Introduction

Previous antibiotic use influences the antibiotic resistance of H. pylori. However, the specific impact of prior clarithromycin use on the success of eradication therapies remains unclear.

Aims & Methods

The objective of this study was to examine the association between prior macrolide (particularly clarithromycin) consumption in the general population and the effectiveness of H. pylori eradication regimens in treatment-naïve patients.
A retrospective, observational, multicentre, and ecological study was conducted. Multivariate logistic regression was performed with the modified intention-to-treat effectiveness as the main outcome. Key variables included first-line clarithromycin-based treatments, therapy duration (7, 10, 14 days), proton pump inhibitor dose (low, standard, high), compliance (>90%), and clarithromycin consumption (defined daily doses/1,000 inhabitants/day, from the European Surveillance of Antimicrobial Consumption Network). Nested hierarchical models incorporated macrolide consumption, matched by year and country, and assessed the interaction between consumption and first-line empirical treatments from the European Registry on H. pylori Management (Hp-EuReg).

Results

The study included 27,549 naïve patients from 23 countries with macrolide consumption data from 2013 to 2022. Higher macrolide consumption, within 0 to 8 years before treatment was associated with reduced treatment effectiveness. The eradication rate consistently decreased as macrolide consumption increased, particularly within the previous four years. The efficacy of triple-clarithromycin-metronidazole, triple-clarithromycin-amoxicillin, and some bismuth-quadruple therapies containing clarithromycin decreased with higher macrolide consumption. The eradication rate decreased from 93% to 82% when clarithromycin consumption occurred 2 years before treatment. Table 1 presents the effects of macrolide consumption delays (0 to 8 years) on treatment effectiveness for each evaluated regimen, revealing consistent patterns among triple therapies with amoxicillin or metronidazole plus clarithromycin, though some variation was observed for quadruple therapies.

Conclusion

Higher macrolide consumption in the general population negatively impacts the effectiveness of first-line H. pylori clarithromycin-containing eradication treatments, with the effect decreasing after 5 years of exposure.

Disclosure

Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from: Mayoly, Allergan/Abbvie, Diasorin, Richen, Juvisé and Biocodex.
Olga P. Nyssen received research funding from: Mayoly, Allergan/Abbvie, Richen, Juvisé and Biocodex.

Introduction

Pregnancy is common in women with inflammatory bowel disease (IBD), a population in whom optimal obstetric management is essential to ensure maternal and neonatal well-being. Vaginal delivery is generally recommended as the preferred mode of birth due to its lower risk of complications and faster recovery. Unnecessary caesarean section (C-section) delivery increases the risk of maternal complications, such as infection and thrombosis, and may negatively impact neonatal outcomes, including respiratory distress and delayed breastfeeding. Identifying the precise prevalence of C-sections and the factors driving that prevalence in women with IBD is essential to improve care and promote safe, evidence-based delivery planning.

Aims & Methods

To assess the frequency of C-section, and to identify factors associated with the mode of delivery in pregnant women with IBD included in the DUMBO registry.
Patients from DUMBO registry, a prospective multicentre cohort study of pregnant women with IBD in Spain, were included. The registry systematically collects demographic characteristics, obstetric history, IBD phenotype and activity, treatments received during pregnancy, and pregnancy-related complications. Mode of delivery is recorded for all participants. In cases of C-section, investigators document whether the indication was obstetric or IBD-related, as well as the specific reason for the procedure. Logistic regression analysis was performed to identify clinical and disease-related variables independently associated with the likelihood of C-section.

Results

A total of 1,012 women had given birth at the time of data analysis; mean age 34 years (standard deviation 4.8); median IBD duration 8.8 years (interquartile range 4.5–13); 626 (57%) had Crohn’s disease (CD) (21% had perianal disease, 19% active), 216 (19%) had previous surgery due to IBD, 464 (42%) were exposed to biologics, and 122 (11%) had active disease during pregnancy. A total of 293 deliveries (29%) were by C-section. Among C-sections, 237 (81%) were indicated for obstetric reasons, and 56 (19%) for IBD. In univariate analysis, older maternal age, longer IBD duration, to have CD (vs. ulcerative colitis), prior IBD surgery, active perianal disease, and exposure to biologic therapy during pregnancy were significantly more frequent among patients undergoing C-section compared to those with vaginal delivery (table 1). In the multivariate analysis, older maternal age [Odds ratio (OR) = 1.05, 95% confidence interval (CI) = 1.02–1.08], biologic treatment during pregnancy (OR = 1.46, 95%CI 1.08–1.95), prior IBD surgery (OR = 1.47, 95%CI 1.47–2.95), and active perianal disease (OR = 4.89, 95% CI 1.86–12.8) were independently associated with a higher risk of C-section.

