bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0634 Upadacitinib Effectiveness And Safety In Patients With Ulcerative Colitis: Data From A Real-World Study
Authors: Mocci MD FRCP G , Scaldaferri F , Napoltitano D , Pugliese D , Maconi G , Pica R , Savarino E , Costa F , Ceccarelli L , Marzo M , Elisei W , Lombardi G , Ribaldone D G , Bertani L , Rodino S , Orrù G , Bodini G , Pranzo G , Scarcelli A , Luppino I , Ferronato A , Spagnuolo R , Gravina A G , Pellegrino R , Vespere G , Allegretta L , Fanigliuolo L , Grossi L , Cortellini F , Piergallini S , Capone P , Gaiani F , Mucherino C , D’Ascoli B , Colucci R , Onidi F M , Usai Satta P , Picchio M , Papa A , Tursi A ,   IN-IBD (Italian Network of Inflammatory Bowel Disease)
Published: January 2025

Abstract

Background
Upadacitinib (UPA), a selective anti-JAK1, has obtained refundability from the Italian National Health System in July 2023 for its use in patients with Ulcerative Colitis (UC) refractory to other therapies, including anti-TNF-α, anti-integrins and ustekinumab. At present, no Italian data are available yet about its effectiveness and safety in Real World.

Methods
A retrospective assessment of clinical and endoscopic activity was performed according to the Mayo score. The primary endpoints were to evaluate the effectiveness and safety of UPA.

Results
We enrolled 186 patients with a median follow-up of 24 weeks weeks (M/F 105/76, median age 41). Clinical remission was achieved in 31% (57/186) and 70% (55/78, p&lt;0-05) patients at 8-week and 24-week follow-ups, respectively; clinical response was achieved in 103/186 (55%) and 68/78 (87%, p&lt;0.5) patients at 8-week and 24-week follow-ups, respectively. Adverse events occurred in 5 (2.6%) patients and severe in 1 (0.5%).

Conclusion
Our realworld data confirm that UPA is effective and safe in UC patients. It performs remarkably better when used as the first/second line of treatment.
P0636 Impact of obefazimod treatment on histologic and combined histologic and endoscopic outcomes in patients with moderately to severely active ulcerative colitis: results from the Phase 2b open-label maintenance study
Authors: Magro F , Peyrin-Biroulet L , Biedermann L , Sands B E , Danese S , Dulai P S , Dubinsky M , Tilg H , Siegmund B , Hisamatsu T , Shan K , Jacobstein D , Cataldi F , Rabbat C , Vermeire S 
Published: January 2025

Abstract

Background
Obefazimod is an investigational, oral, once-daily (QD), small molecule which enhances expression of microRNA-124 and demonstrated efficacy and safety in patients with moderately to severely active ulcerative colitis (UC) in a placebo-controlled, Phase 2b induction trial and the subsequent 96-week open-label maintenance (OLM) study [1, 2]. Here, we report proportions of patients that met endoscopic, histologic and combined histologic-endoscopic outcomes at the end of the induction trial (baseline of OLM), Weeks 48 (W48) and 96 (W96) of the OLM study.

Methods
Patients received obefazimod 25mg, 50mg or 100mg once daily (QD) or placebo during induction and could enter the optional 96-week OLM study irrespective of their clinical response to receive obefazimod 50mg QD. Rectal or sigmoidal biopsies were collected during endoscopy at OLM baseline, W48 and W96 to evaluate treatment effect on histopathology scores using the Geboes score. Endoscopic improvement (endoscopic sub-score ≤1), endoscopic remission (endoscopic sub-score = 0), histologic improvement (Geboes histologic score ≤3.1), histologic remission (Geboes histologic score &lt;2.0), histo-endoscopic mucosal improvement (HEMI, Geboes histologic score ≤ 3.1 and endoscopic improvement) and histo-endoscopic mucosal remission (HEMR, Geboes histologic score &lt;2.0 and endoscopic remission) were evaluated using as observed analysis (i.e. only patients with both endoscopic and histologic outcome for each endpoint) and non-responder imputation (NRI) for patients missing either endoscopy data and/or histology data.

