Introduction

The effectiveness of first-line treatment for H. pylori infection varies between countries. Local data are necessary to guide clinical practice. We aimed to assess the effectiveness of first-line eradication treatments for H. pylori in Israel.

Aims & Methods

International, multicenter, prospective, non-interventional registry aiming to evaluate the decisions and outcomes of H. pylori management by European gastroenterologists (Hp-EuReg). All infected adult patients treated with a first-line therapy at 10 centers in Israel between 2013 and 2023 were registered at e-CRF AEGRedCap and were included in the current study. Effectiveness was assessed by modified intention-to-treat (mITT) and per-protocol (PP) analyses.

Results

Table: Empirical first-line therapy effectiveness by modified intention-to-treat and per-protocol analyses, by treatment duration and acid inhibition in Israel
	Use, n (%)	mITT Success n/N (%)	PP Success n/N (%)
Treatment scheme
Triple-C+A Sequential-C+A+T Quadruple-C+A+T Quadruple-C+A+M	49 (16.1) 20 (6.6) 132 (43.3) 38 (12.5)	36/44 (81.8) 17/19 (89.5) 73/86 (84.9) 13/13 (100)	36/44 (81.8) 17/19 (89.5) 71/80 (88.8) 13/13 (100)
Treatment Duration
7 days 10 days 14 days	22 (7.3) 68 (22.4) 213 (70.3)	16/20 (80) 43/50 (86) 92/111 (82.9)	16/20 (80) 42/49 (85.7) 88/102 (86.3)
Potency of acid inhibition*
Low Standard High	63 (20.6) 12 (3.9) 231 (75.5)	48/58 (82.8) 6/6 (100) 105/125 (84)	47/57 (82.5) 6/6 (100) 101/116 (87.1)
Overall	320 (100)	160/191 (83.8)	155/181 (85.6)
Abbreviations: n: total number of patients analysed; mITT, modified intention to treat; PP, per-protocol; C, clarithromycin; A, amoxicillin; T, tinidazole; M, metronidazole; *Low dose PPI – 4.5 to 27 mg omeprazole equivalents. b.i.d.; standard dose PPI – 32 to 40 mg omeprazole equivalents. b.i.d.; high dose PPI – 54 to 128 mg omeprazole equivalents. b.i.d.

A total of 663 cases were registered, where 320 (48%) had received a 1^st line empirical therapy with an average age of 51±18 years and 183 (57%) were females. The most common indication for H. pylori investigation was dyspepsia (67%). Infection was diagnosed with histology (56%), ¹³C-Urea breath test (22%), rapid urease test (17%) and monoclonal stool Ag test (5.3%). Quadruple concomitant therapy with PPI-clarithromycin-amoxicillin-tinidazole was the most frequent 1^st line treatment (43%), mostly prescribed for 14 days (87% of the patients) and with high-dose PPIs (91% of the cases), followed by triple therapy with PPI-clarithromycin-amoxicillin (16%) and quadruple concomitant therapy with PPI-clarithromycin-amoxicillin-metronidazole (12%). The majority of prescriptions were of 14-day (70%) length, followed by 10-day (22%) and 7-day (7.3%) duration. High potency proton pump inhibition (PPI) was prescribed to most patients (75%). Overall treatment success was 84% (160/191) and 86% (155/181) by mITT and PP, respectively, with the highest effectiveness provided by 10-day and high-dose PPIs of sequential therapy with clarithromycin-amoxicillin-tinidazole (89.5% by mITT), and by 14-day and high-dose PPIs of concomitant therapy with clarithromycin-amoxicillin-tinidazole (85% by mITT). Longer treatment durations and higher PPI doses provided better cure rates. Treatment effectiveness did not change significantly during the study period, and remained suboptimal (<90%) over the years. Compliance (>90% drug intake) was 97%. The incidence of at least one adverse event was reported in 10%, necessitating treatment cessation in 1.5%.

Conclusion

In Israel, empirical first-line treatment for H. pylori eradication is still suboptimal (<90%). Treatments should consist of four drugs and should be optimised with a 14-day duration and standard/high doses of PPIs.