Conclusion

One-third of deliveries in women with IBD are by C-section (a figure higher than that in general population¹). In 20% of cases, the indication for C-section was directly related to IBD-specific conditions. Several factors associated with an increased risk of C-section were identified, which are also recognized as predictors of more severe disease. Further efforts are needed to assess the appropriateness of C-section indications and to reduce unnecessary procedures in women with IBD.

References

¹ Ministerio de Sanidad. Annual report on the National Health System of Spain 2023 [Internet]. Madrid: Ministerio de Sanidad; 2023 [accessed 2025 April 14]. p. 86. Available from: https://www.sanidad.gob.es/estadEstudios/estadisticas/sisInfSanSNS/tablasEstadisticas/InfAnualSNS2023/INFORME_ANUAL_2023.pdf

Disclosure

María José Casanova María José Casanova, has received education or research funding from Pfizer, Takeda, Janssen, MSD, Dr. Falk, Shire, Ferring, Galápagos, Abbvie and Lilly.
María Chaparro has served as speaker, consultant or research or education funding from MSD, Abbvie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Biogen, Gilead and Lilly.
Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma.
Cristina Calvino-Suarez, has served as a speaker for or has received research funding from MSD, AbbVie, Janssen, Takeda and Adacyte.
Pilar López Serrano has received grants from MSD, Abbvie, Takeda, Janssen, Faes, Ferring and Dr Falk Pharma.
Noemí Manceñido Marcos has served as a speaker and consultant for or received financial support for educational activities from Janssen, Abbvie, Pfizer, Takeda, Ferring, Faes Farma, Dr. Falk Pharma, and Tillots Pharma.
Marta Maia Boscá Watts Conflictos de interés: MSD, Ferring, Abbvie, Janssen, Biogen, Pfizer, Galápagos, Otsuka, Kern pharma y Takeda.
Agnès Fernández-Clotet has served as a speaker, or has recieves education funding from Dr. Falk, Janssen, Takeda, Chiesi and Pfizer.
Lara Arias García has served as speaker or has received research or education funding from MSD; Abbvie; Kern Pharma; Ferring; Faes Farma; Shire Pharmaceuticals; Pfizer; Takeda; Janssen; Tillots Pharma and OtsuKa Pharmaceutical.
Lucía Marquez-Mosquera has been served as speaker and / or has received research or education funds from Abbvie, Pfizer, Takeda, Janssen.
Marta Calvo Moya has served as a speaker, consultant and advisory member for or has received research funding from MSD, Abbvie, Takeda, Jannsen, Pfizer, Lilly, Mylan, Kern Pharma, Ferring, Shire Pharmaceuticals, Tillots, Dr. Falk Pharma, Chiesi, and Gebro Pharma.
Miriam Mañosa has served as a speaker, consultant and advisory member for or has received research funding from AbbVie, Janssen, MSD, Pfizer, Faes, Takeda, Tillots, Ferring.
Vicent Hernández has served as consultant, has served as speaker, has received travel support or research funding from MSD, AbbVie, Ferring, Dr. Falk Pharma, Tillotts Pharma, Pfizer, Takeda, Janssen, KernPharma Biologics, Adacyte, Sandoz, Biogen, Fresenius-Kabi, FAES Farma and Galapagos.
Raquel Camargo-Camero, He recibido financiación para diferentes tipos de actividades formativas de Janssen, Ferring, Abbvie, Falk, Pfizer, Galápagos y Takeda.
Iván Guerra has served as speaker or has received education funding from Takeda and Tillots.
David Busquets declares educational activities, research projects and scientific meetings sponsored by Abbvie, Janssen, Ferring, Pfizer, Tillots Pharma and Takeda.
Montserrat Rivero has served as a speaker or advisory member from TaKeda, Janssen, Galapagos, Ferring and Pfizer.
Iago Rodríguez-Lago has received financial support for traveling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Celltrion, Chiesi, Danone, Ferring, Faes Farma, Janssen, Galapagos, MSD, Pfizer, Roche, Takeda, and Tillotts Pharma. Financial support for research: Tillotts Pharma.
Rest of authors have nothing to declare.

