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

Abstract EN

We thank Dr.

Kashani and Dr.

Abadi [1] for their interest in our article [2].

In Japan, seven-day vonoprazan-containing triple therapy with clarithromycin and amoxicillin or vonoprazan-containing triple therapy with metronidazole and amoxicillin are approved regimens [3], but vonoprazan-containing triple therapy with clarithromycin and metronidazole is not approved and is used only in clinical trials which was approved by the ethics committee.

Thus, people who cannot be given the standard triple therapy due to being allergic to penicillin are the subjects of this study.

In addition, these patients cannot be covered by their medical insurance system for Helicobacter pylori eradication and related examinations, so it is difficult to add antibiotic susceptibility testing after the diagnosis of H.

pylori infection for cost and ethical reason (this study was not designed to choose regimen by antibiotic resistance result).

About the sample size, as we have also written the reason is the rate of patients allergic to penicillin, which makes it difficult to recruit many patients for this type of study.

These are the explanations overall.

We also answer each question: (i)Generalization of the finding: We think the efficacy of this regimen is influenced by metronidazole resistance rates.

In Japan, the metronidazole resistance rate is not high, and it is reported that metronidazole-containing triple therapy as a first-line therapy showed high eradication rate (ER) [4].

It is an important point that the vonoprazan, clarithromycin, and metronidazole regimen demonstrated excellent ER in areas with a high rate of clarithromycin resistance in two studies [2, 5], but these were performed in a country with a low rate of metronidazole resistance compared to other countries.

We hope this regimen will be useful in countries with high clarithromycin but low metronidazole resistance rates as eradication regimen for those allergic to penicillin instead of PPI-based triple therapy with clarithromycin and metronidazole.

(ii)Factors affecting the success of treatment: In all cases, patients did not drink alcohol during therapy, because drinking alcohol is not allowed with metronidazole under Japanese pharmaceutical rules.

We did not report smoking status, but one of the twenty patients on the vonoprazan-based regimen was a smoker.

The physician instructed them to stop smoking during therapy in this case based on past research [6].

We agree that stopping smoking during therapy is desirable.

(iii)We reported the local (Kanagawa prefecture) clarithromycin resistance rate as 23.7% (95% CI: 18.5–29.7%, n=236) in a previous article [3] and 40% in the Yokohama City University hospital where the study was performed [2].

We agree that a prospective study with clarithromycin and metronidazole resistance information is important, but it may be ethically difficult to use clarithromycin or metronidazole for drug-resistant H.

pylori.

In Japan, we have continued to use the VCM regimen for penicillin-allergic patients without testing susceptibility and continued to have a 100% successful rate without any severe adverse events.

(iv)We agree that 95% CI of 86.1–100% result needs further confirmation at a large scale.

But it is difficult to perform a large-scale study for patients allergic to penicillin.