Results
There were 217 patients that completed the induction trial and entered OLM. In a data-as-observed analysis, the proportions of patients achieving endoscopic improvement increased from 49% at OLM baseline to 73% at W48, and 78% at W96. The proportion of patients achieving histologic improvement rose from 59% at OLM baseline to 85% at W48, and 89% at W96; 39% achieved HEMI at OLM baseline, and increased to 69% at W48, and 74% at W96 (Table 1). Similar trends were observed for remission endpoints as well as in the NRI analysis.

Conclusion
In this Phase 2b OLM study, patients with moderately to severely active UC treated with obefazimod experienced clinically meaningful improvements in endoscopic, histologic, and combined histologic-endoscopic outcomes with proportions of patients meeting these endpoints consistently increasing from OLM baseline through W96. These data suggest sustained and progressive therapeutic benefits over time.

References
1. Vermeire S, et al. J Crohns Colitis. 2023; 17: 1689-16972.
2. Vermeire S, et al. The Lancet Gastroenterology & Hepatology. 2022; 7: 1024-1035.
P0637 Ebrasodebart (Ent001) First in Human trial in healthy volunteers: pharmacokinetic results and predicted therapeutic concentrations to preserve mucosal healing in patients with Ulcerative Colitis
Authors: Zangarini M , Marin V , Maucci R , Stabile M , Di Sanza C , Maestroni A , Amabile G , Nardini C , D’Addio F , Fiorina P , Olson L M , Canducci F , Porzio S 
Published: January 2025

Abstract

Background
Ebrasodebart (Ent001) is a human IgG4 monoclonal antibody that antagonizes the binding of IGFBP3 to the novel cell death receptor TMEM219, expressed on Intestinal Stem Cells (ISCs) and well conserved across human and animal species. Ebrasodebart is thus expected to inhibit TMEM219-mediated activation of Caspase-8 and the exaggerated apoptosis of ISCs observed in patients with Ulcerative Colitis (UC). Ebrasodebart is currently in clinical development as a novel first-in class investigational treatment in patients with UC. A FIH single ascending dose (SAD) study in healthy volunteers (HVs) was conducted to define the safety, tolerability and pharmacokinetics (PK) of ebrasodebart at the concentrations anticipated to be required to elicit pharmacological and therapeutic activity in patients.

Methods
Thirty (30) HVs were enrolled in the monocentric, randomized, double-blind, placebo-controlled SAD study, 29 subjects completed the study. In vitro and in vivo concentration-response preclinical experiments defined the pharmacologically active concentrations, measuring the inhibition of IGFBP3-induced Caspase-8 activation in human intestinal epithelial cell lines and organoids, and the exposure-response in DSS-induced chronic colitic mice, while modeling and simulation (M&S) predicted effective concentrations.

Results
After single intravenous (IV) doses of ebrasodebart in HVs, maximum exposure (Cmax) and systemic exposure (AUCinf) increased in an approximately dose proportional manner with a low intersubject variability at all dose levels (CV% &lt; 20% for Cmax and AUCinf). Geometric mean t1/2 was between 17 to 19 days at the predicted therapeutic doses. Ebrasodebart achieved a Cmax of 296 µg/mL and AUC0-inf of 37646 µg/mL*h well below the No Observed Adverse Effect Level (NOAEL) from the 26-week chronic toxicity study in monkeys, but significantly higher than the minimal pharmacologically active concentration in vitro. The concentrations achieved in the FIH trial were also higher than those that significantly reduced the Disease Activity Index and both histological and endoscopic scores in mice, exceeding M&S predictions for pharmacological effectiveness in patients.

