bluuebunny/crossref_metadata_2025 huggingface dataset:
P0438 Altered Visceral Sensitivity in patients with Ulcerative Colitis in remission
Authors: Trikola A , Mylonas I , Gerasimos S , Viazis N
Published: January 2025

Background

Ulcerative colitis (UC) in remission is commonly associated with residual symptoms, despite adequate inflammatory control. Distinguishing between inflammatory and non-inflammatory causes is essential, in order to target therapy and avoid any unnecessary treatment escalation. Once mucosal inflammation has been excluded through endoscopic evaluation, high resolution anorectal manometry (HRAM) along with sensory testing could help symptom assessment. The aim on this study is to explore whether established physiologic diagnostic modalities such as HRAM could add value in investigation of patients with UC in remission.

Methods

Patients with confirmed UC in remission (after proper endoscopic assessment) were evaluated with Visceral Sensitivity Index (VSI, 15 items, ranging 0-75). They subsequently underwent HRAM with a solid-state catheter followed by the rectal sensory test by a gradual rectal distention according to the IAPWG Protocol, aiming to access rectal physiology and sensory perception.

Results

A total of 32 eligible adult patients (43% females, mean age 40,8 y.o.) were enrolled. Internal consistency for VSI was excellent (Cronbach’s alpha=0.933). Total mean VSI scores were 43.15 (26.11-60.19). An increased VSI score was reported in 12/37 (37.5%) of patients, whereas 20/32 (62.5%) of patients ranged low. Patients with increased total VSI scored significantly worse in bloating and abdominal distention, anxiety when going to new restaurants and worry, avoiding new foods, belief in a serious illness indication, a frightening abdominal discomfort and vigilance while no significant differences were found in mean rectal pressures and outcomes of balloon inflation (table 1).

Conclusion

Although a 37% of patients with UC in endoscopic remission score high in VSI, rectal pressures and perception as observed by the HRAM and ballon distention test are non-significant. VSI displays excellent consistency when evaluating patients with UC.
P0442 Prevalence and Impact of E-cigarettes on Disease Outcomes in Patients with Inflammatory Bowel Disease
Authors: Almuhaya H , Alashkar R , Alsebaai D , Albadawi N , Almutairdi A , Attamimi M , Desai S , Al-Bawardy B
Published: January 2025

Background

Electronic cigarettes (EC) have gained popularity as an alternative to traditional cigarette smoking. The harms of traditional cigarette smoking in Crohn’s disease (CD) are well established, but it is unclear if EC have similar harmful effects. Our aim was to determine the prevalence, predictors and impact of EC on clinical outcomes in patients with IBD.

Methods

This a cross-sectional study of a prospectively maintained single-center IBD registry from September 1st 2023-September 30th, 2024. The study included all patients aged 14-years and older who had a confirmed diagnosis of IBD including CD, ulcerative colitis (UC), IBD-unclassified (IBD-U), excluding those with pouchitis. The Primary outcomes were to determine the prevalence and predictors of EC use among patients diagnosed with IBD. The secondary outcomes assessed the impact of EC on clinical outcomes in IBD patients including the need for surgical intervention, CD progression (perianal disease, stricturing or penetrating complications), need for > 2 advanced therapies and composite outcome (intestinal surgery, disease progression, > 2 advanced therapies).

Results

A total of 412 patients were enrolled in the study (mean age 33 ± 13 years; 68% with CD) and 55% were male. Overall, 25% (n=102) of the cohort had traditional cigarette smoking history. EC use prevalence among IBD patients was 10.2% (n=42) (6.6% current, 3.6% previous users). Compared to non-users, EC-previous/current users were more likely to be male and have and have history of traditional cigarette smoking (Table 1). The prevalence of EC use was similar between patients with and without a history of intestinal surgery (10% for both, p > 0.9), with no significant differences noted in CD (p = 0.4) or UC (p = 0.5) subgroups. In CD, the prevalence of EC use was similar in patients with and without stricturing disease (8.9% vs. 13%; p=0.3), and perianal disease (13% vs. 11%; p=0.7). For penetrating disease, EC use was 7.8%, compared to 16% in those without penetrating disease (p=0.06). No difference in EC use was found in those patients who required > 2 advanced therapies (10%; n=4) vs. those who required ≤ 2 advanced therapies (10%; n=38) (p > 0.9). EC use was noted in 11% (n=29) in patients who developed the composite outcome vs. 8.2% (n=13) in those who did not (p=0.3).

