Introduction

Despite the availability of clinical guidelines, a wide range of alternative Helicobacter pylori (H. pylori) eradication regimens continue to be used in routine clinical practice. Data on the frequency and effectiveness of these less frequently prescribed regimens remain limited.

Aims & Methods

Aim: To evaluate the prescription patterns and effectiveness of less frequently prescribed eradication regimens within the European Registry on Helicobacter pylori Management (Hp-EuReg).
Methods: International, multicentre, prospective, non-interventional registry on the management of H. pylori infection, ongoing since 2013. For this analysis, treatment regimens prescribed in fewer than 5% of all cases were classified as 'less frequently prescribed'. Additionally, therapies not previously categorized in the registry database were also included. Treatment effectiveness was assessed using modified intention-to-treat (mITT) and per-protocol (PP) analyses.

Results

Overall, 260 less frequently prescribed regimens were identified, representing 5.5% of all recorded prescriptions (82,510). A total of 2,853 (63%) of these regimens were used as first-line therapy. Among these less frequently prescribed regimens, the most frequently used first-line treatments encompassed bismuth-containing quadruple therapy with PPI–clarithromycin–metronidazole–bismuth (20%), followed by non-bismuth hybrid quadruple therapy with clarithromycin–amoxicillin–metronidazole (9.5%), and dual therapy with PPI–amoxicillin (8.6%). In second-line, the most common regimens were triple therapies, such as the PPI–amoxicillin–moxifloxacin (16%), PPI–clarithromycin–levofloxacin (11%), and PPI–metronidazole–levofloxacin (9.5%). In third-line, the most frequently used regimes were bismuth-based quadruple regimens including PPI–metronidazole–doxycycline–bismuth (27%), followed by triple therapies with PPI–clarithromycin–levofloxacin (6.8%) and PPI–amoxicillin–moxifloxacin (5.6%). In the fourth-line, the most frequent prescriptions were: bismuth-based quadruple therapies including PPI–amoxicillin–rifabutin–bismuth (30%) and PPI–metronidazole–doxycycline–bismuth (11%). Finally, the fifth treatment-line accounted for some less common treatments, such as the dual therapy with PPI–amoxicillin (19%) and the triple therapy with PPI–amoxicillin–bismuth (18%). Effectiveness and frequency of use in first-, second- and third-line of treatment are described in Table 1. Antibiotic-free regimens such as the combination of a PPI with a probiotic —generally Lactobacillus bulgaricus or Lactobacillus reuteri—were prescribed as alternative therapeutic approaches in 104 cases (2.3%), achieving 74% mITT and 76% PP overall effectiveness.
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Conclusion

Among the various less frequently used H. pylori eradication regimens, only a few (such as the PPI-clarithromycin-metronidazole-bismuth regimen and the hybrid regimen including clarithromycin–amoxicillin–metronidazole) achieved first-line eradication rates above 90%. In subsequent treatment lines, effectiveness was highly variable and often suboptimal. These findings highlight the importance of evidence-based treatment selection to optimize treatment outcomes.

Disclosure

Conflict of interest statement
Olga P. Nyssen has served as a speaker or has received research funding from Allergan, Mayoly Spindler, Richen, Biocodex and Juvisé.
Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from Mayoly, Allergan/Abbvie, Diasorin, Richen, Juvisé, Biocodex.
The remaining authors declare no conflicts of interest.

Introduction

Inflammatory bowel disease is a chronic, relapsing condition influenced by genetic, microbial, and environmental factors. This study evaluated the therapeutic potential of multi-strain probiotics in mitigating the severity of experimentally induced colitis in rats, focusing on clinical outcomes, histopathological changes, inflammatory markers, and microbiota changes.

Aims & Methods

Thirty six-week-old male Sprague-Dawley rats were randomly assigned to three groups: Control, Acute Colitis (AC), and Probiotic Treatment (RP; receiving Lactobacillus rhamnosus and Lactobacillus paracasei). Probiotics were administered orally once daily, beginning three days prior to colitis induction with rectal DNBS and continued for seven days post-induction. On day eight, colon tissues and blood samples were collected for histological and biochemical analysis, and fecal samples were analyzed to assess gut microbiota composition.

