ECCO News Editors’ Summary of the top 15 DOPs at ECCO'25

   Summary of top 15 DOPs                                  

The winners of the Top 15 DOP awards are

DOP006: Long term maintenance treatment with vedolizumab in paediatric IBD: a three-year follow-up of the prospective multicentre VEDOKIDS study

Dan Turner, Jerusalem, Israel

In this multicentre prospective cohort study, Atia et al. evaluated the efficacy and safety of vedolizumab in paediatric patients with Crohn's Disease (CD) and Ulcerative Colitis (UC) over three years. Children commencing vedolizumab were recruited from 17 centres across Europe, the United States and the Middle East, regardless of disease severity.

The primary outcome was complete clinical remission, defined as steroid-free and biochemical remission with ongoing treatment, while the secondary outcome was loss of response, as indicated by a PUCAI of ≥10 in UC and a wPCDAI of ≥12.5 in CD, among those achieving clinical remission at week 6.

Out of 137 recruited patients, 53 (39%) remained on vedolizumab. Treatment persistence was significantly higher in UC (48%) than in CD (28%). Complete remission at three years was achieved by 26% of UC patients and 14% of CD patients, with clinical remission at week 6 being the best predictor of success. However, many patients who were in remission at week 6 lost their response by year 3.

There were 40 adverse events in 23 patients (17%), none serious, with headaches, myalgia and fever being the most common.

The study showed that vedolizumab was effective and safe for paediatric patients; however, a significant number of patients eventually lost response to the treatment.

DOP017: Infliximab induction fails to reach targets in Perianal Fistulizing Crohn’s Disease: first results from the ATLANTIC study

Lieven Mulders, Amsterdam, the Netherlands

Mulders et al. found that the standard dose of intravenous infliximab (5 mg/kg) resulted in significantly lower trough levels (IFX TL) in patients with perianal fistulising Crohn’s Disease (PFCD) compared to those with luminal Crohn's Disease (CD). The study included 149 patients (69 with PFCD and 86 with CD). Target trough levels were 20 μg/mL at week 2, 15 μg/mL at week 6, and 10 μg/mL for PFCD and 5.0 μg/mL for CD patients at week 14.

During induction, 57% of CD patients reached the target IFX TL, versus 43% of PFCD patients (p=0.03). Median IFX TL at week 14 was lower in PFCD patients (2.8 μg/mL) than in CD patients (4.8 μg/mL, p=0.014). Only 9% (5/57) of PFCD patients achieved the target level at week 14, compared to 46% (36/78) of CD patients (p<0.0001). Anti-drug antibodies were found in 16% of PFCD and 12% of CD patients (p=0.169).

These results suggest that standard infliximab dosing may be insufficient for PFCD patients, indicating a need for alternative dosing strategies.

DOP027: Caudovirales may trigger molecular mimicry mechanisms in Crohn’s Disease

Carmela Errico, Milan, Italy

Errico et al. examined the role of Caudovirales in Crohn's disease (CD) pathogenesis using an IBD transcriptome and meta-transcriptome meta-analysis framework, analysing immune and non-immune cell populations from intestinal biopsies of healthy controls and CD patients. Their findings confirmed increased levels of Caudovirales, particularly Proteus virus Isfahan, in the cells of CD patients, especially in dendritic cells and macrophages. Viral proteins gp16 and gp82 exhibited structural homology with human thymidylate synthase and dCMP deaminase, supporting the hypothesis of molecular mimicry. This mimicry could lead to misrecognition, triggering autoimmunity and sustaining the inflammatory environment in CD patients.

DOP030: Mucosal deficiency of mitochondria-driven humoral immunity is linked to Crohn’s Disease

Annika Raschdorf, Lübeck, Germany

Raschdorf et al. examined the characterisation of colonic immunoglobulin-secreting plasma cell (PC) differentiation in patients with Crohn's Disease (CD). They performed in-depth phenotyping of patients in remission and non-IBD controls using multi-omics analyses of plasma and colonic biopsies. The study investigated the impact of mitochondrial function on colonic PC maturation.

Patients with CD exhibited reduced levels of mucosal dimeric IgA and faecal IgA compared to non-IBD controls. Spatial single-cell proteomics revealed an increase in colonic plasmablasts and immature CD19+CD45+ PCs, at the expense of the fully mature CD19-CD45- phenotype. Metabolic phenotyping indicated mitochondrial dysfunction in colonic PCs, characterised by increased expression of cell-surface NADase CD38 and decreased expression of mitochondrially encoded transcripts.