Conclusion

Up to 10% of IBD patients reported EC use, which was associated with male sex and history of traditional cigarette smoking. In our cohort, no association between EC use and unfavourable clinical outcomes was noted but larger studies with longer follow up duration are needed to further elucidate the impact of EC use on clinical outcomes in IBD.
P0446 Increased risk of venous thromboembolism post hospital discharge in patients with Inflammatory Bowel Disease: a systematic review and meta-analysis
Authors: Subhaharan D , Zaka A , Mridha N , Haig A , Mohsen W , Kakkadasam Ramaswamy P
Published: January 2025

Background

Inflammatory bowel disease (IBD) increases the risk of venous thromboembolism (VTE). During acute hospitalisation, the risk increases up to six-fold, but is mitigated with pharmacological VTE prophylaxis. The European Crohn’s Colitis Organisation (ECCO) recommends extended prophylaxis for atleast 3 weeks for IBD patients undergoing major surgery. However, it is currently unknown whether this also applies for non-surgical hospitalisations for IBD patients. We performed an updated systematic review and meta-analysis to evaluate this risk. The primary outcome was evaluating the risk of post-hospitalisation VTE within 30 days after an IBD-related surgical or non-surgical hospitalisation.

Methods

PubMed, MEDLINE, EMBASE, CENTRAL and Web of Science was searched up until 1st June 2024 for observational cohort studies evaluating rates of VTE in IBD hospitalisations. Odds ratios were calculated using a random-effects model. Subgroup and sensitivity analysis were conducted in order to explore sources of heterogeneity.

Results

Seven eligible studies were included (973,267 IBD patients). 52.9% were female and mean age was 45.3 +/- 3.2 years. Average follow up was 43.2 +/- 5.6 months. Patients with IBD were associated with an increased risk of VTE within 30 days post-discharge in the adjusted analysis (OR 1.58; 95% CI 1.41-1.78) with moderate heterogeneity observed (I² = 67%, p = 0.005). Subgroup analysis based on hospitalisation type (surgical vs. non-surgical) revealed an increased risk amongst surgical hospitalisation for post discharge VTE (OR 1.34; 95% CI 1.09–1.64) with moderate heterogeneity (I² = 35%, p = 0.21). In contrast, non-surgical hospitalisation demonstrated a higher risk of post-discharge VTE (OR 1.70; 95% CI 1.52–1.90) with no significant heterogeneity (I² = 0%, p = 0.37). The overall effect size across both subgroups suggested a significant association between IBD and post-discharge VTE, with an odds ratio of 1.61 (95% CI 1.46–1.78), and moderate heterogeneity (I² = 45%, p = 0.10).

Conclusion

There is an independently increased risk of VTE within 30 days of a flare of IBD in both surgical and non-surgical hospitalisations. Extended VTE prophylaxis for all hospitalisations should be considered. Further prospective studies are required to identify specific patient risks.
P0545 Risk of rapidly progressive disease course in patients with pediatric-onset ulcerative colitis
Authors: D’Arcangelo G , Raso T , Ammattatelli F , Distante M , Zucconi F , Rotulo S , Aloi M
Published: January 2025

Background

Ulcerative colitis (UC) disease course is unpredictable at diagnosis and its management is still based on a “onesize-fits-all” approach. We aimed to investigate predictive factors of a rapidly progressive course in pediatric UC.

