in both FC and CRP in all endpoints (Figure 1). Improvement in FC associated with endoscopic and histological improvement (p<0.001) more closely than CRP (p<0.05), while CRP associated more closely with clinical endpoints. At W52, change in FC and CRP from baseline were significantly associated with achieving clinical response by PRO, clinical response by CDAI, clinical remission by PRO, clinical remission by CDAI, endoscopic response and remission, histologic response and remission, and the composite of endo-histo response and remission (FC, p<0.001 for all endpoints; CRP, p<0.001 for all endpoints but histologic remission and endo-histo remission which have p<0.05) (Figure 2).

Conclusion

At W12 and W52, change from baseline of FC was better associated with endoscopic and histological improvement while decrease of CRP was better associated with clinical outcomes. These results further support non-invasive approaches to monitoring response of CD to treatment.

References

1.M Ferrante, S Danese, M Chen, et al. OP05 Primary efficacy and safety of mirikizumab in moderate to severe Crohn’s Disease: results of the treat-through VIVID 1 study, Journal of Crohn’s and Colitis, Volume 18, Issue Supplement_1, January 2024, Pages i7–i9, https://doi.org/10.1093/ecco-jcc/jjad212.0005
P0854 The Effectiveness of Risankizumab as Induction Therapy for Crohn’s Disease: Data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD)
Authors: Macaluso F S , Renna S , Fries W , Viola A , Cappello M , Salerno I A , Mocciaro F , Scrivo B , Giangreco E , Ferracane C , Minissale M G , Distefano M E , Tortorella V , Termini A , Bertoncello L , Orlando A ,   Sicilian Network for Inflammatory Bowel Disease (SN-IBD)
Published: January 2025

Background

Real-world studies are necessary to complement the evidence from randomized controlled trials. Currently, real-world data on the effectiveness of Risankizumab (RZB) for the treatment of Crohn’s Disease (CD) are scarce.

Methods

We designed a real-world, multicenter, observational study involving CD patients of the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) to assess the effectiveness of RZB induction therapy in clinical practice. All consecutive adult (≥18 years) patients with active CD treated with RZB from February 2024 (the date on which RZB became available for clinical practice in Sicily) who completed the induction therapy (12 weeks) were included. The effectiveness of the induction therapy was evaluated at 12 weeks, and all adverse events were reported. The effectiveness outcomes were steroid-free clinical remission (Harvey-Bradshaw Index < 5 and no steroids use) and clinical response (reduction of Harvey-Bradshaw Index ≥ 3 compared with baseline, with a concomitant reduction of at least ≥ 50% of steroid dosage).

Results

74 consecutive CD patients (males: 43.2%; mean age: 43.8 ± 14.9 years) were included. All patients had at least one previous failure with a biological therapy, while 21 (28.8%) and 20 (27.0%) patients experienced three or four previous lines of biologics, respectively. At week 12, steroid-free clinical remission was obtained in 48.6% of patients, clinical response in 17.6% of patients (overall clinical benefit: 66.2%), while nonresponse was reported in 33.8% of patients. No significant difference of clinical benefit was found comparing patients who were previously treated with one or two biologics with those who were previously treated with three or four biologics (75.7% vs. 58.5%; p=0.12). Conversely, the difference of clinical benefit was significant when patients who were previously treated with only one biologic were compared with those who were treated with two or more previous lines (91.7 vs. 61.3%; p=0.04). Two adverse events were reported: one case of mild Covid-19, and one patients who suffered from a generalized edema leading to drug withdrawal.

