Additional considerations on vonoprazan triple therapy for Helicobacter pylori eradication: Implementation challenges and clinical perspectives

Abstract

The vonoprazan (VPZ) triple therapy regimen for Helicobacter pylori (H. pylori) eradication developed by Han et al employs a scientifically rigorous clinical trial design. This multicenter randomized controlled trial establishes a standardized treatment framework aimed at improving H. pylori eradication rates, focusing on simplifying treatment regimens, shortening therapy duration, and optimizing therapeutic outcomes. The core of clinical translation lies in improving drug accessibility, establishing multidimensional safety evaluation systems, and optimizing cost-effectiveness. Conducting regional adaptability studies and comprehensive safety assessments is crucial for enhancing VPZ regimen effectiveness in China’s diverse healthcare environments. This study provides important evidence-based support for optimizing H. pylori treatment strategies in China, though further validation of universal applicability for nationwide implementation remains necessary.

Key Words: Helicobacter pylori; Vonoprazan; Multicenter trial; Regional differences; Clinical implementation

Core Tip: Han et al’s multicenter trial demonstrates vonoprazan triple therapy’s superior efficacy over standard bismuth quadruple therapy for Helicobacter pylori eradication in China, successful nationwide implementation faces critical challenges. Key barriers include limited drug accessibility in primary healthcare settings, higher costs compared to traditional therapies, and significant regional variations in antibiotic resistance patterns across China’s diverse population. The study’s single-province design cannot fully represent national applicability. Addressing these implementation gaps through comprehensive health system research, cost-effectiveness analyses, and multi-regional validation studies is essential for translating these promising clinical findings into improved patient outcomes across China’s heterogeneous healthcare landscape.

TO THE EDITOR

Helicobacter pylori (H. pylori) is a microaerophilic, spiral-shaped gram-negative bacterium with bundled flagella at its terminal ends, primarily colonizing the gastric mucosa. H. pylori infection is the principal cause of chronic gastritis, gastric ulcers, duodenal ulcers, gastric cancer, and mucosa-associated lymphoid tissue lymphoma[1]. Although H. pylori infection rates have declined in recent years, the global infection rate remains approximately 43.9%[2], making eradication of H. pylori infection critically important. According to the white paper on the prevention and control of H. pylori infection in China, published on June 3, 2023, by the National Institute for Communicable Disease Control and Prevention at the Chinese Center for Disease Control and Prevention, the infection rate of H. pylori in China is also close to 50%, with infection rates among different populations ranging from 35.4%-66.4%. Current first-line treatment recommendations in China include 14-day bismuth quadruple therapy; however, the multiple drug regimen, frequent adverse reactions, and poor compliance make optimization of H. pylori treatment protocols essential. In this context, the research by Han et al[3] deserves particular attention.

Han et al[3] conducted a multicenter, prospective, open-label, randomized controlled trial involving 545 patients across 19 clinical trial centers in Shandong Province. The study utilized vonoprazan (VPZ), a novel potassium-competitive acid blocker, and designed a three-arm comparative trial including 14-day VPZ triple therapy, a shortened 10-day regimen, and standard bismuth quadruple therapy. As China’s first large-scale prospective trial directly comparing VPZ triple therapy with standard bismuth quadruple therapy, this study provides important evidence for optimizing H. pylori eradication strategies while exploring the feasibility of shortened treatment courses. The results were encouraging: VPZ triple therapy demonstrated significantly superior eradication rates compared to the control group in intention-to-treat analysis (88.0% vs 72.6%, P < 0.001), and the 10-day regimen also met non-inferiority criteria.

The authors objectively summarized the main limitations of their study, including short follow-up periods and lack of antibiotic susceptibility testing, while providing perspectives on future research directions. Inspired by their work, we would like to discuss several practical considerations affecting the clinical implementation of VPZ protocols based on their findings.

First, the depth of adverse event assessment requires enhancement. While the study showed no significant differences in overall adverse event rates among the three groups (29.6%-36.6%), detailed safety stratification analyses for different age groups, patients with comorbidities, and drug interactions were lacking. Considering that VPZ is primarily metabolized through CYP3A4 and has potential interactions with commonly used medications such as statins and sedatives[4], we recommend future studies comprehensively evaluate the clinical significance of these drug interactions, particularly safety profiles in pediatric, elderly, and polypharmacy patients.

Second, attention should be paid to drug accessibility and cost-effectiveness assessment. Although VPZ has been widely used for H. pylori eradication treatment in Japan[5], its clinical use in China is still in the early promotion phase. According to the National Healthcare Security Administration Service Platform, the number of VPZ products included in China’s National Reimbursement Drug List is significantly fewer than commonly used bismuth-containing agents and proton pump inhibitors in standard regimens. Consequently, VPZ has relatively limited accessibility in primary healthcare institutions, particularly at the county and township levels, which restricts its widespread application in China’s hierarchical medical system. Additionally, compared to traditional proton pump inhibitors, VPZ has higher drug costs, which may limit its widespread application in resource-limited regions.

Third, from a clinical practice translation perspective, promoting VPZ triple therapy faces challenges in physician training and patient education. Transitioning from complex quadruple therapy to relatively simplified triple therapy requires clinicians to reconceptualize and adapt their approach. Meanwhile, patients may have efficacy concerns due to regimen simplification, necessitating appropriate patient education and communication.

Fourth, implementation of VPZ therapy must address potential antimicrobial stewardship concerns and long-term safety monitoring. Although Han et al[3] have emphasized the importance of antimicrobial susceptibility testing and demonstrated that VPZ triple therapy maintains high efficacy and good tolerability even in regions with high clarithromycin resistance rates, widespread empirical use without susceptibility testing may still exert selective pressure for dual-resistant H. pylori strains. Therefore, it is crucial to integrate VPZ use with antimicrobial stewardship programs, rapid molecular diagnostic testing to guide personalized treatment, and ongoing post-marketing surveillance.

Finally, while this study involved 545 patients with substantial scale and reliable conclusions, China’s vast territory encompasses significant regional differences in H. pylori strain distribution, antibiotic resistance patterns, dietary habits, and genetic backgrounds[6-8], with empirical antibiotic selection varying across regions. Data from a single province cannot fully represent the national situation. Therefore, promoting VPZ nationwide requires clinical observational studies in other regions to validate the universal applicability of VPZ regimens across China.

CONCLUSION

In conclusion, the multicenter randomized controlled trial published by Han et al[3] provides important evidence-based medicine support for VPZ in H. pylori eradication among Chinese populations. However, addressing these implementation challenges through comprehensive health system research is crucial for translating these promising findings into improved patient outcomes across China’s diverse healthcare environments.