Methods

Retrospective case-control study conducted at Pediatric Gastroenterology Unit of Umberto I Hospital in Rome. We included newly diagnosed UC patients aged < 18 years, with a minimum follow-up of 24 months. Demographic and clinical data, laboratory, endoscopic and histologic findings at diagnosis were collected and compared between patients with indolent UC and those with a rapidly progressive (RP) course, defined if they experienced one of the following within the first 24 months after diagnosis: acute severe colitis under antiTNFα unresponsive to IV steroids, need for colectomy and need for second-line biologics or advanced small molecules with at least two different mechanisms of action1.

Results

One hundred and forty-two children were included, 61 (43 %) with a RP course and 81 (57 %) with an indolent course of disease. RP children had higher age (11.3 ± 4.2 vs 9 ± 4, p=0.0002) and a higher PUCAI (50 ± 13 vs 40.4 ± 12, p<0.0001) at diagnosis then those with indolent course. Hemoglobin was lower in RP group (11.6 ± 1.8 vs 12.4 ± 1.2 g/dL, p=0.001). RP children had higher rate of cecal patch at endoscopy (19% vs 2% p=0.001) and lower rate of sclerosing cholangitis (0 vs 8%, p=0.01). Endoscopic activity was more severe in RP compared to indolent patients as shown by the higher rate of Mayo 3 score (18% vs 2%, p=0.002) and median UCEIS (3.9 ± 1 vs 3.3 ± 0.9, p=0.001). The rate of severe histologic activity as graded by the local pathologist was higher in RP children (18% vs 1 %, p=0.004). The presence of a cecal patch at endoscopy was the only independent predictor for a rapidly progressive disease at the multivariate logistic regression analysis [OR 9.2 (95% CI 1.9-67.1), p=0.0009].

Conclusion

Children with a RP course seem to present with older age and a more clinically and endoscopically severe disease. However, only the endoscopic finding of a cecal patch emerged as an independent predictor of this course. These findings warrant confirmation in larger prospective cohorts to support a future personalized approach to UC.

References

1.Parigi TL, D’Amico F, Abreu MT, Dignass A, Dotan I, Magro F, Griffiths AM, Jairath V, Iacucci M, Mantzaris GJ, O’Morain C, Reinisch W, Sachar DB, Turner D, Yamamoto T, Rubin DT, Peyrin-Biroulet L, Ghosh S, Danese S. Difficult-to-treat inflammatory bowel disease: results from an international consensus meeting. Lancet Gastroenterol Hepatol. 2023 Sep;8(9):853-859.
P0549 Colombian Observer Inter-agreement in intestinal Ultrasound for ulcerative Colitis (COI-UC)
Authors: Parra Izquierdo L V , Ernest Suárez K , Argollo M , Frías-Ordoñez J , Orduz G , Ibañez E , Vargas M , Cubillos S , Verstockt B
Published: January 2025

Background

Intestinal ultrasound (IUS) is a non-invasive and effective tool for assessing intestinal inflammation in ulcerative colitis (UC) patients. Inter-observer agreement (IOA) in IUS for UC is crucial for accurate disease monitoring, particularly in countries and centers just implementing and educating on IUS, such as Colombia. Therefore, we conducted a study to assess the reliability of IUS in UC by comparing two Colombian gastroenterologists who performed prior at least 40 intestinal ultrasounds.

Methods

Thirty-seven patients with both clinically (in)active UC were included. Two gastroenterologists scanned all patients, assessing key IUS parameters, including bowel wall thickness (BWT), colour Doppler signal (CDS), loss of bowel wall stratification (BWS), presence or absence of mesenteric fat proliferation (i-fat) and lymph nodes. Statistical methods such as Cohen’s kappa or intraclass correlation coefficients (ICCs) were used to quantify agreement levels between both observers.

Results

Inter-observer agreement in BWT was analyzed per colonic segment and a moderate ICC average was found (0.746). However, for the most affected segment, the ICC was excellent (k=0.967), as was the agreement in calculating the Milan ultrasound score (MUC) score (k=0.981), the modified Limberg score (k=0.94) and CDS (k=0.94). Loss of BWS had a good agreement (k=0.83), while the agreement on the presence of lymph nodes and i-fat was moderate (k=0.53) and low (k=0.31), respectively.

