bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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&lt;0.05; ELEVATE UC 52) and Wk 2 (-12.0% vs 0.3%, p&lt;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&lt;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] &lt;0.05) but not PBO, and for clinical remitters vs nonremitters receiving etrasimod (FDR &lt;0.05). Across both trials, nine (etrasimod) and four (PBO) pts had neutrophil counts &lt;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

Abstract

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

Abstract

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 &lt;2.0 [original Geboes Score; exploratory]), or mucosal healing (Mayo endoscopic subscore ≤1 and Geboes index score of &lt;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&lt;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&lt;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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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&lt;0.001) more closely than CRP (p&lt;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&lt;0.001 for all endpoints; CRP, p&lt;0.001 for all endpoints but histologic remission and endo-histo remission which have p&lt;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