The study established a link between mitochondrial dysfunction in plasma cells and impaired differentiation, leading to reduced secretory IgA levels and compromised mucosal barrier integrity.

DOP044: Active disease on intestinal ultrasound in pregnancy is associated with an increased risk of adverse obstetric and neonatal outcomes: an international multi-centre prospective cohort study

R Prentice, Fitzroy, Australia

Prentice et al. evaluated whether active disease, defined by intestinal ultrasound (IUS), can predict adverse pregnancy outcomes in Inflammatory Bowel Disease (IBD) patients. This multi-centre prospective cohort study involved 379 participants, including 200 with Crohn's Disease (CD), from Australia and the United States. Clinical assessments and faecal calprotectin (FCP) testing were conducted preconception, during each trimester and at six weeks postpartum, with IUS performed preconception and at T1 and T2.

Active disease was identified by a Patient Global Assessment (PGA) >1, Harvey-Bradshaw Index (HBI) >5 or Simplified Clinical Colitis Activity Index (SCCAI) >3. IUS remission was defined as bowel wall thickness (BWT) <3 mm across all segments.

Findings indicated that maximum BWT >6 mm in T1 was linked to a threefold increase in neonatal intensive care admissions, while in T2 it was associated with a fourfold increased risk of prematurity. IUS hyperaemia in T2 correlated with elevated pre-eclampsia risk. The study noted weak agreement between clinical assessments and objective IUS/FCP activity, suggesting that IUS monitoring may be a valuable tool in routine antenatal care for IBD patients.

DOP053: Efficacy of appendectomy in inducing remission in moderate-to-severe ulcerative colitis: preliminary one year results of a multicentre prospective cohort study (COSTA)

Eva Visser, Amsterdam, the Netherlands

Visser et al. evaluated the efficacy of appendicectomy in patients with moderate to severe active Ulcerative Colitis (UC) unresponsive to biologics or small molecules. This multicentre, prospective study included 120 patients aged ≥16 years with active UC (total Mayo score ≥5). Participants underwent either laparoscopic appendicectomy or continued step-up therapy with a JAK inhibitor or proctocolectomy.

The primary outcome was the proportion of patients achieving clinical remission (total Mayo score ≤2) at 12 months without treatment failure. Overall, 65 patients had appendicectomy, 50 switched to JAK inhibitors and five had proctocolectomy. Concomitant steroid use was higher in those switching to JAK inhibitors (46.0%) or undergoing proctocolectomy (80.0%) compared to the appendectomy group (26.2%, p=0.01).

The appendectomy group showed a significantly greater rate of clinical remission at 12 months without treatment failure compared to the JAK inhibitor group (33.8% vs 12.0%, p=0.007).

DOP056: TDM-Based Dose-Intensification of Infliximab is not Superior to Standard Dosing in Patients with Acute Severe Ulcerative Colitis: Results from the TITRATE Study

Joep Van Oostrom, Amsterdam, the Netherlands

In this prospective open-label, multicentre randomised controlled trial, Gekse et al. assessed whether personalised therapeutic drug monitoring (TDM)-driven induction dosing of infliximab (IFX) was superior to standard dosing. A total of 48 patients were recruited, with 23 receiving personalised dosing (PD) and 25 standard dosing (SD). By week 26, 31 patients completed the treatment (19 PD, 12 SD).

Patients in the SD group received 5 mg/kg IFX at weeks 2 and 6, while the PD group received additional infusions guided by a Bayesian pharmacokinetic algorithm, targeting serum concentrations >28 μg/mL for the first 28 days and >15 μg/mL thereafter. All patients received maintenance 5 mg/kg IFX every 8 weeks after day 42.

The primary endpoint was clinical and endoscopic response by day 42 (Lichtiger score <10 with a ≥3 point decrease and UCEIS ≥2 point decrease). The median cumulative IFX dose at day 42 was 18.41 mg/kg for PD versus 13.79 mg/kg for SD. The primary endpoint was not met in the PD group [13/23 (56.5%) vs 11/25 (44.0%), p=0.564], indicating that personalised dosing was not superior to standard dosing in acute severe UC.

