Comparative efficacy and safety of high-dose dual therapy, bismuth-based quadruple therapy and non-bismuth quadruple therapies for Helicobacter pylori infection: a network meta-analysis

Abstract

Helicobacter pylori (H. pylori) infection is associated with the development of multiple diseases. The eradication rate of H. pylori has gradually decreased, suggesting the need to discover more effective therapies. This study aimed to compare the effectiveness of first-line treatments including high-dose dual therapy (HDDT), bismuth-based quadruple therapy (BQT), sequential therapy (ST), concomitant therapy (CT) and hybrid therapy (HT) by network meta-analysis (NMA). A comprehensive search on PubMed, Embase, Cochrane Library and Web of Science, was performed from their inception to 1 September 2019. A network analysis of randomized controlled trials (RCTs) comparing first-line therapies were carried out using Stata 14.0 and Revman 5.2. Moreover, a sensitivity analysis was conducted by omitting non-Asian studies. Finally, 41 RCTs with 14 119 patients were included. The NMA showed that, in terms of eradication rate, ST for 10 days (ST-10) was significantly lower than CT for 10 or 14 days (CT ≥ 10). Sensitivity analysis among the Asian population showed that ST-10 denoted the lowest effectiveness among the interventions. The ranking results based on probability showed that HDDT ranked first for the eradication rate. As for adverse events, HDDT was significantly less than BQT and CT regardless of duration, while BQT for 14 days represented higher adverse events than ST, HT and CT ≥ 10. HDDT ranked first among the therapies. In conclusion, HDDT for 14 days appeared to be the most optimal first-line therapy for H. pylori among the Asian population with comparable efficacy and compliance but causing fewer adverse events.

Effectiveness and Safety of High-Dose Dual Therapy: Results of the European Registry on the Management of Helicobacterpylori Infection (Hp-EuReg)

“…Two network meta-analyses also explored the eradication rates of different first-line treatment regimens [ 19 , 27 ]. One of them included 41 RCTs comparing mainly concomitant and sequential therapy but also reverse hybrid therapy, as well as different bismuth-based quadruple therapies, where five studies included a HDDT arm.…”

“…One of them included 41 RCTs comparing mainly concomitant and sequential therapy but also reverse hybrid therapy, as well as different bismuth-based quadruple therapies, where five studies included a HDDT arm. The results of this meta-analysis suggested that 14-day HDDT was the preferred first-line treatment in the Asian population [ 27 ]. Another network meta-analysis (68 studies, three of them with an HDDT arm) showed that HDDT was more effective than bismuth-based triple and quadruple therapies but less effective than non-bismuth concomitant, sequential, and reverse hybrid quadruple treatments, levofloxacin-containing therapy, and vonoprazan-triple therapy [ 19 ].…”

“…In fact, one of the network meta-analyses places HDDT in the worst place in terms of compliance compared to bismuth-based, concomitant, and sequential quadruple therapies. HDDT is last in compliance in both total patients and in the Asian population sub-analysis [ 27 ].…”

“…The 60 patients included in our study, mostly registered in Spain, were treated with 3 g of amoxicillin per day divided into three doses, and most of them, plus a high-dose PPI regimen [ 15 , 16 ], also distributed in three doses for 14 days. This is a very different scenario from the RCTs and meta-analyses, which deal with a high number of patients and strict inclusion and exclusion criteria [ 8 , 9 , 10 , 19 , 27 ]. The main limitations of our study are the reduced number of patients and the inevitable variability in terms of the number and treatment regimens received before HDDT, reflecting clinical practice.…”

High-dose dual therapy versus bismuth-containing quadruple therapy for the treatment of Helicobacter pylori infection – A review of the strengths, weaknesses, and proposed solutions

“…In another meta-analysis (2020), HDDT was equivalent to the recommended first-line or rescue regimens (triple therapy, BCQT, and non-bismuth quadruple therapy) with fewer side effects [ 42 ]. Similarly, by a network meta-analysis (2021), HDDT for 14 days appeared to be the most optimal primary therapy for H. pylori among Asian populations with comparable efficacy and compliance and causing fewer side effects [ 43 ].…”