Conclusion

Establishing a solid IOA with IUS for UC patients is vital for enhancing diagnostic accuracy and disease monitoring. Standardized acquisition and assessment of UC utilizing IUS with established reliability is important to expand the use of IUS in developing countries where this tool may be more cost-effective. Our results show a good to excellent IOA in this first Colombian initiative to implement IUS in UC. Further educational initiatives and improved standardization could further improve agreement among practitioners.
P0557 Multiomics analysis identifies key pathways associated with severe disease course in children with IBD: a prospective study
Authors: Azulay A , Talmor Y , Borenstein E , Focht G , Maslov T , Yogev D , Ledder O , Lev-Tzion R , Orlanski Meyer E , Assa A , Turner D
Published: January 2025

Background

Identifying biological pathways that are associated with poor disease course in IBD may improve early risk stratification and guide targeted therapeutic approaches. We therefore aimed to integrate multiomics data determined at disease onset to explore pathways associated with disease course in pediatric IBD, focusing on both microbial and host-derived signals.

Methods

Children with IBD were enrolled at disease onset and followed prospectively for18 months. Samples for whole exome sequencing (WES), serum metabolomics, stool metabolomics, and microbiome were analyzed using MaAsLin2 for differential expression and Random Forest for outcome prediction for single-omic. A late integration approach with Support Vector Machine was applied for multi-omics prediction. Severe outcome was defined as steroid-dependency, early or multiple biologics, or IBD-related hospitalizations/surgeries. Pathway enrichment analyses for each omic were assessed using Fisher’s exact test and odd ratio (OR) was calculated to asses the enrichment magnitude.

Results

Altogether, 182 children were enrolled (123 with CD (28% severe course) and 59 UC (39% severe course). Several pathways were differentially enriched in the severe group (Figure 1). Shared pathways across CD and UC included AGE-RAGE signaling, implicated in oxidative stress and inflammation (OR=36 [95%CI 3-459] in CD and OR=92 [7-1121] in UC), and choline metabolism in cancer, associated with lipid signaling, inflammation, and fibrosis (OR=37 [95%CI 4-382] and OR=66 [3-475]). CD-specific pathways included sphingolipid metabolism (OR=30 [95%CI 2-393]), linked to barrier dysfunction and chronic inflammation, glycerolipid metabolism (OR=11 [95%CI 1-160]), and fat digestion and absorption (OR=16 [95%CI 3-167]), highlighting disruptions in nutrient absorption and inflammation. UC-specific pathways included pathways in cancer (OR=23 [95%CI 3-263]), reflecting tissue remodeling and neoplasia risk, inflammatory regulation of TRP channels (OR=14 [95%CI 1-143]), contributing to colonic inflammation, sensory perception and purine metabolism (OR=5 [95%CI 0.4-58]). Random Forest machine learning models showed modest to no predictive performance of the different omics (area under ROC curve ranged between 0.41-0.67 in CD, and 0.38-0.72 in UC; Table 1).

Conclusion

Key biological pathways were identified in association with severity of disease course in pediatric IBD, utilizing large datasets of genetics, metabolomics and microbiome. The findings offer insights into mechanisms underlying pediatric IBD and highlight potential therapeutic targets as well as biomarkers for early intervention.
P0629 A scoping review of evidence-based dietary guidance and guidelines published by national and international organisations on Inflammatory Bowel Disease
Authors: Dimakis I K , Kapsoritakis A , Argyriou K , Manolakis A , Grammatikopoulou M , Gkikas K , Gerasimidis K , Androutsos O , Svolos V
Published: January 2025

Background

Despite emerging evidence indicating the critical importance of diet interventions for induction and maintenance of remission of inflammatory bowel disease (IBD), we still lack consistent guidelines for diet recommendations and nutrition therapy. The aim of this in-depth scoping review was to identify evidence-based dietary guidance and clinical guidelines produced by national and international organisations on IBD and summarize their content for diet interventions to induce and maintain remission.