Conclusion

Our multicenter cohort study confirmed the efficacy of RZB in inducing remission in patients with CD, particularly in those with previous therapeutic failures with biologics. Interestingly, the best results were observed in patients with only one previous therapeutic failure, i.e. as second-line therapy after a failure with one TNF-inhibitor.
P0861 Comparative effectiveness and safety of ustekinumab versus anti-tumour necrosis Factor agents as first- or second-line biologics in Crohn´s disease: a real-world multicentric observational study
Authors: Ferreira S , Serafim Parra R , Yukie Sassaki L , Kurtz de Mello M , Luz Parente J M , Bafutto M , Cancela Penna F G , Penna Pinho L , de Sá Brito Fróes R , Tricarico Gasparetti Junior Gasparetti N L , Andrade Chebli L , Tiburcio Alves Junior A J , Firmino Nóbrega F J , Botelho Quaresma A , Mattioli Nicollelli G , Galhardi Gasparini R , de Medeiros Dutra R , Oliveira Magro D , Gardere Camargo M , Palha Dias Parente L , Féres O , de Almeida Troncon L E , Kotze P G , Fonseca Chebli J M
Published: January 2025

Background

Ustekinumab (UST), an antibody targeting the p40 subunit of interleukin-12/23, has demonstrated efficacy in patients with Crohn’s disease (CD). However, comparative real-world data regarding the positioning of biologic therapies, particularly UST versus anti-tumour necrosis factor (TNF) agents, remain limited. This study aimed to compare the effectiveness and safety of UST and anti-TNF agents in biologic-naïve and biologic-failure CD patients.

Methods

A multicentre retrospective cohort study was conducted, including patients with moderate to severe CD initiating first- or second-line biologic treatment with UST or anti-TNF agents [infliximab (IFX) or adalimumab (ADA)]. Propensity score adjustment (1/PS) was applied to address confounders. Primary endpoints were clinical remission (Harvey-Bradshaw Index ≤3), endoscopic remission (SES-CD ≤3 or Rutgeerts score I0), and steroid-free clinical remission at week 52. Secondary outcomes included clinical response, primary/secondary loss of response, treatment persistence, biochemical remission, adverse events (AEs), hospitalisation, and surgeries.

Results

A total of 536 CD patients (172 IFX, 132 ADA, 236 UST) were analysed. Clinical remission at week 52 was achieved by 78.1% of UST and 75.7% of anti-TNF patients in the biologic-naïve group (p=0.25), and 52.2% of UST and 50.5% of anti-TNF in biologic-failure patients (p=0.31). Steroid-free clinical remission rates were similar between UST and anti-TNF groups: 80.5% vs 80.1% (p=0.99) in biologic-naïve and 81.2% vs 77.3% (p=0.46) in biologic-failure patients. Endoscopic remission was observed in 74.8% of UST vs 68.8% of anti-TNF patients (p=0.81) in biologic-naïve, and 50.6% vs 46.8% (p=0.72) in biologic-failure. Serious AEs were more frequent with anti-TNF agents in biologic-failure patients (28.3% vs 12.5%; p<0.01). UST demonstrated higher treatment persistence in biologic-naïve patients (96.9% vs 80.8%; p=0.029) and lower CD relapse rates (3.08% vs 11.11%; p=0.01).

Conclusion

UST and anti-TNF agents exhibit comparable effectiveness for CD treatment regardless of prior biologic exposure. UST showed superior treatment persistence and a better safety profile, particularly in biologic-naïve patients.
P0862 Elderly-onset inflammatory bowel disease (IBD) differs in disease characteristics and treatment exposures from adult-onset IBD
Authors: Granot M , Kopylov U , Nachum N , Krauthammer A , Tal B , Abitbol C M , Ben-Horin S , Weiss B , Haberman Y
Published: January 2025

Background

Elderly-onset inflammatory bowel disease (IBD) patients (age ≥60 at diagnosis) have unique characteristics and require special considerations. Using a real-life registry-based cohort, we compared disease characteristics and treatment exposures between adult-onset and elderly-onset IBD.

Methods

We analyzed data from a comprehensive IBD registry, comparing demographics, disease characteristics, and treatments between adult-onset (diagnosed at 18≤ age <60 years) and elderly-onset (age ≥60 at diagnosis) IBD patients diagnosed during 2000-2022 and with ≥12 months follow-up.