Conclusion
These data indicate that ebrasodebart concentrations with predictable PK and expected therapeutic efficacy can be safely reached in humans, and remained significantly below the NOAEL in monkeys, suggesting a potential for a wide therapeutic window in patients. A multicentric Phase 1b, randomized, double-blind, placebo-controlled trial is ongoing to evaluate safety, tolerability, PK, immunogenicity and preliminary efficacy of multiple ascending doses of ebrasodebart in patients with moderately to severely active UC.
P0915 Real-life experience with Upadacitinib in Crohn’s disease (UPARECOL-CD Induction): A Colombian cohort
Authors: Parra Izquierdo L V , Frías-Ordoñez J , Barreto Perez J , Gil Parada F L , Otero-Regino W , Tovar Fierro G M , Florez-Sarmiento C 
Published: January 2025

Abstract

Background
In Latin America, clinical experience with Upadacitinib for CD in terms of effectiveness and safety is limited. In Colombia, CD is an orphan disease and in many cases is highly refractory to conventional treatments. The objective of this study is to describe the real-life experience in Colombian patients with CD treated with Upadacitinib.

Methods
Descriptive observational study, patients with CD treated with Upadacitinib in induction phase (45 mg orally once a day for 12 weeks) in different reference centers nationwide. The therapeutic response was evaluated in endoscopic and/or imaging, paraclinical and clinical terms (CDAI). Additionally, the frequency of adverse events (AE), steroid use and extraintestinal manifestations (EIM) were measured.

Results
10 patients, 5/10 (50%) female, mean age 43.15 years (SD; 22.7 range 14.2-21.3). Mean age at diagnosis of CD 37.7 (SD 23.15) years (range 6.9-67.5). Mean time between disease onset and start of Upadacitinib 3.33 (SD 8.17) years (range 0.1-15.9). Most patients had moderate to severe CD; 7/10 (70%) patients with ileocolonic disease and 3 (30%) with ileal disease. 5 patients with stricturing disease and 3 patients with active penetrating disease. All patients had previously failed tumor necrosis factor inhibitors, 8/10 (80%) had failed integrin alpha4 beta7 inhibitors (Vedolizumab). Six patients had EIM. Six patients had a history of surgery for CD. Additionally, 4/10 (40%) patients were using a steroid before starting Upadacitinib and 6/10 (60%) patients were using an immunomodulator. During the induction phase, 7/10 (70%) achieved clinical response, 2/10 (20%) clinical remission, and 5/10 (50%) paraclinical remission. 4/6 (66.6%) patients achieved improvement in imaging findings. All patients with EIM showed improvement of EIM. 2/5 (40%) patients showed improvement of perianal disease. Only one patient required surgery for CD. 3/4 (75%) were able to discontinue corticosteroid and 1/4 (25%) achieved steroid dose reduction. One patient required discontinuation of Upadacitinib, due to lack of response and severe sepsis. One patient reported acne after induction. No other AEs were reported.

Conclusion
Upadacitinib is an effective option for patients with CD with inflammatory, stenosing and penetrating phenotypes refractory to multiple treatments, suggesting a reduced requirement for surgical procedures. Long-term real-life studies are needed to determine whether there is persistence of response in maintenance.
P0920 Long term follow-up of patients with ulcerative colitis after suspension of infliximab for stable deep remission
Authors: Dussias N , Melotti L , Vanigli N , Calabrese C , Gionchetti P , Rizzello F 
Published: January 2025

Abstract

Background
Infliximab (IFX) is the first anti-TNF biologic drug approved for treating moderate to severe ulcerative colitis (UC). While IFX is effective in inducing mucosal healing and enhancing quality of life, concerns persist about the long-term safety and cost-effectiveness of extended immunosuppression. Current guidelines lack clarity on when to discontinue treatment after achieving stable deep remission. Moreover, existing literature is limited to studies characterised by small sample sizes and heterogenous criteria for defining remission. We aimed to evaluate the outcomes in UC patients who discontinued IFX after achieving stable deep remission, to identify predictors of relapse post-discontinuation, and to examine the clinical course in those who experienced a relapse.

