Introduction

Differences in endoscopic response and biological features across ileal, ileocolonic, and colonic Crohn’s disease (CD) suggest distinct mechanisms for healing. We developed an endoscopic clustering method using segmental intestinal endoscopic scores in patients with moderately to severely active CD to investigate the potential influence of regional mucosal heterogeneity on treatment effect. We then evaluated endoscopic outcomes across subtypes between placebo (PBO), guselkumab (GUS), and ustekinumab (UST) in the Phase 3 GALAXI 2 and 3 studies.

Aims & Methods

Endoscopic clustering was established using baseline segment Simple Endoscopic Score for CD (SES-CD) values from terminal ileum, right colon, transverse colon, left/sigmoid colon, and rectum from cohort 1 (1233 patients, GALAXI 1, GALAXI 2, GRAVITI trials) and cohort 2 (525 patients, GALAXI 3). Patient clusters were identified using consensus hierarchical clustering, and a machine learning classification model was developed for patient cluster assignment of cohort 2. GALAXI 2 and GALAXI 3 patients were combined to evaluate Week (WK) 12 and WK48 endoscopic outcomes between PBO, GUS, and UST.

Results

We identified 7 CD endoscopic subtypes (ileum only, ileum dominant, right colon dominant, mid-colon, colonic, ileocolonic, rectum dominant), highlighting heterogeneity within Montreal classification. In total, GUS showed higher endoscopic remission rates than UST at WK12 and at WK48. Patient clusters were used with baseline stricturing data (SES-CD narrowing > 0) to consolidate groups with differential treatment effects: Group 1 (62% of patients, mixed ileocolonic/colonic) showed similar endoscopic remission rates at WK12 between GUS (26%) and UST (27%) with higher rates for GUS at WK48 (39-44% GUS, 30% UST); Group 2 (ileum only) and Group 3 (characterized by strictured right colon), totaling 38% of patients, showed higher endoscopic remission rates with GUS at WK12 (19%, 20%), where UST showed placebo-like efficacy (7%, 2%), with higher rates with GUS at WK48 (Group 2: 20-26% GUS, 18% UST; Group 3: 28-30% GUS, 12% UST). Endoscopic responders to GUS, and not UST, at WK12 in Group 2 and 3 patients with baseline stricturing showed greater reduction in narrowing than non-responders, contributing to 21% vs 5% reduction in total SES-CD.

Conclusion

Endoscopic patient clustering provides higher resolution of CD subtypes to delineate differential treatment effects. GUS demonstrated endoscopic efficacy across all patients at WK12, where UST showed placebo-like efficacy in 38% of patients, supporting superior endoscopic efficacy over UST across all patients by WK48. Reductions in narrowing with GUS proposes a role of GUS in affecting stricture biology in addition to broader segment-specific molecular treatment effects that will be explored in future research.

Disclosure

Dylan Richards, Loqmane Seridi, Klebea Sohn, Brad Mcrae, Natalie A. Terry, Marion Vetter, Daniel Cua, Patrick Branigan are employees of Janssen and may hold stock in Johnson & Johnson.
Walter Reinisch reports serving as a speaker for AbbVie, Celltrion, Ferring, Janssen, Galapagos Medice, MSD, Roche, Pfizer, Sobi, Takeda; serving as a consultant for AbbVie, Amgen, AOP Orphan, Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celltrion, Eli Lilly, Galapagos, Gilead, Index Pharma, Janssen, Medahead, Microbiotica, Pfizer, and Takeda; serving as an advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Galapagos, Janssen, and Pfizer; and receiving research funding from AbbVie, Janssen, Sandoz, Sanofi, and Takeda.
Raja Atreya has served as a speaker or consultant, or received research grants from AbbVie, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, DrFalk Pharma, Galapagos, Gilead, InDex Pharmaceuticals, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Novartis, Pandion Therapeutics, Pfizer, Roche, Samsung Bioepis, Takeda, and Viatris.