Methods

An extensive literature search was undertaken on PubMed (January ‘14 to November ‘24), including MeSH terms (“Inflammatory Bowel Disease” OR IBD OR Crohn’s OR Colitis) AND (diet OR diet* OR food OR nutrition OR nutr*) AND (guideline OR consensus OR “expert review” OR “topical review”). Eligible articles included evidence-based dietary guidance and clinical guidelines for adults living with IBD, produced by national and international organisations. Paediatric guidelines and articles not in English were excluded.

Results

417 records were identified. After full-text review 10 papers fulfilled eligibility criteria. The eligible evidence-based dietary guidance and clinical guidelines were manuscripts produced by the European Crohn’s Colitis Organisation, International Organization For the Study of Inflammatory Bowel Disease, American Gastroenterological Association, European Society for Clinical Nutrition and Metabolism. Australasian society for parenteral and enteral nutrition, British Society of Gastroenterology, British Dietetic Association and the Dietitian Crohn’s Colitis Australian Network. Thirty different interventions were identified within different guidelines, proposed to induce and/or maintain remission for Crohn’s disease (CD) and/or ulcerative colitis. Exclusive enteral nutrition was recommended for induction of remission in CD by 9 out of 10 guideline articles. Similarly, CDED coupled with Partial Enteral Nutrition (PEN) was recommended for induction of remission in CD by 3 out of 10 guideline articles. Partial enteral nutrition was recommended for maintenance of remission in CD by 3 out of 10 guideline articles. Lastly, probiotic supplementation was recommended for induction of remission in UC by 2 out of 10 guideline articles. The remaining interventions were either recommended within a single guideline or there were inconsistent recommendations for their use between organisations.

Conclusion

The findings of this scoping review provide an overview of dietary guidelines by national and international professional organizations and can support collaboration between organizations worldwide thus reducing duplication of effort, facilitating reproducibility, and identifying guidance discrepancies.
P0631 Short-term effectiveness of risankizumab in patients with Crohn´s Disease: Experience in our centre
Authors: Valdés Delgado T , Rodríguez Gallardo M , Maldonado Pérez B , Belvis Jiménez M , Castro Laria L , Argüelles Arias F
Published: January 2025

Background

The recent introduction of Risankizumab to the therapeutic arsenal for Crohn’s disease (CD) has represented a revolution, owing to the positive efficacy outcomes observed in pivotal studies. Our aim was to assess the short-term effectiveness and safety of Risankizumab in CD patients in routine clinical practice.

Methods

A retrospective, observational, single-centre study was conducted, including CD patients undergoing treatment with Risankizumab who had completed at least the induction phase (week 12). The primary endpoint was clinical remission, defined as a Harvey-Bradshaw Index (HBI) ≤ 4. We analysed baseline and end-of-follow-up (weeks 12-24) results for clinical remission, faecal calprotectin (FC), and C-reactive protein (CRP). Additionally, drug persistence at the end of follow-up was also analysed and adverse events were recorded.

Results

A total of 36 patients were included, with a median age of 45 years [IQR 34-54] and a median disease duration of 9 years [3-18]. The predominant location and pattern were ileocolonic and inflammatory, respectively. The 77.8% (28/36) had failed two or more biologics, and 3 patients were biologic-naïve (Table 1).

The median baseline HBI was 8 [IQR 6-8], decreasing to 4 [IQR 2-5] at the end of follow-up between weeks 12-24 (p <0.001) (Figure 1A).

The median baseline FC was 880 μg/g [IQR 640-2200], decreasing to 400 μg/g [220-575] at the last evaluation, between weeks 12-24 (p <0.001) (Figure 1B).

Regarding CRP, the median baseline was 5 mg/L [IQR 2-7], decreasing to 2 mg/L [IQR 2-5] at the end of follow-up (p= 0.003) (Figure 1C).

Up to 94.4% of patients maintained Risankizumab at the end of follow-up (Figure 1D). Adverse events (AEs) were observed in 4 patients, of whom 2 had to discontinue treatment without being able to attribute the experienced AEs to the drug.