DOP068: Vedolizumab counteracts Parkinson’s disease-related brain pathology driven by gut-primed IBD T cells

Elizaveta Gerasimova, Erlangen, Germany

Gerasimova et al. investigated how gut-primed T cells from Inflammatory Bowel Disease (IBD) patients may contribute to neurodegenerative processes in Parkinson's disease (PD). Using the Kaede T Cell Transfer model, they demonstrated that gut-primed T cells can cross the blood–brain barrier during chronic intestinal inflammation. Neurons expressed MAdCAM-1, which was also identified in single-cell RNA sequencing of postmortem brain tissue.

The study found that α4β7+ IBD T cells accumulated near neurons, leading to neuronal cell death and alpha-synuclein (aSyn) aggregation, a hallmark of PD. Treatment with vedolizumab reduced IBD T cell accumulation in human stem cell-derived brain organoids and preserved neural cell integrity. Blocking α4β7-mediated T cell neurotoxicity and aSyn pathology may offer a promising therapeutic strategy for IBD patients at risk of neurodegenerative diseases such as PD.

DOP076: Translational and preclinical study validating anterior gradient 2 as a novel epithelial therapeutic target in Inflammatory Bowel Disease (IBD) involved in inflammation, fibrosis, and intestinal barrier integrity

Xavier Tretón, Neuilly, France

Anterior Gradient 2 (AGR2) is an endoplasmic reticulum resident protein that, under stress, is secreted into the extracellular milieu, disrupting epithelial integrity, attracting monocytes and activating fibroblasts. Tretón et al. investigated the link between AGR2 tissue expression in Inflammatory Bowel Disease and the efficacy of a neutralising antibody (TH-009) in murine models.

The study included 132 endoscopic biopsies from 66 patients with Crohn's Disease, 50 with Ulcerative Colitis and 16 controls, along with 96 surgical samples. All patients with mucosal inflammation exhibited AGR2 overexpression, and 38% of histologically healed patients with high AGR2 levels had a relapse rate at 18 months three times higher than controls.

In a murine acute colitis model (3% DSS), intravenous TH-009 treatment improved weight, global colitis DAI score and histological colitis score compared to controls. It significantly reduced macrophage and T lymphocyte infiltration, myeloperoxidase activity and pro-inflammatory cytokines TNFα and IL-6, while restoring intestinal permeability. In a fibrosis model, TH-009 reduced digestive fibrosis by 49% and submucosal fibrosis thickness by 59%.

DOP084: Development of a core outcome set for Inflammatory Bowel Disease patients with stomas

Lakshman Kumar, Dublin, Ireland

Kumar et al. developed a core outcome set (COS) for Inflammatory Bowel Disease (IBD) patients with stomas. They identified 88 candidate outcomes through a systematic review (68 outcomes) and online patient focus groups (11 outcomes), with nine additional outcomes from the study working group.

Seventy-six stakeholders (73.1% response rate) from 17 countries participated in a two-round Delphi process, refining the list to 37 outcomes. In a consensus meeting, 37 experts and patients established a six-domain COS, including maintenance of hydration, nutritional status, symptom-based clinical activity, objective disease activity markers and two quality of life (QOL) domains (IBD-related and stoma-specific QOL).

This COS will support the development of measurement instruments for IBD patients with stomas, ensuring that this underrepresented cohort is included in future clinical trials.

DOP097: Emulsifier restriction is an effective therapy for active Crohn’s disease: the ADDapt trial - a multi-centre, randomised, double-blind, placebo-controlled, re-supplementation trial in 154 patients

Aaron Bancil, London, United Kingdom

Bancil et al. conducted a study to assess the effects of a low emulsifier diet (LED) compared to a control diet on disease activity in patients with mild to moderately active Crohn’s disease (CD) over 8 weeks. Patients with a Crohn’s Disease Activity Index (CDAI) score of 150-250 and objective signs of inflammation (either faecal calprotectin levels ≥150 µg/g or confirmed by endoscopy/radiology) were randomized into two groups: those on LED and those receiving LED with emulsifier re-supplementation (control). Of the 154 patients recruited, 113 (73%) completed the trial. At week 8, CDAI response (≥70 reduction) was achieved by 39 patients (49.4%) on LED compared to 23 patients (30.7%) in the control group (p=0.019). Importantly, there were no serious adverse events reported during the study.

