Digestive Diseases and Sciences

, Volume 62, Issue 11, pp 2955–2957 | Cite as

Vonoprazan-Based Helicobacter pylori Eradication Therapy: Time to Get Kompetitive?

Editorial
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Approximately one-half of the world’s population is reported to be infected with Helicobacter pylori [1], a cause of numerous gastrointestinal diseases including gastric or duodenal ulcers, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer [2, 3]. Eradication of H. pylori is the first option for the treatment of low-grade gastric MALT lymphoma. Furthermore, H. pylori eradication reduces the recurrence of peptic ulcer [4]. A recent Cochrane review reported that the risk of gastric cancer may be reduced through H. pylori eradication, particularly in Asia [5].

Despite recent updates regarding the advantages of H. pylori eradication, the decline in the H. pylori eradication rate following treatment with conventional antibiotic regimens [proton pump inhibitor (PPI) + amoxicillin + clarithromycin, twice daily for 1–2 weeks] is of concern for gastroenterologists. To increase the eradication rate, the efficacy of several regimens has been compared in clinical trials [6]. In Korea, for example, >40 randomized controlled trials (RCTs) of first-line H. pylori eradication regimens have been completed [7]; in a network meta-analysis of H. pylori eradication in Korea, where both H. pylori infection and gastric cancer are highly prevalent, alternative regimens such as sequential, hybrid, and concomitant therapies (sequential therapy: PPI and amoxicillin, twice daily for the first 5 days (or 7 days), thereafter PPI, clarithromycin, and metronidazole (or tinidazole), twice daily for the last 5 days (or 7 days); hybrid therapy: PPI and amoxicillin, twice daily for the first 5 days (or 7 days), thereafter PPI, amoxicillin, clarithromycin, and metronidazole, twice daily for the next 5 days (or 7 days); concomitant therapy: PPI, amoxicillin, clarithromycin and metronidazole, twice daily for 5–14 days) reported higher eradication rates than did conventional triple therapy [7]. Since most PPI-based regimens, including alternative regimens, failed to achieve acceptable eradication rates [7], regimens incorporating the potent potassium-competitive antisecretory drug vonoprazan rather than PPIs have been developed in an effort to improve the eradication rate [7, 8, 9].

In this issue of Digestive Diseases and Sciences, Tanabe et al. [8] reported their “real-world” experience regarding vonoprazan-based H. pylori eradication therapy. In their study, the eradication rates of first-line and second-line vonoprazan-based triple therapy (first-line: 20 mg of vonoprazan, 750 mg of amoxicillin, and 200 mg (or 400 mg) of clarithromycin, twice daily for 1 week; second-line: 20 mg of vonoprazan, 750 mg of amoxicillin, 250 mg of metronidazole, twice daily for 1 week) in per-protocol (PP) analysis in populations untested for antibiotic sensitivity were 94.4 and 97.1%, respectively. The eradication rate for first-line vonoprazan-based triple therapy in their study was comparable to or even higher than that reported in a recent meta-analysis of vonoprazan-based triple therapy [89.2% (95% confidence interval, 86.1–91.7%) in PP analysis] [10]. These results support the high efficacy of vonoprazan-based triple therapy without prior antibiotic sensitivity testing, even in regions where the clarithromycin resistance rate is high, such as in Japan [9]. In the study by Tanabe et al. [8], however, the eradication rate in intention-to-treat (ITT) analysis was relatively low (82.7%), failing to achieve an acceptable grade in the report card system proposed by Graham et al. (≥85% in ITT analysis) [11]. This gap of eradication rate between ITT and PP analyses may be due to the retrospective design of the study. Despite the relatively low incidence of adverse events (2% skin eruption, 0.8% taste disorder, and other minor adverse events), >7% of the patients included in the ITT analysis were excluded in the PP analysis; most appeared to be patients who did not undergo a urea breath test, in contrast to patients who were dropped from the analysis due to adverse events. Had all patients undergone the urea breath test, the eradication rate in the ITT analysis would have been higher. In a previous RCT by Murakami et al. [9], the eradication rate of vonoprazan-based triple therapy in ITT analysis was 92.6%. Overall, vonoprazan-based triple therapy appears to be a good regimen with a high eradication rate and an acceptable adverse events rate.