Conclusion

In our cohort of CD patients treated with Risankizumab, 64% achieved clinical remission in the short term, maintaining treatment at the end of follow-up in 94%. Our results are comparable to those obtained in the drug’s clinical trials.
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

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<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<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

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 <2.0), histo-endoscopic mucosal improvement (HEMI, Geboes histologic score ≤ 3.1 and endoscopic improvement) and histo-endoscopic mucosal remission (HEMR, Geboes histologic score <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

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% < 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

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

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

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 < 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

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

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< 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<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<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

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 > 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<0.001), discharge score (5 vs 2, p<0.001), daily activity limitation score (4 vs 1, p<0.001) and pads usage per day (4 vs 1, p<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.
P0972 Higher vedolizumab clearance associates with poor therapeutic outcomes during maintenance therapy of vedolizumab in Crohn’s disease
Authors: Anjie MD S , D’Haens G R A M , Baert F , Bossuyt P , Hoentjen F , Clasquin E , Molnar T , Lowenberg M , Vermeire S , Panetta J C , Dervieux T
Published: January 2025

Background

Drug Clearance (CL) is a better pharmacokinetic (PK) metric compared to trough levels (TL) in associating with therapeutic outcome of infliximab, adalimumab and ustekinumab therapy in Crohn’s disease (CD). However, data regarding vedolizumab (VDZ) are limited. We compared the performances of VDZ CL and TL in associating with therapeutic outcomes in CD.

Methods

This retrospective analysis included a subset patients from the LOVE-CD trial at Amsterdam UMC. Blood samples were collected at trough during intravenous VDZ maintenance treatment and stored at -80ºC until analysis. VDZ TL were measured using homogenous mobility shift assay and CL was estimated using nonlinear mixed effect models. Therapeutic outcomes consisted of endoscopic remission (Simple Endoscopic Scoring for CD [SES-CD] <3) measured at one-year after starting treatment, and clinical and biochemical remission status (CRP <3 mg/L with CD activity index <150) at each maintenance cycle. Statistical analyses included receiver operating characteristics (ROC) curves, area under the curve (AUC) and logistic regression.

Results

A total of 50 patients (24 females, mean age 37 years) were evaluated in this analysis. At one year 39 patients had endoscopic data; 17/39 (44%) were in endoscopic remission. In the 50 patients, 38% of cycles (120/312, median 6 per patients) showed clinical and biochemical remission. Median TL and CL were 16.0 µg/mL (IQR: 9.5-23.8 µg/mL) and 0.154 L/day (IQR: 0.125-0.190 L/day) respectively. Anti-drug antibodies to VDZ were negligible in this cohort (2.5%, 8/323 specimens). ROC analysis yielded higher AUC with CL (AUC= 0.824 [95%CI: 0.683-0.964]) than with TL (AUC=0.606 [95%CI: 0.421- 0.790]) (difference= 0.218 95%CI: 0.074- 0.362; p=0.003) in distinguishing endoscopic remission from endoscopic active disease. Similar results were observed with the clinical and biochemical remission outcome (AUC [conc]=0.530 [95%CI: 0.466-0.595] compared to AUC[CL]=0.646 [95%CI: 0.584- 0.709]) (difference: 0.116 95%CI: 0.063- 0.169; p<0.001). Logistic regression revealed that TL were not significantly associated with either of the two outcomes (p>0.28) (Figure). In contrast, higher CL (>0.156 L/day) was associated with 9.0-fold (95%CI: 1.7,44.0) and 2.1-fold (95%CI: 1.3,3.4) lower likelihood of endoscopic and clinical & biochemical remission, respectively (p<0.01) (Table).

Conclusion

These data support the hypothesis that VDZ CL is better than TL in associating with outcomes of VDZ treatment in CD. Given that there was little immune response to VDZ in this study, the association between higher CL and poor outcome most likely reflects higher inflammatory burden that consumes the drug from the central compartment.