Methods
In this single-center, retrospective, observational study, we analyzed UC patients at our tertiary IBD Referral Center who discontinued IFX due to sustained deep remission, defined as the combination of partial Mayo subscore ≤ 1 and endoscopic Mayo score = 0, and who had at least 1 year of follow-up post treatment withdrawal. We assessed the relapse rates at intervals of 6 months, 1 year, 2 years, and beyond 2 years post-IFX discontinuation. For patients who relapsed, we recorded the therapeutic strategy and its effectiveness, including the necessity for colectomy. We performed univariate and multivariate analyses to identify relapse predictors post-treatment suspension.

Results
From 2006 to 2022, 790 UC patients received IFX treatment at our center; 113 patients suspended IFX due to stable deep remission with at least 1 year of follow-up and were included in this study. Of these, 41.6% maintained remission over a median of 5.17 years. Flare rates were 14.2%, 23.9%, and 35.5% within 6, 12, and 24 months, respectively, with 58.4% experiencing a flare overall. Multivariate analysis showed that longer treatment duration reduced relapse risk (p=0.001), while steroid use during IFX treatment and early IFX initiation post-diagnosis increased relapse risk (p=0.004 and p=0.043, respectively). Most patients who relapsed were successfully managed medically either with a course of steroids, restarting IFX, or initiating a different type of biologic/small molecule, whereas the rate of colectomy was 7.1%.

Conclusion
This study is one of the largest to date with the longest follow-up that evaluates outcomes post-IFX discontinuation in UC patients in deep remission. Our findings suggest that withdrawal of IFX treatment can be considered in carefully selected cases. In patients who relapse after IFX suspension, medical treatment is often effective, and the rate of colectomy is low. Further studies are warranted to better identify ideal candidates for treatment withdrawal.
P0921 Management of anti-TNF inmunogenicity in inflamatory bowel disease: data from a tertiary care hospital
Authors: López Cardona J , Mesonero Gismero F , García de la Filia Molina I , Fernández Fernández C , Roy Ariño G , Gramage Caro T , Albillos Martínez A 
Published: January 2025

Abstract

Background
When anti-TNF immunogenic failure occurs, the appropriate approach is unclear, with options including drug intensification, adding an immunosuppressant, or switching the therapeutic target.

Methods
A retrospective study was conducted on inflammatory bowel disease patients receiving anti-TNF therapy at a tertiary center, with anti-drug antibodies detected between September 2017 and July 2024 using a drug-sensitive ELISA (PROMONITOR). The primary aim was to assess anti-TNF persistency after implementing a strategy to reverse immunogenicity. The secondary aim was to evaluate strategies for managing anti-TNF immunogenic failure and outcomes.

Results
TDM was performed on 495 patients (62.3% proactive strategy); 53 had positive antibodies. Infliximab (IFX) immunogenicity was 15%, while Adalimumab (ADA) was 5.4%, showing significant differences (p &lt; 0.05), Table 1. Antibody positivity occurred after a median of 9.92 months from anti-TNF start (IQR 6.8–16.3), with no differences between ADA and IFX.
After antibody detection, anti-TNF therapy was maintained in 23 patients (43.4%), switched to a second anti-TNF in 21 (39.6%), and changed to a different target in 7 (13.2%; 4 ustekinumab, 1 vedolizumab, 1 upadacitinib, 1 azathioprine). One patient underwent surgery, and treatment was discontinued in another. No significant differences in antibody titers were observed between patients who continued anti-TNF therapy and those who did not, Table 1.
In the maintenance group, dose intensification was performed in 5 (21.7%), immunosuppression was added in 6 (26%), and both measures were applied in 12 (52.1%). In 21 patients, a second-level determination was performed after a median of 24 weeks (IQR 18–74.7), with 65.2% (15/21) showing immunogenicity reversal, with no significant differences between the three strategies. Antibody titers or the strategy to reverse immunogenicity were not associated with first anti-TNF persistence during follow-up.
Figure 1 shows survival curves for second-line persistency among patients maintained on the same anti-TNF, those with a second-line anti-TNF, and those who switched to an alternative targeted therapy. Although switching to a second-line anti-TNF shows better outcomes, no significant differences were observed (p=0.25).