Introduction

It remains uncertain if the addition of Saccharomyces boulardii (S. boulardii) to Vonoprazan-amoxicillin dual therapy as a first-line treatment can enhance the Helicobacter pylori (H. pylori) eradication rate and decrease the incidence of adverse events. Therefore, we conducted the randomized controlled trials (RCTs) to address this issue.

Aims & Methods

This is a single-center, prospective randomized controlled study. A total of 150 eligible patients, recruited from December 2023 to November 2024, were randomly assigned to the VA (vonoprazan 20 mg twice daily, amoxicillin 750 mg 3 times daily for 10 days) and VAS groups (vonoprazan 20 mg twice daily, amoxicillin 750 mg 3 times daily, and S. boulardii 250 mg twice daily for 10 days). The eradication rates, adverse events, safety, and compliance were compared between the two groups. Factors associated with eradication rate were explored.

Results

The eradication rates of VA and VAS were 89.3% and 93.3%, respectively, by intention-to-treat analysis (P = 0.384); 93.1%, and 94.6%, respectively, by per-protocol analysis (P=0.966). The incidence of adverse events significantly lower in the VAS group (5.4%) than in the VA group (22.2%; P=0.003). There was no significant difference in compliance between the VA (96%) and VAS groups (98.7%, P = 0.612). Body surface area (BSA) was found to be a influencing factor for eradication rate in both VA and VAS groups. Serum chemistry tests revealed no significant differences in liver and kidney function before and after treatment in both groups.

Conclusion

Although the addition of S. boulardii to VA dual therapy could not increase the eradication rate, it could decrease the incidence of adverse events. Low-BSA patients are more suitable candidates for this regimen.

Introduction

Helicobacter pylori (HP) has been designated as a Grade I Carcinogen by the WHO and remains an important factor in the pathogenesis of intestinal-type gastric cancer. Gastric cancer was the fifth most common malignant disease in the world in 2022 (Globocan) with 968,784 new cases(1), after lung, breast, colorectal and prostate cancers. The incidence of gastric cancer has changed significantly since the first estimates in 1975, when stomach cancer was the leading cancer, and one of the most important factors has been the eradication of HP.(2)

Aims & Methods

The purpose of this study was to determinate the trends in the incidence of HP in our region, and also of the precancerous lesions.
There have been included in the study a group of 12541 patients from the years 2014-2018 and a group of 7138 patients from more recently years 2020-2024.
All the patients had dyspeptic syndrome and in all the patients upper digestive endoscopy has been performed in the Gastroenterology Clinic from Târgu Mureș, Emergency Clinical Hospital. Patients with haemorrhage were excluded from the study. In all the patients gastric biopsies and histopathological exam were made, OLGA classification was used.

Results

From the first group, in 2131 patients (52,9% males and 47,1% females) were found gastric changes. Histopathological, 32,7% of the patients had atrophic gastritis, 43,1% intestinal metaplasia (23,7% complete metaplasia and 19,4% incomplete metaplasia) and 0,7% dysplasia. Active gastritis/pangastritis with HP was identified in 59,3% of the patients. In 4,8% of cases there were revealed polyps (hyperplastic, adenomatous) and were removed.
In the second group from 2560 patients (54,4% males and 45,6 females) that underwent upper gastrointestinal with biopsy sampling, HP was present in 442 patients (17,26%.) Histopathological, 14,50% of the patients had atrophic gastritis, 23,8% intestinal metaplasia and 2,58% dysplasia.

Conclusion

HP incidence is decreasing, as it has been treated by the gastroenterologist and also by the general practitioner. The decreasing in incidence of HP is corelating with the decreasing of the precancerous lesions and gastric cancer, so ​it is worth to treat it.

References

1. Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer incidence and mortality worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: Inter- national Agency for Research on Cancer Available from: http://globocan.iarc.fr. Accessed 27.03.2025
2. Malfertheiner P, Megraud F, Rokkas T, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report, Gut 2022;71:1724–1762.

