Single-capsule bismuth quadruple therapy: Preferable at the moment,but what should be next?

Helicobacter pylori infection is associated with gastric cancer, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphomas and dyspepsia.^1,2 H. pylori eradication treatment has been shown to be effective against these diseases. Diverse treatment regimens for H. pylori eradication are being used across the world. This is because of the different profiles of resistant strains in each region and the different drugs available.³ For example, vonoprazan, which has a stronger acid suppression effect than proton pump inhibitors (PPI), can only be used in several Asian countries.⁴ Sitafloxacin, a quinolone with a strong bactericidal effect against H. pylori, can only be used in Japan and Thailand.⁴ On the other hand, regimens including bismuth have not been approved for use in Japan.

In this month’s issue of United European Gastroenterology Journal, Nyssen et al. reported large-scale real-world data on more than 2000 people, showing that three-in-one single-capsule bismuth quadruple therapy (BQT) performed well not only in rescue treatments but also in first-line therapy.⁵ Although BQT is already recommended as a first-line regimen in regions of high (>15%) dual clarithromycin and metronidazole resistance in the European guidelines Maastricht V/Florence Consensus Report, the level of evidence was low due to lack of large‐scale real‐world clinical data.⁶ From this point of view, their study provides strong evidence supporting the guidelines’ recommendation. The important data presented in their article are the analysis that treatment adherence is more important than the profile of resistant strains as a factor in successful eradication. Moreover, the adherence rate in their study was 96.7%, indicating that it is a well-accepted treatment. While there were a few serious adverse events, the overall rate of adverse events was 28.8%, which is not a low level compared to standard triple therapy. Safety is as important as efficacy especially in first-line treatment. Therefore, some disagree with the use of BQT as a first-line therapy.⁷

There is no doubt that it is better to use fewer drugs in a treatment regimen, not only to reduce side effects but also to suppress the rise of drug-resistant strains.⁸ Vonoprazan, a potassium-competitive acid blocker, is attracting attention as a drug that can be a game changer. Treatment with PPI replaced with vonoprazan in Japan exhibited superiority of vonoprazan over PPI, not only in standard triple therapy including amoxicillin and clarithromycin but also in triple therapy including amoxicillin and metronidazole, as well as triple therapy including amoxicillin and sitafloxacin.⁹ The most remarkable finding is that dual therapy with amoxicillin and vonoprazan has recently shown non-inferiority to triple therapy including amoxicillin, clarithromycin and vonoprazan.¹⁰ Reducing the variation of antibiotics is a desirable development in terms of suppressing the rise of resistant strains and reducing the occurrence of adverse events. In the future, when vonoprazan becomes available in Europe, it will be desirable for BQT to be preserved as a trump card for rescue therapy.