bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0813 Integrated summary of safety of obefazimod for patients with moderately to severely active ulcerative colitis
Authors: Vermeire S , Peyrin-Biroulet L , Danese S , Dubinsky M , Dulai P S , Tilg H , Siegmund B , Hisamatsu T , Shan K , Jacobstein D , Cataldi F , Rabbat C , Sands B E 
Published: January 2025

Abstract

Background
Obefazimod is an oral, once-daily (QD), small molecule which enhances expression of microRNA-124 and is currently in phase 3 clinical trials for the treatment of patients with moderately to severely active ulcerative colitis (UC) [1]. Obefazimod demonstrated efficacy and safety in patients with UC across 4 clinical studies: two placebo-controlled Phase 2 induction trials, and two subsequent open-label maintenance (OLM) studies [2, 3]. Here we report an integrated safety analysis of those studies in the UC clinical program.

Methods
Exposure-adjusted incidence rates (EAIRs per patients-years [PY]) of treatment emergent adverse events (TEAEs) were examined among patients from the induction trials (NCT03093259, NCT03760003), and the OLM studies (NCT03368118, NCT04023396). Patients received one of three obefazimod doses (25mg, 50mg or 100mg QD) or placebo during induction, and all patients received 50 mg QD during OLM studies.

Results
Demographics and disease characteristics were similar among treatment groups. Exposure for all obefazimod-treated patients (N=274) was 440.1 PY including induction and maintenance periods. EAIR of TEAEs per PY was 1.40 in obefazimod-treated patients and 2.40 in placebo-treated patients (N=73), with TEAEs occurring in 78.5% and 47.9% of patients, respectively (Table 1). The most common TEAEs (EAIR per PY ≥ 0.05) in all obefazimod-treated patients included headache, Covid-19, ulcerative colitis, nasopharyngitis, and nausea. For each of these TEAEs, the incidence per PY was numerically lower in the group of all obefazimod-treated patients relative to placebo.

Conclusion
This integrated safety analysis of the 4 completed studies in the obefazimod UC clinical program indicates that exposure-adjusted incidence rates of TEAEs were generally numerically lower among patients treated with obefazimod relative to placebo. Integrated safety data further support a favorable safety and tolerability profile.

References
1. Vermeire S, et al. J Crohns Colitis. 2023; 17: 1689-1697
2. Vermeire S, et al. Gastroenterology 2021; 160: 2595-2598
3. Vermeire S, et al. The Lancet Gastroenterology & Hepatology. 2022; 7: 1024-1035.
P0814 Transmural healing in Crohn’s disease: Real-world insights from the SUNRISE study on vedolizumab using intestinal ultrasonography
Authors: Carter D , Fiorino G , Biedermann P , Cassanelli F , Meyer M , Novak K L , Kopylov U 
Published: January 2025

Abstract

Background
The use of patient-centric monitoring modalities for assessing therapies, such as vedolizumab (VDZ), are of growing interest to optimize disease outcomes in patients (pts) with Crohn’s disease (CD). Transmural healing is an emerging outcome assessed by intestinal ultrasonography (IUS), which allows frequent evaluation of CD.1,2 Real-world evidence on the effectiveness of current treatments to induce and maintain transmural response to inform treatment decisions is limited. The SUNRISE study aims to describe pts with CD treated with VDZ achieving a composite outcome of complete remission, and transmural response, utilizing IUS.

Methods
SUNRISE is an ongoing observational, prospective study (NCT05192863) being conducted across 10 sites in Canada, Israel and Italy. Adults with moderately to severely active CD, with a bowel wall thickness of &gt;3 mm based on IUS, and who newly initiated intravenous VDZ are eligible. Complete remission (defined as a composite endpoint of clinically corticosteroid-free [Harvey–Bradshaw Index score of &lt;5 points and no concomitant corticosteroids], biochemical [C-reactive protein and faecal calprotectin normalization] and transmural remission [assessed by IUS]), and transmural response after VDZ treatment are reported after induction with VDZ (Weeks 10/14) and every 6 months until Month 18 or early discontinuation. Methodological details are shown in the Figure.