Conclusion
In patients with anti-TNF immunogenic failure, adding an immunosuppressant or increasing the dose can reverse immunogenicity, but few patients remain on anti-TNF therapy long-term. Additional studies are needed on the impact of antibody titers in treatment decisions. Switching to a second anti-TNF shows positive clinical outcomes.
P0929 Design and rationale for the phase 1c study evaluating the pharmacodynamic (PD) effects of vixarelimab in patients with Ulcerative Colitis (UC)
Authors: Neighbors M , Hains A , Rhee H , Tang F , Onabajo O , Quintanilla L , Eshghi S , Kulkarni P , Chatterjee S , Schroeder A , Garma H , Lear S , Hendricks A , Jha D , Mehandru S 
Published: January 2025

Abstract

Background
Vixarelimab, a selective oncostatin M receptor-beta (OSMRβ)-targeting, fully human monoclonal antibody, blocks OSM signaling and is hypothesized to target the inflammatory fibroblast-myeloid axis implicated in UC. An ongoing randomized, placebo-controlled Phase 2 MOONGLOW study (NCT06137183) is evaluating the efficacy and safety of vixarelimab in patients with UC. Here we report on the rationale and design of an open-label, single-arm Phase 1c study to provide deeper mechanistic insights regarding vixarelimab in patients with UC. The primary objective is to evaluate vixarelimab PD in the gut through assessment of the change in inflammatory fibroblast products from colonic tissue. Additional objectives include evaluation of receptor occupancy, pharmacokinetics, and safety.

Methods
The study will enroll ~24 patients to receive vixarelimab subcutaneously on two separate visits with a 6-week evaluation period and a subsequent safety follow-up (Figure 1). Patients will undergo endoscopy with biopsy collection from the colon and clinical assessments at screening/baseline and throughout the evaluation period. The timepoints of post-treatment assessments correspond to predicted steady state systemic drug exposures for the doses evaluated in the ongoing Phase 2 study. This enables PD evaluations in a Phase 1c population pharmacologically comparable to the Phase 2 study at timepoints earlier than possible in the Phase 2 study, whilst mitigating the confounding variables of disease resolution historically observed in UC studies after 12 weeks of placebo treatment.1

Results
To facilitate mechanistic assessments of vixarelimab we have established A) a novel method for the assessment of OSMRβ occupancy using fresh colonic tissues and B) a sample collection approach for snRNA-seq aimed to identify and characterize inflammatory fibroblasts that are anticipated to decrease upon vixarelimab engagement of OSMRβ (Figure 2). Using bulk RNA-sequencing, we have also identified a reduction in inflammatory fibroblasts by weeks 4 to 6 in patients with UC who respond to biologic therapy (GSE73661). These data provide evidence that changes in inflammatory fibroblasts may be identifiable earlier than the typical week 12 evaluation in IBD induction trials providing rationale for the early time points chosen for the present study.

Conclusion
Integrating OSMRβ occupancy assay and snRNA-seq informs on assessment of inflammatory fibroblasts in patients with UC, enabling mechanistic insights for first-in-class therapeutic targeting of the inflammatory fibroblast-myeloid cell axis by vixarelimab in UC.

References
1. Jairath et al. Cochrane Database Syst Rev. 2017;9:CD011572.
P0932 The Impact of Crohn’s Disease on Fertility in Chinese Women: A Comparative Study with the General Population
Authors: Peng X , Xu Z , Zhi M , Zhang M 
Published: January 2025

Abstract

Background
This study aims to clarify the uncertain impact of Crohn’s disease on fertility among Chinese female by comparing their fertility rates with those of the general female population.