Results

The AC group showed significantly elevated TNF-α levels compared to the Control and RP groups (p < 0.001), while probiotic treatment significantly reduced TNF-α levels compared to the AC group (p = 0.002, p < 0.001, respectively). Although the RP group demonstrated increased IL-10 levels and decreased MDA levels, these changes were not statistically significant. Histopathological analysis revealed a lower median Ameho’s score in the RP group compared to the AC group, though without statistical significance.

Microbiota analysis showed no significant differences in alpha diversity across groups. However, beta diversity significantly differed in the AC group compared to Control, and after probiotic treatment, the RP group’s beta diversity showed a partial shift toward the Control group. Distinct microbial species characterized each group: Akkermansia spp. and Parasutterella spp. were predominant in distinguishing the Control group from others; Romboutsia spp. and Turicibacter spp. differentiated the AC group; and Roseburia spp. and Anaerotruncus spp. were the key species distinguishing the RP group from the others.

Conclusion

Multi-strain probiotics reduced TNF-α levels and modulated gut microbiota composition in DNBS-induced colitis. Although changes in IL-10, MDA, and histopathology were not statistically significant, trends favored the probiotic group. Microbial analysis revealed distinct species profiles across groups, with partial restoration of beta diversity and enrichment of beneficial taxa like Roseburia spp. in the probiotic group. These findings support the potential of probiotics as a therapeutic adjunct in IBD, highlighting the need for further studies to confirm efficacy and explore underlying mechanisms.

Clinical Case Summary

Case: A 23-year-old female patient presented with non-bloody diarrhea, abdominal pain, flatulence, postprandial fullness, bloating, nausea, anal pain and itching, and low back pain. Three years prior, a minor trauma led to an X-ray revealing a compression fracture of two lumbar vertebrae. A densitometric exam of bone tissue showed osteopenia (T-score = -1.2). The patient reported no harmful habits and no relevant family medical history. Physical exam revealed abdominal tenderness in the right and left pelvic regions. Laboratory abnormalities included CRP at 6.78 mg/L, fecal calprotectin >1000 µg/g, total IgA at 1.91 g/L, and Anti-tTG IgA at 406.1 RU/mL. Tests for intestinal infections were negative. An abdominal CT scan revealed terminal ileitis with mesenteric lymphadenopathy. Endoscopy showed multiple erosive lesions in the stomach (Helicobacter pylori negative), as well as multiple erosive lesions with fibrin coating in the ileum. Isolated erosive lesions were also noted in the transverse, descending, and sigmoid colons, and the lower ampullary section of the rectum. Histological patterns were consistent with both Crohn's disease (Montreal classification: A2, L3 + L4, B1p) and Celiac disease (Marsh classification: III B). The therapeutic approach was tailored to the patient’s condition: biological therapy (Infliximab), a gluten-free diet, bisphosphonates, calcium, and vitamin D supplementation.
Conclusion: Both Crohn’s and Celiac disease are primarily considered gastrointestinal (GI) disorders, but they are systemic conditions that may present with a broad range of extraintestinal manifestations. These may develop earlier than, or in the absence of, classic GI symptoms and may be the only indication of the underlying condition. Patients presenting with osteopenia, osteoporosis, or fractures may initially be evaluated for metabolic bone disorders, while underlying Crohn’s or Celiac disease remains undiagnosed and/or alters both diagnostic and therapeutic pathways.

References

1. Chong, K. W., & Ananthakrishnan, A. N. (2018). Extraintestinal manifestations of inflammatory bowel disease. World Journal of Gastroenterology, 24(42), 4757-4767.
2. Lebwohl, B., Sanders, D. S., & Green, P. H. (2018). Celiac disease. The Lancet, 391(10115), 70-81.
3. Aro, P., & Mustalahti, K. (2010). Extra-intestinal manifestations of celiac disease. Celiac Disease: From Pathogenesis to Treatment, 11-27.
4. O’Mahony, S., et al. (2012). Extra-intestinal manifestations of Crohn’s disease. World Journal of Gastroenterology, 18(32), 4091-4098.

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