Results
This interim analysis included 70 pts; median (interquartile range [IQR]) age was 50.0 (39.0–67.0) years, time since CD diagnosis was 4.0 (0.9–17.2) years and treatment duration (n=69) was 5.0 (3.2–6.1) months. At Month 6, the proportion of pts achieving complete remission, and transmural remission and response were 3/11 (27.3%), 9/28 (32.1%) and 12/28 (42.9%) pts, respectively; data at Weeks 10/14 are shown in the Table. Median (IQR) Short Inflammatory Bowel Disease Questionnaire total score was 4.3 (3.7–5.6) at baseline, 4.5 (3.4–5.3) at Week 10, 4.7 (3.9–5.6) at Week 14 and 5.0 (4.4–6.1) at Month 6. At Month 6, 10/21 pts (47.6%) ranked IUS as their preferred test over colonoscopy, magnetic resonance elastography and computed tomography enterography. Of 40 pts with available data at Month 6, 6 (15.0%) discontinued treatment, 5 (12.5%) switched to subcutaneous VDZ and 1 (2.5%) skipped ≥1 dose of VDZ. During the observation period, 2/70 pts (2.9%) had a CD-related hospitalization, and 1/70 pt (1.4%) each had a CD-related emergency room visit or CD-related surgery (fistula removal).

Conclusion
The SUNRISE study provides real-world evidence for the use of VDZ to achieve transmural healing in pts with CD and supports pt preference for IUS over other monitoring modalities. Additional follow-up data are required to confirm these findings.

References
1.Ilvemark J.F.K.F. et al. J Crohns Colitis 2022;16:554–80.
2.Turner D. et al. Gastroenterol 2021;160:1570–83.
P0815 Oral alpha 4 beta 7 (α4β7) integrin antagonist EA1080 (NSHO-101) demonstrates target engagement and α4β7 integrin receptor occupancy following once-daily administration in healthy volunteers
Authors: Feagan B G , Yazawa Y , Seki T , Watanabe E , Ohishi H , Ueo H , Saito C , Lorch U 
Published: January 2025

Abstract

Background
EA1080 (NSHO-101) is a selective, oral small molecule α4β7 integrin antagonist being advanced for the treatment of inflammatory bowel disease (IBD). EA1080 (NSHO-101) was safe and well tolerated and resulted in near complete inhibition of MAdCAM-1 binding to α4β7 integrin (receptor occupancy) on peripheral blood CD4+ T cells following twice-daily dosing with Formulation X in a healthy volunteer phase 1 study (DDW 2024: Su1789; NCT04223960). No effect on peripheral blood lymphocyte count was observed, confirming no specific engagement of α4β1 integrin. Here pharmacokinetics (PK) and pharmacodynamics (PD) results from a once-daily formulation are presented.

Methods
The PK and PD results from multiple ascending dose (MAD) cohorts with a formulation utilizing once-daily dosing were assessed in a healthy volunteer phase 1 study. Peripheral blood lymphocyte counts were assessed across the dosing period.

Results
Once-daily administration of EA1080 (NSHO-101) resulted in sustained, near-complete inhibition of MAdCAM-1 binding to α4β7 integrin on peripheral blood CD4+ T cells (≥95% receptor occupancy) across the dosing interval (24 hours). This correlated with plasma concentrations of active metabolite of EA1080 (EA1080-M) and approximated the level of receptor occupancy seen with twice-daily dosing with Formulation X. Plasma concentrations of EA1080-M reached steady-state levels within 3-4 days, and this correlated with maximal inhibition of MAdCAM-1 binding (receptor occupancy). No consistent trend in peripheral blood lymphocyte counts was observed across the dosing period.

Conclusion
These results demonstrate that once-daily oral administration of EA1080 (NSHO-101) results in near complete inhibition MAdCAM-1 binding to α4β7 integrin (≥95% receptor occupancy) across the dosing interval. No effect on peripheral blood lymphocyte counts was observed, confirming no specific engagement of α4β1. These results support continued development of a once-daily dosing formulation for future clinical studies.
P0816 Dietary habits of ulcerative colitis patients under follow-up in a Pediatric Inflammatory Bowel Disease Unit
Authors: Herrador Lopez M , Martín-Masot R , Sarbagilli C , Navas-López V M 
Published: January 2025

Abstract

Background
A Western dietary pattern characteristics was suggested to have a role in the pathogenesis of ulcerative colitis (UC). Poor dietary pattern can exacerbate the patients’ symptoms and lead to significant nutrient deficiencies. However, data regarding dietary habits and nutritional needs are scarce. Our study aimed to prospectively evaluate dietary intake and habits in peadiatric patients with UC at a Spanish tertiary hospital.

