Second‑line triple therapy in failures with vonoprazan‑based triple therapy for eradication of Helicobacter pylori

Abstract

Abstract. Gastric acid inhibition during treatment is important for the eradication of Helicobacter pylori (H. pylori) infection. A novel potassium-competitive acid blocker, vonoprazan (VPZ), has been demonstrated to achieve high eradication rates; however, the efficacy of second-line treatment in failures of VPZ-based triple therapy has not been well studied.The aim of the current study was to determine the efficacy of VPZ in a first-line regimen for H. pylori eradication, and the efficacy of a second-line regimen using metronidazole (MTZ) in failures with the first-line regimen. Of 580 subjects enrolled in the study, 524 patients completed first-line treatment (275 patients who received VPZ and 249 patients who received LPZ). First-line regimens consisted of a combination of clarithromycin (CAM) 200 or 400 mg twice a day, amoxicillin (AMPC) 750 mg twice a day, and either LPZ 30 mg or VPZ 20 mg twice a day, administered orally for 7 days. CAM and VPZ/LPZ were replaced with metronidazole (MTZ) 250 mg and rabeprazole 10 mg in the second-line regimens. The eradication of H. pylori was assessed by the H. pylori stool antigen test. The overall first-line eradication rate with VPZ was significantly higher than that with LPZ [91.0% (250/275) vs. 84.7% (211/249), respectively, P=0.030]. The dose of CAM (400 vs. 800 mg) did not affect the eradication rate in either the VPZ or LPZ regimens. The overall eradication rates of the second-line regimens with MTZ did not differ significantly between the VPZ-failure and LPZ-failure groups [87.0% (20/23) vs. 87.9% (29/33), respectively, P= 0.700]. Therefore, VPZ was significantly more effective than LPZ for first-line treatment. In patients with failure of first-line eradication therapy, successful results of second-line eradication therapy did not differ between the VPZ-and LPZ-failure groups. In conclusion, VPZ-based triple therapy should be recommended for eradication of H. pylori.

Efficacy of Vonoprazan for <i>Helicobacter pylori</i> Eradication

“…We searched for comparative studies that examined the rate of H. pylori eradication with vonoprazan-based triple therapies and PPI-based triple therapies using the key words "vonoprazan" and "pylori" in PubMed on November 1, 2018. Excluding the studies that did not show detailed data, 6 prospective studies (21-26) and 12 retrospective studies (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38) were assessed. The results of the studies are presented in Table 1.…”

“…Second, we must consider the various patterns of antibiotic resistance of H. pylori among regions. The Japanese studies described above investigated roughly the same eradication regimens: vonoprazan 20 mg + amoxicillin 750 mg + clarithromycin 200/400 mg or metronidazole 250 mg, twice (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). In Japan, the rate of clarithromycin resistance of H. pylori is more than 30%, whereas that of metronidazole resistance is less than 5% (55).…”

Role of Vonoprazan in Helicobacter pylori Eradication Therapy in Japan

“…In recent years, several studies have compared eradication rates between VPZ-containing and PPI-containing triple therapies across centers in Japan. As shown in Table 2, up until September 2018, 23 reports had investigated the efficacy of first-line VPZ-containing therapy (21 reports for VPZ/AMX/CLR and 2 reports for VPZ/MNZ/CLR) (Matsumoto et al, 2016; Murakami et al, 2016; Noda et al, 2016; Shichijo et al, 2016; Shinozaki et al, 2016, 2018; Suzuki et al, 2016; Tsujimae et al, 2016; Yamada et al, 2016; Kajihara et al, 2017; Katayama et al, 2017; Maruyama et al, 2017; Nishizawa et al, 2017; Ono et al, 2017; Sakurai et al, 2017; Sue et al, 2017a,b, 2018a; Sugimoto et al, 2017; Tanabe et al, 2017, 2018; Mori et al, 2018; Ozaki et al, 2018), and 19 reports had compared the efficacy between VPZ-containing therapy and PPI-containing therapy, including 3 randomized control trials (Murakami et al, 2016; Maruyama et al, 2017; Sue et al, 2018a) and 16 non-randomized retrospective cohort trials (Matsumoto et al, 2016; Noda et al, 2016; Shichijo et al, 2016; Shinozaki et al, 2016; Suzuki et al, 2016; Tsujimae et al, 2016; Yamada et al, 2016; Kajihara et al, 2017; Nishizawa et al, 2017; Ono et al, 2017; Sakurai et al, 2017; Sue et al, 2017a,b; Mori et al, 2018; Ozaki et al, 2018; Tanabe et al, 2018).…”

“…As shown in Table 2, first-line triple VPZ-containing therapies (VPZ/AMX/CLR) therefore show superior efficacy in Japanese individuals in terms of H. pylori eradication compared to PPI-containing therapies (Matsumoto et al, 2016; Murakami et al, 2016; Noda et al, 2016; Shichijo et al, 2016; Shinozaki et al, 2016, 2018; Suzuki et al, 2016; Tsujimae et al, 2016; Yamada et al, 2016; Kajihara et al, 2017; Katayama et al, 2017; Maruyama et al, 2017; Nishizawa et al, 2017; Ono et al, 2017; Sakurai et al, 2017; Sue et al, 2017a,b, 2018a; Sugimoto et al, 2017; Tanabe et al, 2017, 2018; Mori et al, 2018; Ozaki et al, 2018). According to a grading system established by Graham et al (2007) the 69.1–75.0% eradication rate of PPI-containing therapies constitutes an unacceptable grade (grade F).…”

Review: Treatment of Helicobacter pylori Infection 2019

“…67 Elsewhere in Japan, another study found vonoprazan triple therapy to be significantly more effective than standard therapy as first line (91% vs 85%) but not second line (87% vs 88%). 68 Two trials looked at the introduction of vonoprazan-based therapy as third line for patients who had failed two courses of PPI-based therapies. The first, a randomized controlled trial showed 76.8% eradication for vonoprazan, amoxicillin, and sitafloxacin, compared to 53% when PPI was used with those antibiotics.…”