Results

We included 3307 adult IBD patients diagnosed above the age of 18 years. The median follow-up time was six years. 290 (9%) were elderly-onset IBD. In the elderly-onset group, there was a higher fraction of UC, 38.3% (111/290 IBD), compared with only 31.4% (949/3017) UC cases in the adult-onset group (p=0.02). Similarly, within the CD group, patients with elderly-onset compared to adult-onset CD presented with more colonic L2 disease (21% vs. 12%, p<0.001) and less ileocolonic L3 disease (14% vs. 29%, p<0.001). Additionally, patients with elderly-onset CD compared to adult-onset CD presented less frequently with penetrating B3 phenotype (7.4% vs. 19%, p<0.001) and with less perianal involvement (10% vs. 20%, p<0.001), respectively. Elderly-onset CD and UC patients received significantly more 5ASA (36% vs. 17%, p<0.001 in CD and 75% vs. 63%, p=0.02 in UC) and considerably fewer biologics and/or JAK inhibitors (37% vs. 56%, <0.001 in CD and 20% vs. 34%, p=0.02 in UC). There was no significant difference in surgery rates between the two age groups for CD and UC. Kaplan-Meier curve and Cox proportional hazard analyses showed significantly higher 15-year (180 months) biologic-free survival from diagnoses among elderly-onset compared to adult-onset IBD (p<0.001, Figure 1 for CD and Figure 2 for UC). There were differences between the types of first-line biologics received between the two groups, with adult-onset IBD receiving significantly more anti-TNF class medications (CD: 90% vs. 20%, p<0.001, UC 63% vs. 23%, p<0.001) and elderly-onset IBD receiving more Vedolizumab as first-line biologic (CD: 46% vs. 10%, p<0.001, UC: 68% vs. 38%, p<0.001).

Conclusion

This real-world registry analysis reveals that elderly-onset IBD is characterized by a higher prevalence of UC and colonic-only L2 CD, with less CD B3 penetrating and perianal disease. Treatment strategies in elderly-onset IBD favor 5-ASA and show reduced biologic use, with preferences for Vedolizumab vs anti-TNFs in elderly-onset IBD.
P0865 Impact of assay on the predictive performance of model-informed precision dosing of ustekinumab in patients with Crohn’s disease
Authors: Zhang W , Dervieux T , Thomas D , Ferrante M , Vermeire S , Dreesen E
Published: January 2025

Background

Therapeutic drug monitoring (TDM) concentrations of ustekinumab measured by homogeneous mobility shift assay (HMSA) are significantly higher than those measured by enzyme-linked immunosorbent assay (ELISA) [1]. However, the impact of the assay format on the predictive performance of model-informed precision dosing (MIPD) is unknown.

Methods

Data from 83 patients with Crohn's disease (CD) were repurposed [2]. Patients received an intravenous ustekinumab induction and subcutaneous maintenance injection every eight weeks. Serum samples were collected at week (w)4, w8, w16, and w24. The ustekinumab concentration was measured in each sample using HMSA (Data_HMSA) and ELISA (Data_ELISA). Two corresponding population pharmacokinetics (popPK) models were developed: Model_HMSA (unpublished) and Model_ELISA [2].

Bayesian forecasting was performed with both datasets and models under four scenarios: (1) w8 predicting w16, (2) w8 predicting w24, (3) w16 predicting w24, and (4) w8 and w16 predicting w24. Accuracy and precision were assessed using relative bias (rBias) and relative root mean square error (rRMSE), respectively. Clinically acceptable rBias was ±20% with a 95% confidence interval (CI) including zero. The rRMSE threshold was 30%. Regression and Bland–Altman plots were used to examine correlation and agreement between forecasted ustekinumab clearance estimates.

Results

When datasets and models were matched (Data_HMSA–Model_HMSA, Data_ELISA–Model_ELISA), rBias met clinical standards across all scenarios (Figure 1A). However, accuracy was worse when datasets and models were mismatched (Data_HMSA–Model_ELISA, Data_ELISA–Model_HMSA). Precision was highest using Data_HMSA, irrespective of the assay that was used to build the model (Figure 1B).