Disclosure

None

Introduction

There are doubts about the effectiveness of concomitant use of probiotics (PB) in the treatment of Helicobacter pylori infection. Objective: To determine whether the use of PB improves the effectiveness of eradication treatments used in Europe.

Aims & Methods

Prospective, multicentre, non-interventional, prospective registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Data were collected in an e-CRD in AEG-REDCap from 2013 to 2021. All data from countries with at least 30 cases undergoing eradication therapy and at least 1 with associated PB were included, using patients without PB as controls and grouping by geographical region. Modified intention-to-treat (mITT) analyses were performed, as well as multivariate analysis, assessing factors associated with treatment effectiveness.

Results

36,699 patients were included, 8,233 (22%) with PB. Overall, PB use was associated with greater effectiveness (91% vs 86%; p<0.0001). Adjusting for treatment regimen, this significance held for triple (89% vs 83%; p<0.0001), concomitant quadruple (93% vs 89%; p=0.0009), quadruple with bismuth (92% vs 86%; p<0.0001) and sequential (91% vs 78%; p<0.0001) therapies. In the logistic regression model in first-line eradication (adjusted for age, sex, duration of eradication treatment, PPI dose and adherence), PB use maintained the benefit in the triple, bismuth quadruple and sequential treatments. After adjusting such a model by region, significance was maintained in the Eastern region (low rate of resistance to clarithromycin and metronidazole) for triple therapies, and in the Central region (high rate of resistance) for concomitant quadruple and sequential therapies.

Conclusion

In Europe, the use of formulations with PB adjuvant to eradication therapy is associated with increased effectiveness of eradication therapy, with the benefit being superior in triple and sequential therapies.

Disclosure

Nothing to disclosure

Introduction

​Gastric lesions associated with Helicobacter pylori, eradication issues and problems of its sometimes-insufficient effectiveness continue to remain one of the most pressing topics in modern healthcare.

Aims & Methods

The analysis aimed to assess the usage, efficacy, and safety of initial empirical treatment for H. pylori infection in Azerbaijan.
​Data were collected at e-CRF AEG-REDCap from the European Registry on Helicobacter pylori Management (Hp-EuReg) and quality reviewed from January 2020 to May 2023. All treatment-naïve cases were assessed for effectiveness by modified intention-to-treat (mITT), per-protocol (PP) analyses, and a separate multivariate analysis was performed.

Results

The study included 3,898 patients (67% reported dyspepsia). In 1.9% of patients, at least one type of allergy was reported (1.6% to penicillin). A total of 226 patients (5.8%) received concurrent medication: PPI (5.1% on demand, 0.1% daily), aceltylsalicylic acid (1.2% on demand, 0.2% daily), NSAIDs (1.3% on demand), statins (1.2% on demand, 0.1% daily). The most frequent indication for treatment was dyspepsia with normal endoscopy in 2,610 patients (67%). In total, 3,853 (99%) patients were diagnosed pre-treatment using the rapid urease test, which was the most frequently used. The following tests were likewise used in a lower number of cases: monoclonal stool antigen test (MSAT)(0.7%) and polyclonal stool antigen test (0.1%). In 2,661 (68%) cases a MSAT was used, being the most frequent post-treatment confirmation method. Additionally, in 55 (1.4%) cases an invasive method, that is endoscopy, was performed, to confirm the eradication. First-line empirical treatment prescriptions and mITT effectiveness by treatment schemes is presented in Table 1.
Triple regimens were the most frequently prescribed in over 3,000 (82%) patients, where the PPI-C+A treatment scheme represented 54% of the total of first-line prescriptions. Treatment length varied from 14 days in 56% of cases, 10 days in 27%, and 7 days in 17%. Following 14-day treatments prescriptions achieved optimal (>90%) mITT effectiveness: PPI-C+A (94%), PPI-C+M (97%), PPI-C+M+ B (96%) and PPI-C+A+B (98%). Following schemes also provided optimal results when combined with standard-dose (i.e., 40 mg omeprazole equivalent twice a day) PPIs: PPI-A+Tc (100%) and PPI-C+A+B (96%). Additionally, prescriptions concomitantly administered with high-dose (i.e., 80 mg omeprazole equivalent twice a day) PPIs provided also over 90% eradication rates: PPI-C+A (94%), PPI-C+M (97%), PPI-C+M+B(100%) and PPI-C+A+B (99%). Compliance with treatment was over 90% in the vast majority of cases. The incidence of at least one adverse event was reported in 12% of cases.
Table 1. Most frequent first-line empirical treatment prescriptions and modified intention-to-treat effectiveness in Azerbaijan.

