bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0808 Early Top-down treatment improves transmural remission rates in Crohn's disease - a risk-adjusted propensity score matched analysis
Authors: Fernandes S R , Rodrigues I B C , Da Silva Neves A , Saraiva S , Rita Gonçalves A , Valente A , Moura Santos P , Correia L , Cortez-Pinto H , Magro F ,   Grupo de Estudos de Doenças Inflamatórias do Intestino
Published: January 2025

Abstract

Background
top-down treatment with biologics has been associated with higher rates of endoscopic remission compared to step-up treatment in Crohn’s disease (CD). We evaluated the benefits of this strategy in respect to transmural remission.

Methods
case-cohort study including CD patients naïve to immunosuppressants and with endoscopic and radiologic evidence of active disease.
Rates of transmural remission were compared between patients receiving early top-down treatment (immediate start of biologics or within 6 months of immunomodulators) and conventional step-up treatment (start of biologics &gt; 6 months after immunomodulators). A propensity score matched analysis was performed adjusting for variables associated with disabling disease (age at diagnosis, disease duration, smoking, phenotype, perianal disease, extensive small bowel disease). Transmural remission was defined as combined endoscopic and radiologic remission. Endoscopic remission was defined as a SES-CD ≤ 3 (non-operated patients) or a Rutgeerts score &lt;i2 (operated patients). Radiologic remission was defined as a simplified Maria score ≤1.

Results
327 patients were included in the analysis, 52.3% receiving conventional step-up treatment and 47.7% early top-down treatment. Rates of transmural remission decreased from 40% to 14.3% in patients with 0 and 5 risk factors for disabling disease, respectively. Early top-down treatment resulted in higher rates of transmural remission (33.3% vs 18.1%, P= 0.002) with similar results in the propensity score matched analysis (34.9% vs 18.5, P= 0.002). In multivariate analysis, early top-down treatment increased the chances of obtaining transmural remission (OR 2.187 95%CI 1.270-3.665, P= 0.005).

Conclusion
Early top-down treatment with biologics improves the rates of transmural remission in CD. Risk factors for disabling disease influence the chances of obtaining transmural remission.
P0822 Comparative Effectiveness and Safety of Upadacitinib and Vedolizumab in Anti-TNF Experienced Patients with Ulcerative Colitis: A Retrospective Study
Authors: Sror N , Leibovitzh H , Hirsch A , Thurm T , Ron Y , Maharshak N , Cohen N A 
Published: January 2025

Abstract

Background
Upadacitinib (UPA) and vedolizumab (vedo) are approved for use in patients with moderate to severe ulcerative colitis (UC). Data comparing these therapies as second line in Anti-TNF experienced patients are limited yet important to aid in determining therapeutic positioning.

Methods
This was a retrospective study conducted between 2015-2024. Patients receiving vedo or UPA for at least 14 weeks following anti-TNF failure were included. Clinical response was defined as a decrease in the Partial Mayo Score by two or more points from baseline, and remission as a score less than two. Clinical response and remission rates at weeks 14 and 52 were compared between the two groups.

Results
Eighty-eight patients, 66 treated with vedo and 22 with UPA were included in this study. The mean ages of the vedo and UPA cohorts were 45.7 ±19 years, and 39.4 ± 12.8, respectively. Thirty-one males (46.9%) were treated with vedo, and nine (40.9%) with UPA. Patients treated with vedo had significantly higher rates of cardiovascular comorbidities (30.3% vs 0%, p&lt;0.001), a higher rate of never smokers (86.8% Vs 63.6%, p=0.018), and shorter disease duration (8.9 years Vs 13.2, p = 0.03). (Table 1). There was no significant difference in terms of clinical response or remission although there was a trend towards a higher likelihood of both in patients receiving UPA (clinical response: adjusted odds-ratio (aOR)=6.85, P=0.09, 95% confidence interval (CI):0.74-62; clinical remission: aOR=3.7, P=0.14, 95% CI: 0.6-21.6). There was a greater decrease in fecal calprotectin in patients receiving UPA during follow-up although this was not significant (mean change of 1,750 ± 2,284 Vs 771 ± 1,727, P=0.13). Patients treated with UPA were significantly more likely to experience adverse events (AE) (aOR 8.72, CI: 1-65, P=0.04) (Table 2). Two patients treated with vedo had treatment discontinuation, one due to pulmonary embolism, and the other by the patient’s request with no objective AE. In the UPA cohort, there were no major AE resulting in treatment discontinuation. One patient in the UPA cohort had mild cutaneous herpes which required a temporary pause in therapy. No patients were hospitalized during the treatment period.

