Is Tegoprazan-Based Triple Therapy Effective in Regions with High Rates of Clarithromycin Resistance?

Triple therapy (consisting of a proton pump inhibitor [PPI], clarithromycin, and amoxicillin) is the standard first-line regimen for eradicating Helicobacter pylori infection. However, standard triple therapy has an unsatisfactory eradication rate, largely as a result of the increasing rate of antibiotic resistance. In response to the declining effectiveness of the standard triple therapy, treatments with various drug combinations for different durations have been introduced to improve the H. pylori eradication rate. According to the 2020 guidelines of Korea, 7-day triple therapy is the recommended first-line regimen in cases negative for clarithromycin resistance, whereas 14-day triple therapy is recommended in cases in which clarithromycin resistance testing was not performed. A potassium-competitive acid blocker (P-CAB)-based triple therapy has been suggested as an alternative to the standard triple therapy. P-CAB offers stronger and longerlasting gastric-acid suppression compared to other PPIs. Stronger acid suppression is linked to successful eradication of H. pylori. Based on this, we hypothesized that PCAB-based triple therapy would be superior to the standard treatment. Vonoprazan, a novel P-CAB approved in Japan, in combination with a triple-therapy regimen, reportedly achieves a higher eradication rate than PPI-based triple therapy. The Japanese guidelines now recommend vonoprazan-based triple therapy as the first-line regimen. Tegoprazan, another P-CAB, has been introduced in Korea for the treatment of H. pylori infection. In this issue of Gut and Liver, Jung et al. report the first results of 14-day tegoprazan-based triple therapy compared to PPIbased triple therapy. They compared tegoprazanand rabeprazole-based triple therapies in subjects diagnosed with H. pylori infection. The main finding of their retrospective study was that tegoprazan-based triple therapy showed a similar eradication rate and incidence of adverse events to rabeprazole-based triple therapy. The eradication rate of tegoprazan-based triple therapy was not significantly improved compared to rabeprazole-based triple therapy according to an intention-to-treat (ITT) analysis (76.7% vs 75.4%, p>0.999). In a per-protocol (PP) analysis, there was no significant difference in the eradication, adherence, and adverse-event rates between the tegoprazan and rabeprazole groups (p>0.999, p=0.443, and p=0.604, respectively). To be suitable for the first-line treatment of H. pylori, a regimen should demonstrate an eradication rate of >85% in an ITT analysis and >90% in a PP analysis. P-CABbased triple therapy was expected to achieve a higher eradication rate than PPI-based therapy because of its greater potency and longer-lasting antacid effect. Vonoprazanbased triple therapy is superior to PPI-based triple therapy as a first-line regimen, particularly against clarithromycinresistant strains, although most of the supporting studies were performed in Japan. Murakami et al. noted a significantly higher eradication rate with vonoprazan-based triple therapy (82%) compared to lansoprazole-based triple therapy (40%) in patients with clarithromycin-resistant H. pylori (p<0.0001). In the work of this study, tegoprazan-based triple therapy did not achieve the target range in the ITT (76.7%) or PP (83.4%) analysis and did not show superior efficacy to PPI-based triple therapy. Choi et al. reported that tegoprazan-based triple therapy for 7 days did not have a superior