DOP106: Geographic disparities in Healthcare Utilisation in people with inflammatory bowel disease, Crohn’s Colitis Cure Data Insights Program

Jane Mary Andrews, Sydney, Australia

Andrews et al. examined healthcare utilization (HCU) through an IBD electronic management record, revealing differences in care between ulcerative colitis (UC) and Crohn’s disease (CD) patients. UC patients underwent endoscopy at higher rates, while CD patients had more radiology assessments; however, the overall rates for both procedures were lower than expected. Additionally, helpline contacts were less frequent among UC patients compared to their CD counterparts. Residing in non-metropolitan areas correlated with lower usage rates of radiology (p<0.05) and clinical assessments (p<0.01), but higher helpline contact rates. These findings highlight disparities in healthcare utilization, suggesting potential inequities in health outcomes and access to care.

DOP109: A necroptotic-to-apoptotic signaling axis underlies inflammatory bowel disease

Britt Christensen, Parkville, Australia

Christensen et al. investigated cell death pathways in patients undergoing advanced therapies for inflammatory bowel disease (IBD). The study involved analysing over 900 paired intestinal biopsies from 52 IBD patients and 28 non-IBD controls, focusing on inflamed, marginal, and non-inflamed tissue. The results revealed increased necroptotic and apoptotic signalling in IBD patients, correlating with levels of intestinal inflammation, regardless of treatment. Notably, necroptotic signalling was observed in non-inflamed IBD tissue, indicating early activation in the disease progression, while apoptotic signalling was predominantly present in inflamed areas. Bulk RNA sequencing further demonstrated that inflammation-induced transcriptional reprogramming of epithelial cells resulted in a macrophage-like phenotype, which promoted RIPK1-independent necroptotic signalling.

DOP126: Circulating neutrophils exhibit distinct transcriptional and maturity changes in CD and UC that relate to pathogenic Th1/17 CD4+ memory T cell responses

M. Fernanda Pascutti, Rotterdam, The Netherlands

Neutrophils play a critical role in intestinal damage in Crohn’s disease (CD) and ulcerative colitis (UC), yet their immunological roles in disease heterogeneity are often overlooked. The study by Pascutti et al investigates the differences in neutrophil function between and within CD and UC, influenced by pathogenic Th1/17 CD4+ memory T cell (Tm) responses. The analysis involved 33 therapy-naive pediatric CD patients, 12 UC patients, and 11 IBD-negative controls from the PIBD-SETQ cohort, examining RNA sequencing, flow cytometry, and plasma proteomics.

Results revealed 263 differentially expressed genes (DEG) in CD vs IBD-negative controls and 421 DEG in UC vs IBD-negative controls, with 137 common genes. Notably, CD neutrophils exhibited activation of IFN-related pathways absent in UC neutrophils, which displayed phenotypic immaturity characterized by lower CD10, CD16, and CXCR2 surface expression. High interpatient heterogeneity was noted in neutrophil profiles within CD and UC. Clustering revealed distinct patient subgroups, with UC1 patients having elevated granule protein expression correlated with higher plasma IL-17A, while CD2 patients showed increased IFN-signalling related to higher plasma concentrations of IFNg. These findings suggest that neutrophil transcriptional changes impact their function, contributing to disease pathogenesis in individual patients.

DOP135: Patient-specific regulatory network rewiring in Inflammatory Bowel Disease: How genetic polymorphisms divert incoming signals and contribute to disease pathogenesis

John P Thomas, London, United Kingdom

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), results from complex interactions between environmental factors and genetic risk loci, particularly single nucleotide polymorphisms (SNPs). Many IBD-related SNPs reside in non-coding regions that influence transcription factor (TF) binding, potentially altering regulatory mechanisms. Understanding these upstream signalling pathways is crucial for revealing how non-coding genetic variants affect downstream cellular processes.

To investigate this, a novel systems genomics pipeline was developed by Thomas et al.  to analyse genotype data from 2,636 IBD patients, predicting changes in TF binding due to SNPs compared to healthy individuals. By annotating these TFs using the Gene Ontology database, shifts in upstream signalling pathways were inferred. The analysis found that UC patients gained 144 incoming signals while CD patients gained 138, with 95 signals shared between the two conditions, indicating common regulatory mechanisms. Both diseases exhibited a net loss of incoming signals, suggesting significant rewiring of upstream pathways. These signals were associated with immune response, epithelial barrier function, and stress responses. This study emphasizes that IBD-associated SNPs influence disease pathogenesis not only through downstream effects but also by altering upstream signalling processes, providing insights into IBD mechanisms.