Conclusion
Clinical effectiveness of UPA and vedo were comparable in anti-TNF experienced patients with UC although there was a trend towards greater clinical response, remission and biochemical improvement in patients receiving UPA. Patients receiving UPA experienced a significantly higher incidence of AE. These data suggest that decision making based on disease severity and co-morbidities can help guide positioning of these therapies.
P0824 Patient-Reported Outcomes in Chinese Patients with Inflammatory Bowel Disease treated with Vedolizumab: A subgroup analysis of second interim analysis of VALUE study
Authors: Gao X , Ge W , Yu J , Wang X , Feng X , Qian X , Gu L , Chen M 
Published: January 2025

Abstract

Background
Vedolizumab (VDZ), a gut-selective monoclonal antibody for α4β7 integrin, approved in China for treating inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD). Here, we assess the improvements in symptomatic relief and quality of life (QoL) by patient-reported outcomes (PROs) from the second interim analysis of VALUE study (NCT04872491).

Methods
VALUE study is a prospective, multicenter, single-arm observational study. Enrolled patients with UC/CD aged &gt;18 years, were treated with 300mg VDZ at week 0, 2, 6, and every 8 weeks until 54 weeks. This second interim subgroup analysis was conducted 2 years after the first subject enrolment (data cutoff: 21 Oct’ 2023), which assessed the QoL using partial Mayo score [a composite index of rectal bleeding sub-score (RBS) and stool frequency sub-score (SFS)]for the patients with UC, and abdominal pain sub-score (APS), loose stool frequency sub-score (LSFS) for pts with CD at baseline, days 3, 7 and 14. IBD questionnaires (IBDQ), EuroQol - 5 Dimensions – 5 Levels index (EQ-5D-5L), EuroQol – Visual Analogue Scale (VAS) scores from baseline to week 14. Descriptive statistics summarized the effectiveness.

Results
Of 500 pts (UC: 409, CD: 91), 61.60% were males (61.60%) with a mean partial Mayo score of 5.2±2.09 and Harvey-Bradshaw Index (HBI) score of 5.6±3.35 in pts with UC and CD, respectively. After the treatment with VDZ in 315 pts with UC, the RBS and SFS score decreased(Figure 1), 34.92% (110 pts) achieved RBS=0 and SFS≤1 at baseline, which further increased to 51.69% (168 pts) and 64.19% (190 pts) by in day 7 and 14 respectively. Compared to baseline, the RBS = 0 and SFS≤1 scores improved by 30% (34.92% to 64.19%) at day 14, demonstrating the rapid onset effect of VDZ (Table 1A). In the pts with UC, mean IBDQ, EQ-5D-5L and EQ-VAS scores showed improvement from baseline (148.3 ±37.88, 0.890±0.157 and 76.1±15.56, respectively) to week 14 (186.7±26.30, 0.948±0.105 and 85.5±11.74, respectively) (Table 1B).
The mean pro scores from baseline to day 14 in patients CD are presented in Figure 1. APS≤1 and LSFS≤3 scores in pts with CD treated with VDZ improved from 75% at baseline to 78.08%, 82.19% and 85.51% on days 3, 7 and 14, respectively (Table 1A). Improvement in IBDQ scores was observed from baseline (161.8±37.53) until week 14 (177.4±24.43). Similarly, the mean EQ-5D-5L and EQ-VAS scores from baseline (0.908±0.1126 and 77.2±15.68) to week 14 (0.942±0.0586 and 82.4±10.98) were also improved in CD pts (Table 1B) signifying improved QoL.

Conclusion
VDZ treatment was associated with significant symptomatic relief and improved quality of life in Chinese patients with IBD.
P0829 ‘Temporary’ faecal diversion in refractory Crohn’s Disease: too good to be true? A retrospective, single centre analysis
Authors: Alliet B , Bislenghi G , Vermeire S , Guedelha Sabino J P , Ferrante M , D’Hoore A , Verstockt B 
Published: January 2025

Abstract

Background
Refractory Crohn’s disease (CD) is associated with high morbidity and significantly impaired quality of life. Similarly, perianal fistulising disease is a debilitating condition for a subset of CD patients. As the faecal stream is believed to play an important role in disease pathophysiology, a diverting (ileo)stomy, is sometimes considered as a therapeutic option in patients with extensive colitis and/or refractory anal disease. Long-term outcomes of temporary faecal diversion are limited. We aimed to assess the long-term effect of faecal diversion in CD patients with refractory colon and/or perianal disease, and identify factors associated with successful ostomy reversal.