Disclosure

no conflict of interest

Introduction

Helicobacter pylori (Hp) infection is highly prevalent in Portugal, affecting over 60% of the population. Antibiotic resistance poses a significant challenge to Hp treatment; however, empirical regimens remain the standard of care over susceptibility-guided approaches. This study aims to evaluate the most recommended therapeutic options for Hp eradication and to identify risk factors associated with treatment failure.

Aims & Methods

Prospective cohort study conducted in a single centre, including all patients treated for Hp infection between 2013 and 2024. We analysed four eradication regimens: triple therapy (Tri), bismuth quadruple therapy (QuadB), concomitant quadruple therapy (QuadC) and sequential quadruple therapy (QuadS). We collected data on patient demographics and clinical characteristics and compared adherence rates, treatment effectiveness and incidence of adverse events.

Results

Included 591 patients, with a median age of 57 years (IQR 47-66) and female sex 57.2%. The main indication for Hp testing was dyspeptic symptoms (61.1%). The prescribed therapeutic regimens were QuadC in 34.0% of patients, QuadB in 32.8%, Tri in 23.2% and QuadS in 10.0%. According to the intention-to-treat analysis, QuadC (92.9%) and QuadB (90.4%) showed significantly higher eradication rates compared with Tri (73.9%, p<0.001), with no difference observed for QuadS (84.2%, p=0.30 vs QuadC; p=0.61 vs QuadB). Adverse events were significantly less frequent with Tri (0.06%) and QuadS (0.02%) compared to QuadC (0.18%, p<0.01) and QuadB (0.17%, p<0.05), but overall adherence to treatment was 97.1%, with no significant difference among regimens (p=0.19). Logistic regression identified predictive factors for treatment failure: prior eradication attempts (OR 2.31; 95% CI 0.3-1.4), poor adherence (OR 14.5; 95% CI 0.7-4.7) and absence of statin use (OR 2.33; 95% CI 0.07-1.6), with an AUC of 0.72.

Conclusion

QuadC and QuadB therapies are more effective for Hp eradication but are associated with increased rates of adverse events, without a negative impact on overall treatment adherence. Therapeutic failure is more likely in non-naive patients, those with poor adherence to treatment and without statin use.

Introduction

Minocycline is considered the most potent semi-synthetic tetracycline, demonstrates promising pharmacokinetic and antimicrobial properties against Helicobacter pylori (H. pylori). While previous studies suggested the efficacy of minocycline-containing bismuth quadruple therapy for H. pylori eradication, real-world evidence remains limited.

Aims & Methods

his study aimed to evaluate the clinical efficacy, safety, and cost-effectiveness of minocycline-containing bismuth quadruple therapy in routine clinical practice.This multicenter, real-world observational study was conducted at 25 hospitals in Fujian China between January and March 2025. Patients diagnosed with H. pylori infection received one of three 14-day bismuth-containing quadruple regimens with b.i.d. esomeprazole 20 mg and bismuth 220 mg, plus amoxicillin 1000 mg b.i.d. and clarithromycin 250 mg b.i.d. (PBAC), or minocycline 100 mg b.i.d. and clarithromycin 250 mg b.i.d. (PBMC), or minocycline 100 mg twice b.i.d. and levofloxacin 500mg q.d. (PBML). The primary outcome was the H. pylori eradication rate, secondary outcomes included the frequency of adverse events, patient compliance, and cost-effectiveness.

Results

A total of 347 patients were enrolled, with 110 patients completing treatment in each group. In the intention-to-treat (ITT) analysis, eradication rates were 77.4% (PBAC), 85.5% (PBMC), and 84.3% (PBML). In the per-protocol (PP) analysis, eradication rates were 80.9%, 90.9%, and 88.2%, respectively. Although the differences among the three regimens were not statistically significant, minocycline-based regimens achieved numerically higher eradication rates. Adverse event incidence was 32.73%, 20.91%, and 23.64% in the three groups, respectively. Compliance rates exceeded 94% across all groups. Cost-effectiveness analysis showed PBML had the lowest cost-effectiveness ratio (5.38 CNY per 1% eradication), followed by PBAC (5.41 CNY) and PBMC (6.06 CNY).