Introduction

Small intestinal bacterial overgrowth (SIBO) is a clinical syndrome with abdominal complaints and malabsorption. Despite concerns over cure rates, recurrence, and antibiotic resistance, rifaximin (RIF) remains the primary treatment. Berberine (BBR), an affordable traditional medicine, has demonstrated gut microbiota modulation, making it a promising alternative.

Aims & Methods

We conducted an open-label, non-inferiority randomized controlled trial (BRIEFSIBO) comparing BBR and RIF in SIBO patients. Patients were randomly assigned to receive either RIF or BBR. The primary outcome was breath test (BT) conversion to negative, with symptom scores and the Bristol stool scale as secondary outcomes.

Results

A total of 186 patients completed the study. No significant baseline differences were found between groups in age, gender, BMI, smoking, or alcohol use. BBR demonstrated non-inferior efficacy to RIF for primary outcome (BT eradication) at Week 2 (ITT: BBR 45%, RIF 51%, Z=2.407, P=0.008; PP: BBR 44%, RIF 47%, Z=2.4787, P=0.007) and Week 6 (ITT: BBR 53%, RIF 44%, Z=4.3244, P<0.001; PP: BBR 54%, RIF 45%, Z=4.077, P<0.001). What's more, BBR demonstrated non-inferior efficacy to RIF for secondary outcome (clinical improvement) at Week 2 (ITT: BBR 68%, RIF 75%, Z=2.9209, P=0.0017; PP: BBR 73%, RIF 72%, Z=3.3531, P=0.0004) and Week 6 (ITT: BBR 75%, RIF 80%, Z=2.8514, P=0.0022; PP: BBR 81%, RIF 86%, Z=3.0747, P=0.0011). Following a four-week period of discontinuation, the rate of combined expiratory and symptomatic relapse in patients treated with RIF was 8.57%. In contrast, no such relapses were observed in patients treated with BBR. BT values at 60–90 minutes and AUC decreased in both groups, though RIF showed recurrent peak values during follow-up. A novel breath peak acceleration parameter, reflecting local gut gas load, decreased in both groups. BBR significantly improved bloating at Week 6, whereas RIF improved bowel movement frequency. At Week 6, patients were classified into response, relapse, and nonresponse groups to identify optimal candidates for each drug. RIF responders showed significant improvement in bloating and bowel-related symptoms (P<0.05). Baseline gut microbiota analysis revealed significant β diversity differences between three groups in BBR but not in RIF. Genus-level microbiota composition differed between responders, with BBR responders exhibiting higher baseline proportions of Phascolarctobacterium, Klebsiella, and Haemophilus, and lower Coprobacter. At Week 6, both groups showed enriched Bacteroides, while BBR responders had elevated Phascolarctobacterium, Streptococcus, and Haemophilus, with lower Bifidobacterium.

Conclusion

BBR is non-inferior to RIF for SIBO treatment and offer a promising and cost-effectiveness new option.

References

1. Pimentel M, Saad RJ, Long MD, et al. ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth. Am J Gastroenterol 2020;115(2):165-78. doi: 10.14309/ajg.0000000000000501
2. Bushyhead D, Quigley EMM. Small Intestinal Bacterial Overgrowth-Pathophysiology and Its Implications for Definition and Management. Gastroenterology 2022;163(3):593-607. doi: 10.1053/j.gastro.2022.04.002
3. Quigley EMM, Murray JA, Pimentel M. AGA Clinical Practice Update on Small Intestinal Bacterial Overgrowth: Expert Review. Gastroenterology 2020;159(4):1526-32. doi: 10.1053/j.gastro.2020.06.090
4. Leite G, Rezaie A, Mathur R, et al. Defining Small Intestinal Bacterial Overgrowth by Culture and High Throughput Sequencing. Clin Gastroenterol Hepatol 2024;22(2):259-70. doi: 10.1016/j.cgh.2023.06.001
5. Svedlund J, Sjödin I, Dotevall G. GSRS--a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci 1988;33(2):129-34.
6. Liu ZJ, Wei H, Duan LP, et al. [Clinical features of irritable bowel syndrome with small intestinal bacterial overgrowth and a preliminary study of effectiveness of Rifaximin]. Zhonghua Yi Xue Za Zhi 2016;96(24):1896-902. doi: 10.3760/cma.j.issn.0376-2491.2016.24.005
7. Guo H, Lu S, Zhang J, et al. Berberine and rifaximin effects on small intestinal bacterial overgrowth: Study protocol for an investigator-initiated, double-arm, open-label, randomized clinical trial (BRIEF-SIBO study). Front Pharmacol. 2023;14:1121435. doi:10.3389/fphar.2023.1121435