Methods
We conducted a single centre, retrospective observational cohort study in a large IBD referral centre. We included all CD patients who underwent an ileostomy as a temporary measure for managing their refractory disease between 2019 and 2023, enabling at least 12 months follow-up.
We evaluated the clinical impact of faecal diversion, and explored the rate of (successful) restoration of transit. Clinical improvement was defined as significant symptomatic improvement, according to physician global assessment. Resolution of perianal disease was defined as the absence of perianal fistula at the time of the multidisciplinary assessment for transit restoration.

Results
A total of 42 patients, with a median age of 31.5 (interquartile range, IQR 24.2–40.9) and median disease duration of 12.4 (IQR 5.8-18.4) years at time of diversion were included. Patients were followed up for a median of 46.5 (IQR 30.2-67.5) months after ileostomy. Indication for faecal diversion was refractory colitis in 26.2% (n=11), and/or severe perianal disease in 73.8% (n=31). Advanced IBD therapy was restarted in 78.6% (n=33) of patients following diversion.
Faecal diversion resulted in clinical improvement in 57.1% of patients (n=24), of whom 70.8% received advanced therapy (n=17/24), and resolution of perianal disease in 35.5% (n=11/31). A total of 14 patients (33.3%), of whom 7 with a perianal phenotype, were proposed for restoration of transit by the multidisciplinary team. Ultimately, in 9/14 patients, including 4 with perianal disease, the ileostomy was reverted with a persistent bowel continuity of 89.9% after 19.0 (IQR 10.7-27.2) months of follow-up.

Conclusion
Temporary faecal diversion in patients with severe refractory Crohn’s colitis and/or anal disease resulted in significant clinical improvement in almost two thirds of patients, but is often a bridge to a permanent stoma as stoma reversal could only be considered in one third of patients. In these selected cases where the transit was restored, persistent bowel continuity was high.
P0830 Use of FK-adalimumab biosimilar (MSB 11022) in context of biologic switch in Inflammatory Bowel Diseases : 6 months data of the real-world IDEA study
Authors: Peyrin-Biroulet L , Bouhnik Y , Hebuterne X , Fumery M , Taxonera C , Gutierrez-Casbas A , Howaldt S , Stein J , Lindsay J , Monnet J , Simoes E , Dolfi F 
Published: January 2025

Abstract

Background
Biosimilars offer similar efficacy and safety when compared to their originators, thereby enhancing patient access to more affordable treatments. FK-adalimumab (FK-ada) is an adalimumab biosimilar approved for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC). FK-ada development included 1,234 subjects treated up to 52 weeks (total 420 patients-year). Since first approval, there have been no unexpected safety signals despite more than 115,000 patient-years of exposure. IDEA is an ongoing real-world study aimed to assess persistence with FK-ada and develop a predictive model of persistence at 12 months. In this study, adult patients with IBD who switched from adalimumab originator or another adalimumab biosimilar to FK-ada are followed up to one year.

Methods
Data collected include patient characteristics, reasons for treatment switch, clinical status at each follow-up visit including disease activity scores (Harvey-Bradshaw Index (HBI) and Montreal classification), and faecal calprotectin results. Adult patients with either CD or UC were included, those receiving treatment outside of routine clinical care were excluded. Data are presented using descriptive statistics and a logistic regression model will be employed to identify potential predictive factors at 12 months. We present here the baseline characteristics of IBD patients, and the 6 months intermediate results.

Results
A total of 136 IBD patients (CD: 112, UC: 24) were recruited across France, Germany and Spain, 57% being males, median age of 43 years and median BMI of 25.2 kg/m2. At the time of switch 97.3% of patients with CD and 87.5% with UC were in clinical remission or had mild to moderate disease activity. 54.4% of patients switched to FK-ada from originator, and 45.6% from another biosimilar, with most switches occurring for administrative reasons. A total of 103 IBD patients (CD: 87, UC: 16) completed the 6 months visit. Patients and disease status are summarized in Table 1. The persistence rate of FK-ada at 6 months was 76.4% (CD: 79%, UC: 65.2%). Most permanent treatment discontinuations occurred around 3 months after switch (median 3.6 months), primarily due to adverse events. Since the start of the study 46 patients (34%) experienced at least one adverse event (AE); 16 (12%) had at least one moderate to severe AE and 30 (22%) had AE(s) attributable to FK-ada.

