The Superiority of Vonoprazan-based First-line Triple Therapy with Clarithromycin: A Prospective Multi-center Cohort Study on <i>Helicobacter pylori</i> Eradication

Abstract

Objective We evaluated the safety and efficacy of vonoprazan-based amoxicillin and clarithromycin 7-day triple therapy (VAC) in comparison to proton pump inhibitor (PPI)-based (PAC) as a first-line treatment and vonoprazan-based amoxicillin and metronidazole 7-day triple therapy (VAM) in comparison to PPI-based (PAM) as a second-line treatment for the eradication of Helicobacter pylori in Japan. Methods We performed a non-randomized, multi-center, parallel-group study to compare first-line VAC to PAC and second-line VAM to PAM. A pre-planned subgroup analysis on CAM resistance was also performed. Safety was evaluated with an adverse effects questionnaire (AEQ), which was completed by patients during therapy. Results The first-line eradication rates (ER) in the intention-to-treat (ITT) and per protocol (PP) analyses were 84.9% (95% CI: 81.9-87.6%, n=623) and 86.4% (83.5-89.1%, n=612), respectively, for VAC and 78.8% (75.3-82.0%, n=608) and 79.4% (76.0-82.6%, n=603), respectively, for PAC. The ER of VAC was higher than that of PAC in the ITT (p=0.0061) and PP analyses (p=0.0013). The ERs for VAC in patients with CAM-resistant and CAM-susceptible bacteria were 73.2% (59.7-84.2%, n=56) and 88.9% (83.4-93.1%, n=180), respectively. PAC was associated with higher AEQ scores for diarrhea, nausea, headache, and general malaise. In the second-line ITT and PP analyses VAM achieved ERs of 80.5% (74.6-85.6%, n=216) and 82.4% (76.6-87.3%, n=211), respectively, while PAM achieved ERs of 81.5% (74.2-87.4%, n=146) and 82.1% (74.8-87.9%, n=145), respectively. No significant differences were observed in the ITT (p=0.89) or PP (p=1.0) analyses. Conclusion The ER of first-line VAC was higher than that of PAC, but still <90%. No difference was observed between second-line VAM and PAM. Vonoprazan-based triple therapy was safe and well tolerated.

Smoking and Drinking Did Not Increase the Failure of Therapeutic Helicobacter pylori Eradication by Vonoprazan, Clarithromycin, and Amoxicillin

“…P-CAB inhibits H + , K + -ATPase-mediated gastric acid secretion, and vonoprazan suppresses gastric acid secretion more potently than PPIs [22][23][24]. There have been many studies indicating that H. pylori eradication with triple therapy including vonoprazan is more efficient compared with eradication using PPIs [25][26][27][28][29][30][31][32][33][34][35][36]. However, these studies did not clearly demonstrate that lifestyle-related factors, including smoking and drinking, had any influence on eradication rates following triple therapy incorporating vonoprazan.…”

Gastric Mucosal Atrophy Might Be Associated with the Efficacy of First-Line Therapy Using Vonoprazan for &lt;i&gt;Helicobacter pylori&lt;/i&gt;

“…Several studies have investigated the efficacy of first-line eradication of H. pylori with VPZ therapy, and successful eradication rates using VPZ were 62.3% -95.8% by ITT analysis and 81.7% -95.7% by PP analysis [13]- [27]. In our study of a large sample, the eradication rate for VPZ therapy was significantly higher than that with PPI therapy in H. pylori-positive patients.…”

“…however, it was not significantly more effective than PPI therapy [40] Sue et al [27] reported that CAM resistance had a significant impact on eradication failure of first-line VPZ therapy. First-line VPZ therapy could overcome CAM-resistant strains and increased the eradication rate [13] [15] [17].…”

“…Other studies also reported that H. pylori eradication rates for 7-day P-CAB-based triple therapies were more effective than those of PPI-based triple therapies; however, these were retrospective studies with small sample sizes [14]- [24]. Recently, meta-analyses [25] and prospective studies [26] [27] showed that the eradication rate of first-line VPZ therapy was higher than that with PPI therapy.…”

Efficacy and Tolerability of Second-Line Metronidazole Triple Therapy Using Vonoprazan for Helicobacter pylori Eradication in Japan—Comparative Study: Vonoprazan vs. Proton Pump Inhibitors

“…A double-blind phase 3 study of triple therapy with VPZ (VAC) for first-line H. pylori eradication showed a high success rate of 92.6% [13]. Recently, a retrospective study with a large sample size [14], a meta-analysis [15] and prospective studies [16] [17] showed that the eradication rate of first-line VPZ (VAC) therapy was higher than that with PPI (PAC) therapy. In Japan, MNZ triple therapy is decided as second-line therapy under the National Health Insurance System.…”