Although promising, the relatively low eradication rate for clarithromycin-resistant strains may be of concern regarding vonoprazan-based triple regimen. In the meta-analysis by Jung et al. [10], the eradication rate of vonoprazan-based triple therapy determined by ITT analysis was 97.9 (excellent grade) and 81.2% (poor grade) for clarithromycin-sensitive and clarithromycin-resistant strains, respectively. Although vonoprazan-based triple therapy may be a good choice for H. pylori eradication in countries or hospitals where antibiotic susceptibility testing is not yet available, the regimen may not be optimal for H. pylori eradication if the strains have demonstrated resistance to clarithromycin.

Vonoprazan-based regimens other than the standard triple regimen (with amoxicillin and clarithromycin) may help improve the eradication rate in patients with clarithromycin-resistant H. pylori infection. The results of the study by Tanabe et al. [8] reported the beneficial effect of a vonoprazan-based second-line regimen that consisted of vonoprazan, amoxicillin, and metronidazole. The eradication rate of the second-line regimen was 90.4 and 97.1% in the ITT and PP analyses, respectively. These results imply that vonoprazan may be useful in regimens other than the standard triple therapy. Previous meta-analyses showed that PPI-based alternative regimens including sequential, hybrid, and concomitant therapies were superior in terms of eradication rate compared with the PPI-based triple therapy [6, 7]. If vonoprazan is used in those alternative regimens, the eradication rate may be superior to that of vonoprazan-based triple therapy, even in patients with clarithromycin-resistant H. pylori infection.

To date, vonoprazan has been approved only in Japan. Moreover, only triple therapy is covered by the Japanese National Health Insurance System. Therefore, all studies of vonoprazan in first-line H. pylori eradication therapy thus far have been conducted with the triple regimen (either PPI or vonoprazan, amoxicillin, and clarithromycin) in Japan. More s studies on vonoprazan-based alternative regimens including sequential, hybrid, and concomitant therapy might provide a better understanding of the efficacy of vonoprazan-based eradication therapy.

Vonoprazan-based regimens other than the standard triple regimen (with amoxicillin and clarithromycin) may help increase the eradication rate in patients with clarithromycin-resistant H. pylori infection. The results of the study by Tanabe et al. [8] showed the beneficial effect of the vonoprazan-based second-line regimen that consisted of vonoprazan, amoxicillin, and metronidazole. The eradication rate of the second-line regimen was 90.4 and 97.1% in the ITT and PP analyses, respectively. These results imply that vonoprazan may be useful in regimens other than the standard triple therapy. Previous meta-analyses showed that PPI-based alternative regimens including sequential, hybrid, and concomitant therapies were superior in terms of eradication rate compared with the PPI-based triple therapy [6, 7]. If vonoprazan is used in those alternative regimens, the eradication rate may be increased over that of vonoprazan-based triple therapy, even in patients with clarithromycin-resistant H. pylori infection.

To date, vonoprazan has been approved only in Japan. Moreover, only triple therapy is covered by the Japanese National Health Insurance System. Therefore, all studies on vonoprazan in first-line H. pylori eradication therapy thus far have been conducted with the triple regimen (either PPI or vonoprazan, amoxicillin, and clarithromycin) in Japan. More subsequent studies on vonoprazan-based alternative regimens including sequential, hybrid, and concomitant therapy might provide a better understanding of the efficacy of vonoprazan-based eradication therapy.

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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Division of Gastroenterology, Department of Internal Medicine, Severance HospitalYonsei University College of MedicineSeoulRepublic of Korea
  2. 2.Department of Internal Medicine, Hanyang University Guri HospitalHanyang University College of MedicineGuriRepublic of Korea

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