A-amoxicillin, C- clarithromycin, M- metronidazole, L- levofloxacin, Tc- tetracycline, B - bismuth			mITT- modified Intention-to-treat;	PP: per protocol analysis;	low-dose PPI, between 4.5 and 27 mg omeprazole equivalents given twice a day;	standard-dose PPI, between 32 and 40 mg omeprazole equivalents given twice a day;	high-dose PPI, between 54 and 128 mg omeprazole equivalents given twice a day; NA: not available data.
Treatment	Number of prescriptions	Use (%)	mITT, N (%)	PP, N (%)	mITT, N (%) Low-dose PPI	mITT, N (%) Standard-dose PPI	mITT, N (%) High-dose PPI
Triple-C+A	2,117	54.3	1,832 (91,2%)	1,819 (95.2%)	873 (91.2%)	527 (89.3%)	420 (93.8%)
Triple-C+M	760	19.5	584 (93,3%)	581 (96.5%)	326 (93.4%)	89 (86.4%)	167 (97.1%)
Quadruple-C+A+B	610	15.6	579 (98%)	574 (99.8%)	219 (98.2%)	187 (96.4%)	178 (99.4%)
Triple-A+L	159	4.1	124 (82,1%)	124 (99.2%)	52 (82.5%)	68 (81.9%)	4 (80.0%)
Triple-A+Tc	75	1.9	71 (94,7%)	71 (100.0%)	28 (93.3%)	43 (95.6%)	NA
Quadruple-C+M+B	44	1.1	40 (95,2%)	40 (100.0%)	26 (100.0%)	6 (75.0%)	8 (100.0%)
Other	44	1.1	114 (90,5%)	113 (97.4%)	55 (93.2%)	55 (90.2%)	4 (66.7%)
Total	3,809	97.6	3,344 (92.4%)	3,322 (96.6%)	68 (92.5%)	975 (89.9%)	776 (95.4%)

Conclusion

The prescribed H. pylori eradication regimens during the period 2020–2023 in Azerbaijan adhered only partially to the Maastricht VI recommendations; however, most of first-line empirical therapies achieved high (≥90%) cure rates, providing a good safety profile.

Introduction

The link between the misuse in global antibiotic consumption and increased antimicrobial resistance is well documented. Clarithromycin-based anti-H. pylori eradication therapy as a triple regimen (encompassing a PPI plus two antibiotics) has been used empirically worldwide without antimicrobial susceptibility testing. In the last decade, a marked decreased in the effectiveness of clarithromycin-based regimens has been observed globally.

Aims & Methods

This study aimed at exploring the potential relationship between the consumption of macrolides in the overall population as a factor influencing the effectiveness of H. pylori clarithromycin-containing regimens.
Data from the European Registry on Helicobacter pylori management (Hp-EuReg) were used for this analysis. A multivariate logistic regression was built using the modified intention-to-treat (mITT) effectiveness analysis as the outcome and the following main effects: first-line treatment scheme (using the 10 most frequent antibiotic combinations), duration of treatment (as 7, 10 or 14-day lengths), proton-pump inhibitor (PPI) dose (categorised as low, standard, or high; that is, 20 mg, 40 mg or 80 mg omeprazole equivalent twice a day), compliance (that is, >90% of drug intake), and clarithromycin consumption expressed as daily doses per 1,000 inhabitants per day. Data of macrolide community consumption was taken from the European Surveillance of Antimicrobial Consumption Network (ESAC-Net). Hierarchical nested models were constructed by adding macrolide consumption, matching by year and country with the corresponding patients’ therapy, and the interaction between consumption and treatment scheme (taken from the Hp-EuReg).

