Introduction
The efficacy of Helicobacter pylori (H. pylori) eradication regimens containing a proton pump inhibitor (PPI) plus antibiotics has gradually declined in recent years due to higher rates of antimicrobial resistance and insufficient acid inhibition. Vonoprazan (VPZ) is a novel potassium-competitive acid blocker which provides a stronger and longer-lasting effect on gastric acid suppression than PPIs. Our objective was to perform a systematic review and meta-analysis evaluating the efficacy and safety of VPZ for H. pylori eradication.
Aims & Methods
We conducted bibliographical searches in PubMed, Embase and the Cochrane Library up to April 2023. Selection: studies evaluating the use of VPZ in the eradication treatment. Outcomes: Efficacy was assessed by intention-to-treat analysis. Safety was also evaluated. Results were combined by meta-analysing risk differences (RD) and were stratified by dual, triple and quadruple therapy, first-line and rescue therapy, and by the presence of clarithromycin resistance.
Results
Overall, 75 studies were included, evaluating 44,992 patients, where 22,264 had received VPZ and 22,658 a PPI-based eradication therapy. The overall eradication rate with VPZ was 88% (95%CI=87-90%, 75 studies, I2=88%). When only RCTs were considered, similar results were obtained (87%, 95%CI=85-90%, 35 studies I2=84%).
When comparing dual, triple and quadruple VPZ-containing therapies, a tendency towards better efficacy with those regimens using a greater number of antibiotics was observed: 85%, 88% and 95%, respectively. However, when we compared the eradication rates between VPZ-based dual vs. triple regimens, no significant differences were reported, either in the overall analysis (P=0.17) or in the meta-analysis of studies directly comparing these regimens (P=0.21).
The eradication rate with VPZ-based therapy in first-line was 87% (95%CI=86-89%, 55 studies, I2=89%), and 90% (95%CI=87-93%, 37 studies, I2=84%) when used as rescue therapy. Among treatment-naïve patients, a significant superiority in the VPZ vs. PPI-based regimens was reported (87% vs. 70% respectively; RD=0.12, 95%CI=0.10-0.14, P<0.00001, I²=83%). However, no significant differences were shown between VPZ and PPIs when used in rescue therapy. When focusing on RCTs only, similar results were obtained.
Among those patients with clarithromycin-resistant strains, an overall efficacy of VPZ-based therapies was 81% (95%CI=75-85%, 18 studies, I2=60%), while in those with clarithromycin-susceptible strains it was 92% (95%CI=89-95%, 18 studies, I2=87%). We found a significant superiority of VPZ vs. PPIs (75% vs. 39%; RD=0.35, 95%CI=0.27-0.42, P<0.00001, 7 studies, 797 patients) in clarithromycin-resistant patients; whereas no significant differences were found in the clarithromycin-susceptible group. RCTs subgroup analysis showed similar results.
The overall incidence of adverse events with VPZ was 18% (95%CI=15-20%, 69 studies, I2=97%). No significant differences were found between VPZ and PPIs regimens tolerability.
Conclusion
The efficacy of VPZ-based regimens was over 85% in all treatments evaluated. The advantage of triple over dual VPZ could not be demonstrated in direct comparisons. In treatment-naïve patients as well as in those cases with clarithromycin-resistant strains, VPZ-based regimens performed better than PPIs-based ones; however, in rescue therapy and in clarithromycin-susceptible patients, this advantage was not confirmed. Tolerability was similar in both VPZ and PPIs regimens.
Disclosure
Dr. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from Mayoly, Allergan, Diasorin, Gebro Pharma, and Richen. Dr. Nyssen has received research funding from Mayoly and Allergan.