DAY 3 - AGA Hosts the Late-Breaking Clinical Science Plenary

Tomotaka Saito, of Tokyo University in Japan, presented the results of the WONDER-02 Trial, a multicenter, randomized controlled non-inferiority trial comparing plastic stents and lumen-apposing metal stents (LAMS) for endoscopic ultrasound-guided drainage of pancreatic pseudocysts. Though LAMS are more popular, plastic stents are more cost effective, and prospective comparative data are limited. Based on available retrospective data, his team hypothesized that plastic stents would be non-inferior to LAMS. The study was conducted in 26 centers and included 39 patients who received a plastic stent and 41 patients who received a LAMS (see Saito et al. Trials. 2024 for the full study design). Patients received a CT with or without MRI prior to drainage, and outcomes included technical success (stent placement) and clinical success, defined as a decrease in cyst size and improvement of inflammatory markers within 6 months. If the endpoints were not achieved with one stent type, patients were offered the other stent type and clinical success was re-evaluated after 6 months. The non-inferiority margin was set at 15%. Baseline demographics were comparable between groups. Only the index procedure time was significantly lower in the LAMS group, and clinical success was the same (97% in the plastic group vs. 95% in the LAMS group). There was also no difference in technical success or safety signals between the two groups. Limitations included the small sample size and lack of blinding. The authors concluded that, given the comparable safety and efficacy, plastic stents could be a cost-effective first-line option for drainage of pancreatic pseudocysts.

Anthony Hopson, PhD, from Alimentary Innervations Ltd, in London, UK, shared findings from the TrIuMPH trial, a randomized, double blind, placebo-controlled Phase 2 trial assessing the safety and efficacy of EBX-102-02, an oral full-spectrum intestinal microbiota product, in patients with irritable bowel syndrome with constipation (IBS-C). The current evidence on the benefits of fecal microbiota transplant comes from 6 trials, but the lack of standardization makes it difficult to draw conclusions. This has led to the development of “microbiome therapies.”  EBX-102-02 is derived from screened human stool donations and contains a diverse consortium of viable microorganisms, an absence of pathogenic organisms, and restricted expression of antimicrobial resistance genes. The product is produced under GMP-controlled, aseptic conditions. The capsule is pH sensitive and dissolves in the duodenum. The TrIuMPH trial tested the hypothesis that EBX-102-02 can restore the microbiome by increasing diversity, promoting engraftment of beneficial species, and reducing methane-producing bacteria, which will alleviate IBS-C symptoms. Dr. Hopson reported results for patients with IBS-C who were randomized 2:1 to EBX-102-02 (n=41) and placebo (n=21), dosed once a week for 7 weeks. Forty of the 41 patients completed treatment with a good safety signal. During the 7 weeks of treatment, symptom severity based on the IBS-SSS score dropped rapidly, with significant separation from placebo by the end of treatment. Sustained improvement was seen in abdominal pain, pain duration, stool form and straining scores, and days with no bowel movement. They also found that 75 new species were engrafted as early as week 1 of treatment. The drug is to be evaluated this summer in a dose-ranging phase 2b study in IBS-C.

Gregory A. Cote, MD, from Oregon Health & Science University in Portland in Oregon, described the findings of the SHARP trial, testing the effect of minor papilla sphincterotomy on the risk of acute pancreatitis in patients with acute recurrent pancreatitis and pancreas divisum. Hundreds of studies, dating back to 1978, have suggested the benefit of papilla sphincterotomy in pancreas divisum, including cohort improvements in patients after ERCP, and decades of experience. Yet retrospective studies used variable definitions of success that are hard to compare and there is little evidence from prospective blinded studies. The goal of the SHARP trial was to examine the effect of the ERCP and minor papillotomy on the incidence of acute pancreatitis more than 30 days after randomization. They also looked at incidence density and time to incidence. All patients underwent EUS and then were randomized 1:1 to ERCP and minor papillotomy or a sham ERCP procedure. A total of 148 patients were enrolled, with 73 randomized to the sham group and 75 to ERCP and minor papillotomy. Both had similar baseline characteristics. The follow-up time was 33 months. The incidence of pancreatitis within 30 days was 35% in the sham group and 44% in the ERCP/minor papillotomy group, with an adjusted hazard ratio of 0.83 indicating no benefit of the surgery. The time to acute pancreatitis was almost the same in both groups, as was incident density, and the incidence of chronic pancreatitis, diabetes mellitus, and pancreatic insufficiency. No significant difference between the groups was seen beyond 30 days, even in a patient who had reported acute pain.