Conclusion
6 months after the switch, FK-ada persistence rate was 76,4%. The majority of patients were still in remission or experiencing mild to moderate disease activity. Treatment and tolerance data from the study completion (52-week) will be critical for identifying predictive factors influencing drug persistence after the switch.
P0835 AI-guided generation and development of HXN-1001, a highly potent and half-life extended anti-TL1A antibody
Authors: Huang J , Ran H , Li S , Su C , Chen C , Liu D , Pan Y , Xu X , Chen X , Fei K , Tian J , Wang M , Tian L , Peng J , Zhu Z 
Published: January 2025

Abstract

Background
TL1A, a member of the TNF family, is genetically associated with several human autoimmune diseases, including IBD, psoriasis, and RA. TL1A-blocking antibodies have demonstrated clinical efficacy in patients with UC and CD. HXN-1001 is a novel humanized anti-TL1A antibody with strong blocking activity and extended in vivo half-life.

Methods
Affinity for soluble TL1A was assessed using SPR, while binding to membrane TL1A was measured with flow cytometry. The activity of HXN-1001 was validated through various in vitro experiments, including blocking TL1A binding to DR3-overexpressing cells, TL1A-induced TF-1 apoptosis, DR3-NFκB-Luc reporter assays, and IFN-γ release from primary T cells. In vivo efficacy was demonstrated in DSS-induced colitis and IMQ-induced psoriasis models using hTL1A, hTL1A/hα4β7, or hTL1A/hIL23 transgenic mice. The in vivo half-life was studied in hFcRn transgenic mice and rhesus monkeys.

Results
HXN-1001 is a humanized antibody that binds to TL1A via unique epitopes, exhibiting sub-nanomolar affinity for both TL1A trimer and monomer. It shows significantly stronger binding to TL1A-overexpressing cells compared to MK-7240 and RVT-3101. HXN-1001 effectively inhibits TL1A-induced NF-κB activity, apoptosis of TF-1 cells, and IFN-γ secretion in human primary T cells, with superior potency to both RVT-3101 and MK-7240. In a DSS-induced colitis model in transgenic mice, HXN-1001 demonstrated superior anti-inflammatory effects compared to RVT-3101, MK-7240, and the α4β7 antibody Vedolizumab. In an IMQ-induced psoriasis model, HXN-1001 exhibited better therapeutic effects than the marketed anti-IL-23 monoclonal antibody Risankizumab. The in vivo half-life of HXN-1001 is approximately 18 days in Tg32 hFcRn-transgenic mice and 23 days in Rhesus monkeys, supporting a clinical dosing frequency of at least every 8 to 12 weeks or even longer.

Conclusion
HXN-1001 is a next-generation antibody targeting TL1A, offering significant advantages in efficacy and in vivo half-life. It has strong potential to enhance clinical efficacy and dosing convenience. HXN-1001 is anticipated to enter clinical development in Q2 2025.
P0838 The clinical outcomes of Inflammatory Bowel Disease after liver transplantation for primary sclerosing cholangitis: a systematic review and meta-analysis
Authors: Zhou J , Sneek D , Hansen B , den Hoed C , de Jong M , Pan Q , van der Meer A J , Li P , de Vries A C 
Published: January 2025

Abstract

Background
The clinical course of inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC) after liver transplantation (LT) varies significantly across studies. This study aims to provide a comprehensive estimation of incidence rates (IR) for colorectal cancer (CRC) or high-grade dysplasia, bowel surgery, IBD exacerbation, and newly diagnosed IBD in PSC-IBD patients post-LT.

Methods
Online databases were searched from inception till January 2024 for studies reporting on patients who underwent LT for PSC with IBD diagnosed either before or after LT. The pooled IR were calculated with the "meta" package (R Studio [V.4.2.764] ) using a random effects model.