Model_HMSA consistently overestimated concentrations in Data_ELISA, with rBias 8.54% [95% CI 0.149%–16.9%], 18.5% [6.81%–30.1%], 27.4% [16.9%–37.8%], and 19.7% [8.88%–30.6%] for scenarios 1, 2, 3, and 4, respectively. In contrast, Model_ELISA underestimated concentrations in Data_HMSA for scenarios 3 and 4, with rBias -11.2% [-17.2%– -5.13%] and -10.8% [-17.2%– -4.45%], though results were clinically acceptable for scenarios 1 and 2.

Clearance estimates were systematically lower using Model_HMSA than Model_ELISA, with high determination coefficients (R² range 0.94–1.00) (Figure 2A). Bland–Altman plots showed poor agreement between clearance estimates obtained from two models (Figure 2B).

Conclusion

This study is the first to assess the impact of the assay format on the performance of MIPD. Our findings highlight the importance of matching the TDM assay format with the assay format used to build the popPK model.

References

[1]Verdon et al.J Can Assoc Gastroenterol. 2020;4(2):73-77.

[2]Wang et al. Br J Clin Pharmacol. 2022;88(1):323-335.
P0867 Persistence of treatment effect in patients with Ulcerative Colitis and Crohn’s disease: Long-term results from the VISIBLE OLE study
Authors: Vermeire S , Jones S , Velazco N , Agboton C , Wojtowicz A M , Young L , Phillips R , Loftus- Jr. E V , Danese S , D’Haens G
Published: January 2025

Background

Vedolizumab (VDZ) is a gut selective, monoclonal anti-α4β7 integrin antibody approved for the treatment of moderate to severe ulcerative colitis (UC) or Crohn’s disease (CD). The subcutaneous (SC) formulation of VDZ was evaluated during the Phase 3 VISIBLE 1 and 2 studies. We report the long-term efficacy among patients (pts) with UC or CD treated with VDZ SC in the VISIBLE open-label extension (OLE) study.

Methods

Pts with UC or CD in VISIBLE 1/2 could enrol in VISIBLE OLE (NCT02620046). Pts in VISIBLE 1/2 who completed 52 weeks(W) of treatment with VDZ or placebo (randomised completers) and pts without clinical response at W6 who responded at W14 (non-randomised responders) received VDZ SC 108mg every 2W (Q2W) in the OLE. Pts with worsening disease were escalated to QW dosing. Clinical remission (partial Mayo score ≤2, no subscore >1 in UC; HBI score ≤4 in CD) up to W168 was assessed (pts with missing data or escalated to QW dosing were imputed as non-response, irrespective of clinical status). The number of pts who regained clinical response when escalated to QW dosing was also assessed. Results were summarized by prior VISIBLE 1/2 treatment groups.

Results

Data from 231 pts with UC and 344 pts with CD were included. In pts with UC, baseline OLE clinical remission rates were 55.0%, 91.3% and 77.1% among randomised completers (N=124) previously treated with placebo, VDZ SC and VDZ IV in VISIBLE 1, respectively. At W168, 40.0%, 56.5% and 62.9%, respectively, were in clinical remission on Q2W dosing. In non-randomised responders with UC (N=107), 57.0% were in clinical remission at baseline and 29.9% at W168 (Figure). In pts with CD, baseline OLE clinical remission rates were 60.3% and 62.0% among randomised completers (N=226) previously treated with placebo and VDZ SC in VISIBLE 2. At W168, 32.4% and 37.3% were in clinical remission on Q2W dosing. In non-randomised responders with CD (N=118), 57.6% were in clinical remission at baseline and 27.1% at W168 (Figure). In pts with UC escalated to QW dosing, 22.2% and 38.1% achieved clinical remission and response at W8 after transitioning to QW. Among pts with CD escalated to QW dosing, 38.6% and 53.5% achieved clinical remission and response by W8 after transitioning to QW. Higher rates of remission and response were noted in VDZ completers than non-randomised responders. No new long-term safety signals were noted with VDZ SC vs IV, except for injection site reactions.

Conclusion

The clinical benefit of VDZ SC was maintained long-term during VISIBLE OLE. A subset of pts who escalated to QW dosing regained response. Findings support VDZ SC as a treatment option for patients with UC or CD who require long-term maintenance therapy.