Prof Takashi KawaiVonoprazan, a first-in-class potassium-competitive acid blocker (P-CAB), produces a sustained gastric acid suppression effect that is both more profound and more rapid than that of proton pump inhibitors (PPIs), making it an essential component of first-line (1L) and second-line (2L) therapy for Helicobacter pylori eradication, according to Professor Takashi Kawai of Tokyo Medical University Hospital, Tokyo, Japan.
H. pylori is a leading cause of peptic ulcer, gastric adenocarcinoma, and gastric mucosa–associated lymphoid tissue lymphoma. Guidelines recommend H. pylori eradication whenever identified. [Gastroenterology 2022;163:608-619] Most antibiotics currently used to treat H. pylori infection require active bacterial replication, which is enhanced by raising intragastric pH to approximately 6–8. [Curr Gastroenterol Rep 2011;13:540-546] Furthermore, amoxicillin and, to a lesser degree, clarithromycin, are destabilized in acidic environment. [J Antimicrob Chemother 1997;39:5-12] Hence, for optimal results, the antibiotics need to be combined with agents that can effectively suppress gastric acid.
For decades, H. pylori treatment landscape has been dominated by PPI-based triple therapy comprising a PPI, clarithromycin, and amoxicillin or metronidazole. However, H. pylori eradication rates have been in decline due to antibiotic resistance. [Gastroenterology 2021;160:2181-2183.e1] A multicentre, randomized, open-label, noninferiority study (n=245) comparing esomeprazole vs lansoprazole in combination with amoxicillin and clarithromycin reported rates of primary eradication <80 percent for either agent. [World J Gastroenterol 2014;20:4362-4369]
“Outcome of PPI-based triple therapy is far from satisfactory,” commented Kawai. “Stronger acid control may improve rates of H. pylori eradication, and prioritizing the most effective initial regimen is critical to preventing subsequent treatment failure and resistance.”
Another randomized, double-blind, multicentre, parallel-group study (n=650) compared vonoprazan and lansoprazole as part of 1L triple therapy (with amoxicillin and clarithromycin) in H. pylori–positive patients with gastric or duodenal ulcer history. The 1L eradication rate was 92.6 percent with vonoprazan vs 75.9 percent with lansoprazole (p<0.0001). Furthermore, 50 patients who failed 1L therapy despite good compliance also received 2L vonoprazan-based triple therapy (with amoxicillin and metronidazole) as open-label treatment, which achieved an eradication rate of 98 percent. [Gut 2016;65:1439-1446]
In the same study, vonoprazan demonstrated a favourable safety profile that was similar to that of lansoprazole. During the 1L eradication phase, the overall incidence of treatment-emergent adverse events (TEAEs) was 34.0 percent with vonoprazan vs 41.1 percent with lansoprazole, while drug-related TEAEs were 20.4 vs 24.6 percent.
The greater efficacy of vonoprazan vs PPIs is due to P-CABs’ longer half-life, greater stability in acidic environment, faster onset of action, and almost complete inhibition of gastric acid secretion. Furthermore, P-CABs’ metabolism is unaffected by CYP2C19 polymorphisms, resulting in less individual variation in efficacy. In addition, vonoprazan can be taken once daily on an empty stomach or after a meal, which makes it convenient to use. [Eur J Clin Pharmacol 2025;81:1773-1786]
“In Japan, vonoprazan was registered in 2015 and has largely replaced PPI-based regimens in treatment of H. pylori infection,” shared Kawai. “A study based on a Japanese nationwide claims database, which included records from >480,000 patients, found that success rate of H. pylori eradication decreased between 2011 and 2014, eventually dropping to <80 percent, which was probably due to the rise of drug-resistant strains. However, the trend changed in early 2015, coinciding with vonoprazan’s launch, with success rate rising to >90 percent by March 2016.” [Digestion 101:441-449]