Results
Of 5,324 studies initially identified, 97 underwent full-text review, and 34 retrospective cohort studies were included in the meta-analysis. These cohorts encompassed 3,672 patients with LT for PSC, of whom 63% had concomitant IBD. The mean follow-up period across studies ranged widely from 2.46 years to 17.3 years.
A pooled analysis of 21 studies reporting on colorectal neoplasia revealed an overall IR of CRC or high-grade dysplasia post-liver transplantation of 6.7 cases per 1,000 person-years (95% CI 4.3-9.0) (Figure 1A). Across 18 studies, 17.8% (n=195/1094) patients with concomitant IBD at the time of LT experienced clinical exacerbation, defined as worsening of IBD symptoms, increased inflammatory activity at endoscopy, or required optimization of IBD treatment post-transplantation. The pooled IR of clinical exacerbation was 34.1 cases per 1,000 person-years (95% CI 22.7-45.5), though heterogeneity was high (I² = 76%). Notably, meta-regression revealed a decline in IR of clinical exacerbation over time exclusively within European countries, with no observed change elsewhere. Additionally, 16 studies reported on newly diagnosed IBD in PSC patients without pre-existing IBD at LT, with pooled IR of 12.6 cases per 1,000 person-years (95% CI 9.7-15.5) (Figure 1B). The overall bowel surgery rate post-LT was 20.2 cases (95% CI 16.9-23.4) per 1,000 person-years within 23 studies. More specifically, pooled colectomy rates for neoplasia and therapy refractory IBD were 10.5 cases (95% CI 6.7-14.2) in 16 studies, and 13.8 cases (95% CI 9.4-18.3) per 1,000 person-years in 10 studies, respectively.

Conclusion
This meta-analysis provides a thorough assessment of IBD outcomes in PSC-IBD patients following liver transplantation, highlighting the considerable incidence rates of colorectal neoplasia and newly diagnosed IBD. Close clinical follow-up and regular endoscopic surveillance remain essential in PSC patients post-LT.
P0844 Real-world effectiveness of vedolizumab in managing refractory pouchitis: a multicenter study on intravenous to subcutaneous transition
Authors: Gimeno-Pitarch L , Minguez A , Cespedes E , Ferreiro-Iglesias R , Martín-Arranz M D , Sicilia B , Lorca I , Huguet J M , Mesonero F , Vicente R , Nos P , Iborra M 
Published: January 2025

Abstract

Background
Chronic refractory pouchitis (RP) is a complication of ileal pouch-anal anastomosis (IPAA). Vedolizumab (VDZ) has been used in RP management, but real-world data on its effectiveness are limited. Additionally, information on switching from intravenous (IV) to subcutaneous (SC) VDZ in this context is scarce.

Aims
To evaluate the efficacy and safety of VDZ in RP treatment in a real-world clinical setting, to assess outcomes following a transition from IV to SC VDZ, and to compare treatment persistence and safety between IV and SC administration.

Methods
A multicenter Spanish study was conducted in patients with RP receiving VDZ for active pouchitis. Clinical outcomes were evaluated using the modified Pouch Disease Activity Index (mPDAI), and biomarkers such as faecal calprotectin (FC), C-reactive protein (CRP), and VDZ serum levels were monitored over one year. Patients who transitioned from IV to SC VDZ were assessed post-switch.

Results
A total of 47 patients were included (31 (66%) male; median age 51 [43, 64] years). Of these, 25 (53%) switched from IV to SC administration. Baseline characteristics are shown in Figure 1.
Significant reductions in mPDAI scores were observed with IV VDZ, from 5 (3-7) at baseline to 3 (2-5), 3 (2-5), (2-5.8) at weeks (W) 12, 24 and 52 respectively (p&lt;0.05). FC decreased significantly over time, from 443 µg/g (213, 746) to 329 µg/g (145-701), 193 µg/g (91-412) and 178 µg/g (101-640) at W12, 24 and 52, respectively (p&lt;0.05), although no significant changes were observed in CRP levels. VDZ serum levels were 16,9 μg/dl (10.3-25.7), 12 μg/dl (7.3-23), 9 μg/dl (6.7-13.9) at W12, 24 and 52 respectively. After switching from IV to SC VDZ, there were no significant differences in terms of mPDAI, FC and CRP at W12 and W24. However, a significant decrease in mPAI (p=0.04) and FC levels (p=0.038) was observed at W52. FC levels also dropped significantly from 550 µg/g (145-1163) pre-swich to 264 µg/g (52-989), 129 (101-448) and 62 (31-211) at W12, 24 and 52, respectively. Notably, SC VDZ serum levels increased significantly, from 8.5 μg/dl (7.2-14) at time of switch to 22.7 μg/dl (21-27.3), 19.6 μg/dl (16.5-21), 21.6 μg/dl (17-26.2) over time. Fewer prior advanced therapies correlated with better outcomes, whereas use of corticosteroids and immunosuppressants at baseline did not. VDZ persistence was high (Figure 2) and adverse event rates were similar for IV and SC VDZ (8.5% and 12%, respectively).

Conclusion
VDZ was effective in achieving clinical and biological remission in patients with RP following IPAA for ulcerative colitis, particularly with early intervention. Switching from IV to SC VDZ effectively sustained long-term remission, demonstrating safety and persistence in routine clinical practice.