Methods
From January 2012 to December 2022, Crohn’s disease patients at Sixth Affiliated Hospital of Sun Yat-sen University were identified through hospital records. Female patients aged 15 to 44 were included. Demographic and fertility data were collected through structured questionnaires. Comparative data for the general population aged 15 to 44 were obtained from the National Bureau of Statistics of China. Age-adjusted overall fertility rate and adjusted fertility rate ratio (AFRR) were calculated using poisson regression, along with fertility rate ratios for 5-year age groups stratified by disease onset, surgery, and perianal disease.

Results
A total of 564 valid questionnaires were collected. The overall fertility rate among females with Crohn’s disease was 43.41 live births per 1000 person-years (95%CI [39.30-48.11.]), significantly lower than the general population(52.80, 95%CI[52.72-52.97], AFRR 0.82, p&lt; 0.001). Pre-onset rates showed no significant difference, but there was a significantly decline post-onset(35.84, 95%CI[30.32-42.31], AFRR 0.55, 95%CI[0.46-0.65], p&lt;0.001). Fertility rates decreased in patients aged 20 to 29 post-onset. Those who underwent bowel surgery had reduced fertility rates post-surgery(31.44, 95%CI[21.05-92.49] vs 49.92, 95% CI [45.35-54.91], AFRR 0.63, 95% CI [0.45-0.89], p=0.008). Patients with perianal disease was 47% of that of the general population (25.05, 95% CI [8.94-40.97] vs. 48.61, 95% CI [43.57-52.97], AFRR 0.47, 95% CI [0.43-0.52], p&lt;0.001).

Conclusion
Female Crohn’s disease patients show lower fertility rates than the general population, particularly among those aged 20-29 age post-disease onset, with further reductions after surgery and perianal disease.
P0933 Symptoms improvement after VAAFT procedure in patients with perianal Crohn’s disease
Authors: Andreotti E , Todeschini A , Geccherle A , Variola A , Cracco N , Orlandi S , Barugola G 
Published: January 2025

Abstract

Background
Perianal fistulas may affect about 30% of patients with Crohn’s disease (CD). Management of perianal Crohn’s disease (pCD) is difficult due to the presence of complex and recurrent fistulae unlikely to heal spontaneously or after medical-surgical treatment. . Previous studies have shown how the use of Video-Assisted Anal Fistula Treatment (VAAFT) can lead to a benefit in terms of symptom control in patients with pCD. The aim of this study is to describe the outcome of VAAFT in terms of symptomatic improvement in patients affected by pCD.

Methods
A retrospective study was conducted in a single centre on CD patients with perianal fistulae undergoing VAAFT procedure from July 2021 to April 2024. According to the AGA classification, all perianal fistulae were "complex". The VAAFT procedures were performed with different technical aspect. Preoperatively and 8 weeks after the perianal surgery a questionnaire on symptoms was submitted to each patient. This questionnaire evaluated several items: pad usage per day and pain, discharge and daily activity limitation on a 0-6 point Likert scale.

Results
25 patients underwent 37 VAAFT procedures. Ten patients had &gt; 1 VAAFT. The median duration of pCD was 6 years. The majority of patients underwent previous anal fistula surgery and 13 patients were on biological therapy at the time the first VAAFT. 12 (48%) had multiple or secondary tracts; an additional 17 (68%) had an abscess and 3 (12%) horseshoe fistulae. Median values of pain score (5 vs 0, p&lt;0.001), discharge score (5 vs 2, p&lt;0.001), daily activity limitation score (4 vs 1, p&lt;0.001) and pads usage per day (4 vs 1, p&lt;0.001) significantly decrease after VAAFT procedure. Of these 25, 3 patients reach an improvement in symptoms after the second VAAFT procedure. No post-procedural complication were recorded.

Conclusion
VAAFT is a safe, repeatable and minimally invasive procedure that can provide a reduction of symptom burden in pCD patients, affecting their quality of life.