Results

In total, 28,590 first-line treated patients from 24 European countries participating in the Hp-EuReg, on which data of macrolides consumption in the period 2013-2022 was available, were evaluated. Three nested models were analysed: the first one with the main effects without including macrolides consumption (A), the second with the full set of main effects (including macrolides consumption) (B) (likelihood ratio test A-B p-value=2.11.10^-2), and the third one included both macrolides consumption and interactions between this main effect and treatments (C) (likelihood ratio test B-C p-value=4.08 10^-10). Model B (without interactions) showed a global decrease in treatment mITT effectiveness (OR: 0.95 [0.91-0.99]). Model C (with interactions) showed a significant decrease in the mITT effectiveness in three different treatments (Table): triple-clarithromycin-metronidazole (OR: 0.37 [0.25-0.53]), triple-clarithromycin-amoxicillin (OR: 0.60 [0.43-0.82]), and sequential-clarithromycin-amoxicillin-metronidazole/tinidazole (OR: 0.60 [0.43-0.84]); whereas, bismuth quadruple therapy (single capsule) remained unaffected.

Table. Multivariate logistic regression (model C) evaluating the interaction between clarithromycin consumption and first-line empirical treatment effectiveness (by modified intention-to-treat) in Europe between 2013 and 2022.
OR: odds ratio; CI: confidence interval; *low dose PPI – 4.5 to 27 mg omeprazole equivalents. b.i.d.; standard dose PPI – 32 to 40 mg omeprazole equivalents. b.i.d.; high dose PPI – 54 to 128 mg omeprazole equivalents. b.i.d.; A: amoxicillin; B: bismuth; C: clarithromycin; L: levofloxacin; M: metronidazole: tetracycline.; **Three-in-one single-capsule containing metronidazole. tetracycline and bismuth; C cons: clarithromycin consumption.
	OR	95% CI	p-value
Intercept	0.42	0.15-1.22	0.17
Compliance (>90% of drug intake)	7.41	6.30-8.71	1.01e-92
10 days prescriptions ​14 days prescriptions	0.92 1.06	0.92-1.04 0.94-1.21	0.25 0.43
Standard-dose PPI * ​High-dose PPI*	1.58 1.79	1.44-1.74 1.65-1.95	1.08e-15 7.23e-31
Triple- PPI+C+A ​Triple- PPI+C+M ​Triple- PPI+A+M ​Triple- PPI+A+L ​Conco- PPI+C+A+T/M ​Seq- PPI+C+A+T/M ​Quadruple- PPI+C+A+B ​Quadruple- PPI+single capsule** ​Other	2.32 3.95 1.90 1.29 1.97 4.71 0.99 2.32 1.45	0.80-6.34 1.25-11.93 0.64-5.43 0.36-4.40 0.68-5.42 1.55-13.66 0.21-4.88 0.76-6.69 0.47-4.22	0.18 0.04 0.32 0.74 0.28 0.02 0.99 0.20 0.58
C cons ​Triple- PPI+C+A: C cons ​Triple- PPI+C+M: C cons ​Triple- PPI+A+M: C cons ​Triple- PPI+A+L: C cons ​Conco- PPI+C+A+T/M: C cons ​Seq- PPI+C+A+T/M: C cons ​Quadruple- PPI+C+A+B:C cons ​Quadruple-PPI+Single capsule**: C cons ​Other: C cons	1.42 0.60 0.37 0.71 0.76 0.76 0.60 0.89 0.86 0.72	1.04-1.96 0.43-0.82 0.25-0.53 0.49-1.01 0.51-1.12 0.54-1.04 0.43-0.84 0.52-1.48 0.60-1.20 0.51-1.00	0.07 0.01 1.58e-05 0.11 0.24 0.15 0.01 0.72 0.46 0.10

Conclusion

The models showed an inverse association between the clarithromycin consumption and empirical first-line therapy overall effectiveness in Europe; particularly, in those clarithromycin-containing regimens. Further research will consider a broader time lag to assess this association.

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

It is not yet clear what is the best first-line empirical therapy in patients with Helicobacter pylori (H. pylori) infection. For this reason, it is important to constantly monitor the effectiveness of the different therapies used in clinical practice.

