The Superiority of Vonoprazan-based First-line Triple Therapy with Clarithromycin: A Prospective Multi-center Cohort Study on Helicobacter pylori Eradication

Soichiro Sue, Hirofumi Kuwashima, Yuri Iwata, Hiroyuki Oka, Isao Arima, Takehide Fukuchi, Katsuyuki Sanga, Yasuhiro Inokuchi, Yuniba Ishii, Masatomo Kanno, Masahiro Terada, Hitoshi Amano, Makoto Naito, Shigeru Iwase, Hiroshi Okazaki, Kazuto Komatsu, Atsushi Kokawa, Ichiro Kawana, Manabu Morimoto, Toshifumi Saito, Yosuke Kunishi, Akihiko Ikeda, Daisuke Takahashi, Haruo Miwa, Tomohiko Sasaki, Toshihide Tamura, Masaaki Kondo, Wataru Shibata, Shin Maeda, Soichiro Sue, Hirofumi Kuwashima, Yuri Iwata, Hiroyuki Oka, Isao Arima, Takehide Fukuchi, Katsuyuki Sanga, Yasuhiro Inokuchi, Yuniba Ishii, Masatomo Kanno, Masahiro Terada, Hitoshi Amano, Makoto Naito, Shigeru Iwase, Hiroshi Okazaki, Kazuto Komatsu, Atsushi Kokawa, Ichiro Kawana, Manabu Morimoto, Toshifumi Saito, Yosuke Kunishi, Akihiko Ikeda, Daisuke Takahashi, Haruo Miwa, Tomohiko Sasaki, Toshihide Tamura, Masaaki Kondo, Wataru Shibata, Shin Maeda

Abstract

Objective We evaluated the safety and efficacy of vonoprazan-based amoxicillin and clarithromycin 7-day triple therapy (VAC) in comparison to proton pump inhibitor (PPI)-based (PAC) as a first-line treatment and vonoprazan-based amoxicillin and metronidazole 7-day triple therapy (VAM) in comparison to PPI-based (PAM) as a second-line treatment for the eradication of Helicobacter pylori in Japan. Methods We performed a non-randomized, multi-center, parallel-group study to compare first-line VAC to PAC and second-line VAM to PAM. A pre-planned subgroup analysis on CAM resistance was also performed. Safety was evaluated with an adverse effects questionnaire (AEQ), which was completed by patients during therapy. Results The first-line eradication rates (ER) in the intention-to-treat (ITT) and per protocol (PP) analyses were 84.9% (95% CI: 81.9-87.6%, n=623) and 86.4% (83.5-89.1%, n=612), respectively, for VAC and 78.8% (75.3-82.0%, n=608) and 79.4% (76.0-82.6%, n=603), respectively, for PAC. The ER of VAC was higher than that of PAC in the ITT (p=0.0061) and PP analyses (p=0.0013). The ERs for VAC in patients with CAM-resistant and CAM-susceptible bacteria were 73.2% (59.7-84.2%, n=56) and 88.9% (83.4-93.1%, n=180), respectively. PAC was associated with higher AEQ scores for diarrhea, nausea, headache, and general malaise. In the second-line ITT and PP analyses VAM achieved ERs of 80.5% (74.6-85.6%, n=216) and 82.4% (76.6-87.3%, n=211), respectively, while PAM achieved ERs of 81.5% (74.2-87.4%, n=146) and 82.1% (74.8-87.9%, n=145), respectively. No significant differences were observed in the ITT (p=0.89) or PP (p=1.0) analyses. Conclusion The ER of first-line VAC was higher than that of PAC, but still <90%. No difference was observed between second-line VAM and PAM. Vonoprazan-based triple therapy was safe and well tolerated.

Keywords: 7-day triple therapy; Helicobacter pylori; eradication; vonoprazan.

Figures

Figure 1.
Figure 1.
Patient selection flow. UMIN, A registry of the International Committee of Medical Journal Editors (ICMJE). After the approval of vonoprazan (2015.2-2016.2), 1,231 first-line and 362 second-line eradication cases were analyzed in this study.
Figure 2.
Figure 2.
The first-line Helicobacter pylori eradication rates. CAM: clarithromycin, MIC: minimum inhibitory concentration, VAC: 1-week vonoprazan/AMPC/CAM eradication therapy, PAC: PPI (LPZ, RPZ, OPZ, or 1-week ESO)/AMPC/CAM eradication therapy, [ ]: 95% CI, ITT: intention-to-treat analysis, PP: per-protocol analysis
Figure 3.
Figure 3.
The relationship between susceptibility to CAM and the ER (VAC). VAC: 1-week vonoprazan/AMPC/CAM eradication therapy, MIC: minimum inhibitory concentration
Figure 4.
Figure 4.
The non-superiority of VAM versus PAM for first-line eradication. VAM: 1-week vonoprazan/AMPC/MNZ eradication therapy, PAM: 1-week PPI (LPZ, RPZ, OPZ, or ESO)/AMPC/MNZ eradication therapy, [ ]: 95% CI, ITT: intention-to-treat analysis, PP: per-protocol analysis

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Source: PubMed

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