Introduction

Management of perianal fistulas in Crohn’s disease (CD) is challenging and requires a multidisciplinary approach, combining surgical drainage and biologic therapies, such as infliximab (IFX). Higher IFX trough concentrations have been associated with improved fistula healing rates. The subcutaneous (SC) formulation of IFX achieves 2–3 times higher and more stable trough levels compared to intravenous (IV) formulation. This study hypothesizes that SC IFX could enhance perianal fistula healing rates in CD patients.

Aims & Methods

REMSILAP study is part of the 3TLAP cohort, a French prospective multicenter observational study evaluating optimal therapeutic strategies for achieving clinical and radiological remission of perianal fistulas in CD at 12 months post-surgical drainage. The REMSILAP substudy focuses specifically on patients receiving SC IFX. Patients who received SC IFX after or within six months prior to surgical drainage were included. Baseline was defined as the day of surgical drainage. The primary outcome was the proportion of patients achieving complete clinical remission defined as Perianal Disease Activity Index (PDAI) fistula drainage subscore = 0 associated with PDAI activity restriction subscore <3 and absence of seton, and radiological remission at 12 months. Here, we present preliminary findings from REMSILAP.

Results

Among the 353 patients enrolled in the 3TLAP cohort, 54 were included in REMSILAP. The cohort consisted of 61.1% male patients, with a median age of 36 years and a median disease duration of 4.5 years. Penetrating disease (B3 phenotype) was present in 40.7%, and 33.3% had a history of surgical resection. At baseline, 40.7% of patients had quiescent disease regarding Harvey-Bradshaw index, while 5.6% had severe disease activity. Biologic exposure prior to inclusion was noted in 42.6%. Surgical drainage, with seton placement, was performed in 74.1% of patients. Forty-eight patients (88%) initiated SC IFX treatment after surgical drainage. Of the patients receiving SC IFX, 50% transitioned to SC IFX after less than three IV infusions. Among those on IV IFX at baseline, 20.4% were receiving a 10 mg/kg dose. Forty-three patients (79.6%) received SC IFX in combination with immunomodulators (azathioprine, methotrexate, or 6-mercaptopurine). The median duration of SC IFX treatment was 13.1 months, with treatment maintained for 67.5% of the follow-up period (mean: 19.3 ± 11.3 months). Forty-three patients (79.6%) were treated with a stable dose of 120 mg/14 days and 6 patients (11.1%) had an intensification of SC IFX dosage to 120mg / 7 days. At 12 months, 42 patients were evaluable for clinical outcomes. Complete clinical healing at 12 months was achieved in 11 patients (27.5%) and association of PDAI restriction subscore <3 and drainage subscore = 0 was found in 18 patients (42.9%). Thirteen patients (34.2%) from the 25 patients who had received at least 6 months of SC IFX treatment showed clinical healing at 6 months. Out of the 26 patients treated with at least 12 months of SC IFX treatment, clinical healing was achieved in 16 patients (61.5%) at 12 months. Among the 11 patients with clinical healing at 12 months, 8 (72.2%) were treated with SC IFX treatment following more than three IFX IV infusions. None of the 11 patients with available MRI date showed radiological healing at 12 months.

Conclusion

Subcutaneous infliximab following surgical drainage of Crohn’s disease perianal fistula demonstrates high treatment persistence and promising rates of fistula healing.

Disclosure

This study was funded by Celltrion Healthcare France