Comment on “First-Line Helicobacter pylori Eradication with Vonoprazan, Clarithromycin, and Metronidazole in Patients Allergic to Penicillin”

Aim. To assess the efficacy of 7-day first-line Helicobacter pylori eradication with vonoprazan (VPZ), clarithromycin (CAM), and metronidazole (MNZ) in patients with penicillin allergy. Methods. Patients with penicillin allergy, diagnosed with Helicobacter pylori infection and did not have history of Helicobacter pylori eradication, were eligible for the study. Twenty patients were prospectively treated with 20 mg VPZ twice daily, 200 or 400 mg CAM twice daily, and 250 mg MNZ twice daily for 7 days. We also collected the data from 30 patients retrospectively treated with proton pump inhibitor (PPI), CAM, and MNZ. Safety was evaluated in patients completing an adverse effect questionnaire. Results. Both the intention-to-treat and per-protocol effectiveness of VPZ-based eradication were 100% (95% CI: 86.1–100%; ). The eradication rates of PPI-based regimen were 83.3% (95% CI: 65.3–94.4%) in the ITT and 82.7% (95% CI: 64.2–94.2%) in the PP analyses. Abdominal fullness was more frequent in VCM compared to PCM. However, all patients with VCM regimen had taken 100% of their course of medication. Conclusion. Triple therapy with VPZ, CAM, and MNZ is well tolerated and effective for eradicating Helicobacter pylori in patients allergic to penicillin. This study was registered in the UMIN Clinical Trials Registry as UMIN000016335 .


Generalization of the Finding
The main limitation of this survey is the lack of blinding of the study design. This problem directly reduces the ability of generalization for Japanese patients. As an internal control, they should have used a crossover modification in their design for subjects. This item is highly suggested for similar studies in the future. On the other hand, vonoprazan application is restricted to Japan and there is no clue what would happen if it is prescribed by American, Iranian, or Indian gastroenterologists for H. pylori-infected patients! This is the main challenge in treating subjects worldwide.

Factors Affecting the Success of Treatment
Although both the intention-to-treat and per-protocol effectiveness of VPZ-based eradication were found to be 100% (95% CI: 86.1-100%) in this study, the factors affecting the success rate of H. pylori therapy were not checked. For example, the smoking situation and alcohol-drinking habits could be valuable candidates to investigate. The consistency of the current finding (100% eradication rate for therapy) can be reevaluated in the condition of those defined queries in Japanese subjects.

Clarithromycin and Metronidazole Resistance
It has been documented that clarithromycin-based triple therapy (1-2 weeks) is a standard for Asian countries [3], but we need to first check local levels of antibiotic resistance. In this study, there is no clue about those necessary data. Broadly defined, anti-H. pylori therapy using clarithromycin is bound to be defeated in the case of high clarithromycin resistance (>20%). In Japan, clarithromycin resistance has quickly increased, and the current resistance rate is 27.7% [4,5]. The importance of the current point is higher if we address that the authors aimed to recommend this regimen as the first-line therapy against H. pylori infection [1]. Similar to clarithromycin, the story is even worse for metronidazole. The mean range of resistance to metronidazole in Asian countries is more than 55%, a fact which reduces the chance of success in regimens using this futile antibiotic against H. pylori [6]. Sue et al. did not report data on susceptibility profile for their patients. In fact, clinicians need to have this pattern to reduce antibiotic resistance in patients.

Population Size
As a prospective study, it is not far from the mind to expect a better sample size at least for the vonoprazan-receiving group (n = 20). In Table 1, it is clear that most of the studies in the case of vonoprazan included more subjects than Sue et al. [1]. Additionally, this study was performed at a single medical center which again limits the chance of generalization of the results. Therefore, the statistical power of the study is under question.

Ethical Considerations
Although the authors addressed that this study is not a randomized clinical trial, there are some ethical considerations which are already neglected. The authors performed endoscopy surgery for diagnostic purposes using the antral biopsies in bacterial culture. Interestingly, IgG serum analysis was performed which is enough. Now, the query is about the accuracy of ethical consideration. It is definitely unacceptable to use an invasive method in H. pylori diagnosis while a noninvasive method is conducted at the same time. Taking together, vonoprazan-based triple therapy showed superiority in treating the H. pylori infection in comparison with PPI-based therapy. Meanwhile, we should not forget that an optimal anti-H. pylori therapy is what eradicates the bacterium in all subjects with minimal side effects, cost, and ethical considerations.