Aims & Methods

The aim of this study was therefore to assess the effectiveness of empirical first-line treatment prescribed in Italy evaluating the European Registry on H. pylori Management (Hp-EuReg). The Hp-EuReg is an international multicentre prospective non-interventional registry recording information on H. pylori infection management since 2013. All infected adult patients enrolled were systematically registered at AEG-REDCap e-CRF. Data of all H. pylori-positive treatment-naïve patients enrolled from 2013 to December 2023 by Italian centres participating in the Hp-EuReg, were extracted, subject to quality control, and analysed. The effectiveness of the first-line treatment empirically prescribed was evaluated according to the modified intention-to-treat (including all patients that completed follow-up, i.e., a confirmatory test of success or failure available after eradication treatment), and per-protocol analysis (including all patients that completed follow-up and took at least 90% of the treatment drugs).

Results

In total, 4,144 patients were included for analysis; the mean age was 52 years (SD ± 5), and 60% of patients were women. Overall, 1.0% of the cases were allergic to penicillin. Among those non-allergic to penicillin, 10-day sequential therapy (mainly as PPI-clarithromycin-amoxicillin-tinidazole) was most commonly prescribed (54%), followed by 10-day single capsule bismuth quadruple therapy with metronidazole and tetracycline (19 %), and 10 or 14-day non-bismuth concomitant treatment (mainly as clarithromycin-amoxicillin-tinidazole) (9.3%), providing these regimens optimal cure rates (91.5%, 95.5%, 92% and 97%; respectively). Additional first-line prescriptions encompassed 7, 10 or 14-day triple therapy with PPI-clarithromycin-amoxicillin (5.5%), and 10-day triple therapy with PPI- -levofloxacin-amoxicillin (2.9%) (see Table 1).

Table 1; Effectiveness by modified intention-to-treat (mITT), and per-protocol (PP) analyses of first-line empirical treatment in patients not allergic to penicillin enrolled in the Italian centres participating in the European Registry on H. pylori management (Hp-EuReg).

mITT: modified intention-to-treat; PP, per protocol; A, amoxicillin; B, bismuth salt; C, clarithromycin; L, levofloxacin; M, metronidazole; PPI, proton pump inhibitor; T, tinidazole; Tc, tetracycline.
First-line treatment	Length (days)	mITT % (95% CI)	PP % (95% CI)
Sequential (PPI + C-A-T/M)	10	91.5 (90.2 to 92.7)	90.9 (89.5 to 92.1)
PPI + Single capsule (M+Tc+B)	10	95.5 (93.7 to 96.8)	96.6 (94.9 to 97.7)
Concomitant (PPI + C-A-M/T)	10	92.2 (86.6 to 95.6)	93.5 (88.1 to 96.5)
	14	96.6 (93.6 to 98.4)	98.1 (95.6 to 99.2)
Triple PPI-C-A	7	83.6 (72.9 to 90.6)	86.2 (75.7 to 92.5)
	10	80 (71.1 to 86.7)	80.4 (71.4 to 87.1)
	14	100 (0.77 to 100)	100 (0.77 to 100)
Triple PPI-A-L	10	81.4 (72.7 to 87.7)	82.8 (74.2 to 89)

Conclusion

Among the first-line empiric treatments prescribed by the Italian centres participating in the Hp-EuReg, only single-capsule bismuth quadruple therapy with metronidazole-tetracycline-bismuth, sequential therapy with clarithromycin-amoxicillin-tinidazole, and non-bismuth concomitant therapy with clarithromycin-amoxicillin-tinidazole, achieved over 90% effectiveness.

Disclosure

Olga P. Nyssen received research funding from Mayoly and Allergan; Antonio Gasbarrini served as consultant for Abbvie, Actial, Alpha-Sigma, Eisai, Gilead, Malesci; Maria Pina Dore received funding from Sanofi, Takeda; Alfredo Di Leo served as a consultant for THD SpA; Gerardo Nardone received research grant from Sofar S.p.a and Alfasigma; Francis Mégraud received research grant from Allergan, bioMerieux, Mobidiag (to the institution), and as speaker from Biocodex and Mayoly; Claudio Borghi served as speaker, consultant, and advisory member for Servier, Novo‐Nordisk, Astra‐Zeneca,Sanofi; Javier P. Gisbert served as speaker, consultant, and advisory member for or received research funding from Mayoly, Allergan, Diasorin, GebroPharma, and Riche.