Conclusion

H. pylori eradication, with favorable patient compliance and pharmacoeconomic profiles. These regimens present a viable alternative to traditional amoxicillin-or tetracycline-based therapies. Further large-scale randomized controlled trials are warranted to confirm these findings.

Introduction

No clinical trial has previously assessed the best therapeutic strategy between switching to another anti-TNF or swapping to another class of biologic class after the failure of a first anti-TNF in ulcerative colitis (UC). The aim of the EFFICACI trial was to compare the efficacy of vedolizumab to infliximab in patients who had failed a first sub-cutaneous anti-TNF (golimumab and/or adalimumab).

Aims & Methods

EFFICACI was a French double-blind multicenter randomized controlled trial (1:1) comparing intravenous vedolizumab 300 mg at weeks 0-2-6 to intravenous infliximab 5 mg/kg at weeks 0-2-6. Eligible patients had moderate-to-severe UC, defined by a total Mayo score ≥ 6 with an endoscopy subscore ≥ 2, despite at least 12 weeks (W) of treatment with adalimumab or golimumab as first line of advanced therapy. The primary endpoint was steroid free clinical remission at W14 (total Mayo score ≤2 without subscore >1 including an endoscopic subscore ≤ 1). Clinical response was defined as a decrease in partial Mayo score ≥3 points and ≥30% from inclusion and a decrease in rectal bleeding score ≥1. The number of patients (N=150) was estimated for a 20% difference in favor of vedolizumab with a type 1 risk of 5% and a power of 80%. Patients were subsequently followed in an open-label fashion until week 54. The analysis was performed on an intention-to-treat basis. Only results at W14 will be presented. (CPP: 2018-002673-21; ClinicalTrial: 35RC17_8841_EFFICACI)

Results

From January 2018 to December 2023, 151 patients were randomized among 19 centers: 78 in the vedolizumab arm and 73 in the infliximab arm. One patient randomized to the infliximab arm did not receive treatment and considered as failure regarding the ITT analysis. Characteristics and demographics at inclusion were similar between groups, with 102/151 (67.5%) patients failing adalimumab and 49/151 (32.5%) failing golimumab. Concomitant immunosuppressive treatment with thiopurine or methotrexate was associated with infliximab and vedolizumab for 37/72 (51.4%) patients and 43/78 (55.1%) patients, respectively. At W14, proportions of patients in clinical remission (primary endpoint) were 34.6% (27/78) with vedolizumab and 19.2% (14/73) with infliximab (p=0.033). The clinical response rates were 46/78 (59.0%) with vedolizumab and 36/72 (50.0%) with infliximab (p=0.27). Proportions of patients in clinical response at W2, W6 and W14 are shown in Figure 1. At W14, endoscopic improvement (Mayo endoscopic subscore 0 or 1) was observed in 36/77 (46.8%) patients in the vedolizumab arm and 21/72 (29.2%) in the infliximab arm (p=0.027). No factor at inclusion was predictive of remission at week 14, including pharmacokinetic data for the first-line anti-TNF. Adverse event rates were similar in both groups - 46 (63.9%) infliximab arm, 55/78 (70.51%) vedolizumab arm. Before week 14, a colectomy was indicated in one patient in the vedolizumab arm; eight patients were hospitalized for a severe flare (5 in the infliximab arm and 3 in the vedolizumab arm). At W54, proportions of patients in clinical remission and still treated with the treatment allocated after randomization were 34 (46.6%) with vedolizumab and 25 (36.2%) with infliximab (p=0.21). Data at W54 are still under investigation at the time of abstract submission.

Conclusion

After failure of a first subcutaneous anti-TNF, induction therapy with vedolizumab was superior to infliximab in achieving steroid free clinical remission at week 14 in patients with UC.

Disclosure

National grant by the French PHRC, grant from takeda