Methods
In this prospective observational study, peadiatric UC patients were followed up, during which their dietary habits were collected. Patients were asked to complete the KIDMED questionnaire for adherence to the Mediterranean diet (MD) and a 3-day food diary. The degree of food processing was assessed using the NOVA classification system, which classifies all food products into four main groups.

Results
A total of 47 patients were included, with a mean age of 11.9±3.3 years (57% female), and a median follow-up of 2.8±5.4 years. The mean caloric intake was 1919.07 ± 292.8 kcal, and 55.31% of patients did not cover their energy requeriments. Protein and saturated fat intake exceeded the recommended daily intake (RDI): mean protein intake was 2.13±0.8g/kg (239.06% of RDI), and saturated fatty acids was 31.65±7.9% of total fat. In contrast, fiber, calcium and iron intake were below recommendations: mean fiber was 13.44±2.9g (75.1±24.7% of RDI), calcium was 457.7±239.3mg (41.6±26.2% of RDI) and iron 8.3±3.4mg (75.3±37.2% of RDI). The average KIDMED score was 6.2 points, with only 15 patients (31.9%) presenting high adherence to the MD. Of the remaining patients, 26 (55.3%) needed to improve their diet quality, and 6 (12.7%) had very low diet quality. Regarding the NOVA classification, 7 patients (14.9%) consumed more than 40% of their total energy from ultra-processed foods (NOVA 4), while 23 (48.9%) had less than 40% of their energy intake coming from unprocessed or minimally processed foods (NOVA 1).

Conclusion
Our results highlight that a substantial proportion of pediatric UC patients have suboptimal dietary patterns, characterized by high intake of UPF and saturated fats, alongside low intake of fiber, calcium, and iron. These findings suggest a need for tailored follow-up with a specialized dietitian within the multidisciplinary care team. Further research is essential to clarify the impact of diet on UC.
P0820 Video-assisted anal fistula treatment (VAAFT) in Crohn´s perianal disease: a Brazilian single-center prospective cohort study
Authors: Gardere Camergo M , Vital Pinheiro Saito L , Natali Moraes P , Minatel Vidal de Negreiros L , Nunes Angelo S , Real Martinez C A , Oliveira Magro D , Saddy Rodrigues Coy C 
Published: January 2025

Abstract

Background
Perianal involvement is identified in one-third of patients with Crohn’s disease, including fistulas, fissures and skin tags. Perianal Crohn´s disease (PCD) is associated with decreased quality of life, due to significant physical and psychologic symptoms. Video-assisted anal fistula treatment [VAAFT] is a minimally invasive surgical technique for anal fistulas, accessing primary and secondary fistula tracks for drainage and fulguration of inflammatory tissue. Our study reports the use of VAAFT for management of PCD fistulas along with medical therapy, aiming to improve symptoms and promote healing.

Methods
A single-center prospective study was conducted in consecutive patients with symptomatic PCD fistulas submitted to VAAFT, from January 2020 to January 2024. The surgical procedure involved an perianal exam under analgesia and VAAFT for fistuloscopy and cauterization of fistula tracks, with setons installation and\or replacement in order to maintain postoperative drainage. The primary endpoint was completion of the ‘Perianal Disease Activity Index (PDAI)’ questionnaire at 8 weeks postoperatively. Secondary outcome measure was ´IBDQol´ questionnaire at 8 weeks postoperatively, postoperative complications and the 30-day re-operation rate.

Results
Thirty-nine patients underwent VAAFT procedure for PCD during the study period. In total, 34/39 patients [87%] provided PDAI data, demonstrating a statistically significant improvement in scores of discharge, pain and sexual activity scores. In total, 34/39 patients [87%] provided IBDQol data, demonstrating a statistically significant improvement. The only complication was sepsis in one female 28-year old patient at the immediate postoperative period, successfully managed with clinical treatment in intensive care unit. There was no re-operation in 30-day period.

Conclusion
Our study demonstrates the feasibility, safety and importantly an improvement in patient-reported outcomes of patients undergoing VAAFT for management of PCD fistulas. VAAFT reduced the symptoms of discharge and paiin patients with complex refractory PCD fistulas.
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

Abstract

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

Abstract

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&lt;0.001) following dietetic intervention. Similarly, IBD-DI scores improved by 3 points (95% CI 1.78, 4.22; p&lt;0.001), knowledge of what to eat improved by 37% (p&lt;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

Abstract

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 &lt; 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

Abstract

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 &gt;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