Walter Reinisch, MD, from the Medical University of Vienna in Vienna, Austria, discussed findings from an endoscopic subanalysis of data from the RELIEVE-UCCD phase 2b study of duvakitug (Reinisch et al. J Crohns Colitis. 2025).  TL1A is a proinflammatory cytokine implicated in the pathogenesis of UC, and duvakitug is a human monoclonal antibody that preferentially blocks TL1A binding to its DR3 receptor. The primary endpoint was clinical remission, defined as a Mayo score of ≤2. The topline findings were presented at ECCO. A total of 137 patients were randomized 1:1:1 to placebo (n=44) or low-dose (n=47) or high-dose (n=48) duvakitug. Baseline characteristics were similar across the three groups, including the distribution of immunomodulator and corticosteroid use. At 14 weeks, clinical remission was approximately 27% higher in the duvakitug high-dose group compared to placebo in patients stratified by baseline disease severity (by Mayo endoscopic subscore, MES 2 vs. MES 3). Significant endoscopic improvement and remission rates were also seen. When evaluating the change in MES from baseline to week 14, more patients in the duvakitug groups had shifted to lower MES categories compared to those in the placebo group. Histological endoscopic mucosal improvement was also seen with duvakitug compared to placebo, overall and in the MES 2 and MES 3 subgroups. The safety profile was similar across treatment groups with slightly more adverse events in the MES 3 subgroup.

Florian Tran, from the Universitatskinikum Schleswig-Holstein in Kiel, Schlesswig-Holstein, Germany described findings of the GUIDE-IBD study, a multi-center, randomized, open-label prospective clinical trial evaluating whether biomarker-informed therapy guidance improved clinical outcomes of anti-TNF treatment in patients with inflammatory bowel disease. Many disease-related biomarker candidates have been identified in IBS, but most are not suitable for individualized decision-making due to low individual prediction power or failure to be replicated in independent studies. Early changes in markers within 2 weeks after anti-TNF therapy have been shown to be predictive of longer-term treatment response. Dr. Tran’s group asked whether the entirety of known biomarkers has informative value and can be used by clinicians to select treatment. For this study, they focused on mRNA markers measured in peripheral blood and biopsies, narrowing down the candidate list using random forest feature selection and PCA. This process resulted in a set of 29 blood mRNA markers and 16 biopsy mRNA markers. The GUIDE-IBD trial was a multicenter open-label study in which patients with CD or UC were given infliximab and then randomized to molecular medicine care (n=38) vs. best care (n=54). The patients were followed for 52 weeks with periodic biomarker and endoscopic assessment. A Molecular Medicine Board reviewed biomarker levels to recommend therapy changes in the molecular medicine arm, which could include adjustments in dosing, schedule, addition of medications, and switching. Baseline characteristics were similar in both groups. At 52 weeks, 55% of those in the molecular medicine group vs. 27% in the best care group achieved improvement in endoscopic endpoints and 61% in the molecular medicine group vs. 33% in the best care group achieved deep remission. Therapy switches were more frequent in the molecular medicine group (47%) vs. the placebo group (29%), with more frequent switches later in the follow-up period. Dr. Tran emphasized that this was a proof-of-concept study of the effect of integrating molecular medicine into therapeutic decision-making. Implementation would require a quality-controlled integrated healthcare environment with sufficient infrastructure for follow-up. One of the attendees referred to this as a “supercharged treat-to-target” approach.