Sue Soichiro, Kuwashima Hirofumi, Iwata Yuri, Oka Hiroyuki, Arima Isao, Fukuchi Takehide, Sanga Katsuyuki, Inokuchi Yasuhiro, Ishii Yuniba, Kanno Masatomo, Terada Masahiro, Amano Hitoshi, Naito Makoto, Iwase Shigeru, Okazaki Hiroshi, Komatsu Kazuto, Kokawa Atsushi, Kawana Ichiro, Morimoto Manabu, Saito Toshifumi, Kunishi Yosuke, Ikeda Akihiko, Takahashi Daisuke, Miwa Haruo, Sasaki Tomohiko, Tamura Toshihide, Kondo Masaaki, Shibata Wataru, Maeda Shin
Department of Gastroenterology, Yokohama City University Graduate school of Medicine, Japan.
Department of Gastroenterology, Yokohama Hodogaya Central Hospital, Japan.
Intern Med. 2017;56(11):1277-1285. doi: 10.2169/internalmedicine.56.7833. Epub 2017 Jun 1.
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.
目的 我们评估了在日本用于根除幽门螺杆菌的一线治疗中，基于沃克帕唑的阿莫西林和克拉霉素7天三联疗法（VAC）与基于质子泵抑制剂（PPI）的疗法（PAC）相比的安全性和有效性，以及二线治疗中基于沃克帕唑的阿莫西林和甲硝唑7天三联疗法（VAM）与基于PPI的疗法（PAM）相比的安全性和有效性。方法 我们进行了一项非随机、多中心、平行组研究，以比较一线的VAC与PAC以及二线的VAM与PAM。还对克拉霉素（CAM）耐药情况进行了预先计划的亚组分析。通过患者在治疗期间完成的不良反应问卷（AEQ）评估安全性。结果 在意向性分析（ITT）和符合方案分析（PP）中，VAC的一线根除率（ER）分别为84.9%（95%CI：81.9 - 87.6%，n = 623）和86.4%（83.5 - 89.1%，n = 612），而PAC的一线根除率分别为78.8%（75.3 - 82.0%，n = 608）和79.4%（76.0 - 82.6%，n = 603）。VAC的根除率在ITT分析（p = 0.0061）和PP分析（p = 0.0013）中均高于PAC。在CAM耐药菌和CAM敏感菌患者中，VAC的根除率分别为73.2%（59.7 - 84.2%，n = 56）和88.9%（83.4 - 93.1%，n = 180）。PAC与腹泻、恶心、头痛和全身不适的AEQ评分较高相关。在二线ITT和PP分析中，VAM的根除率分别为80.5%（74.6 - 85.6%，n = 216）和82.4%（76.6 - 87.3%，n = 211），而PAM的根除率分别为81.5%（74.2 - 87.4%，n = 146）和82.1%（74.8 - 87.9%，n = 145）。在ITT分析（p = 0.89）或PP分析（p = 1.0）中未观察到显著差异。结论 一线VAC的根除率高于PAC，但仍<90%。二线VAM和PAM之间未观察到差异。基于沃克帕唑的三联疗法安全且耐受性良好。
