Vonoprazan-based triple therapy knocks out resistant H. pylori infection

Vonoprazan-based triple therapy demonstrates potent activity and is well tolerated in the first-line treatment of patients with Helicobacter pylori, leading to high eradication of infection, including strains resistant to clarithromycin, as shown in a study from Japan.

A 7-day triple therapy regimen (VAC) consisting of vonoprazan (20 mg), amoxicillin (750 mg), and clarithromycin (200 mg) twice daily yielded overall eradication rates of 90.8 percent and 81.5 percent in per-protocol (PP) and intention-to-treat (ITT) analyses, respectively. [J Gastroenterol 2020;55:1054-1061]

More importantly, VAC helped overcome clarithromycin resistance, the investigators said.

Successful eradication remained high, regardless of clarithromycin susceptibility. The corresponding rates were 91.6 percent in sensitive strains and 89.4 percent in resistant strains in the PP analysis, and 80.0 percent and 84.0 percent, respectively, in the ITT analysis.

Age emerged as the sole predictor of eradication failure with VAC (odds ratio, 1.07, 95 percent confidence interval, 1.00–1.16; p=0.046). The overall incidence of adverse events was low (8.4 percent), which included diarrhoea (n=4), heartburn (n=5), rash (n=1), and dysgeusia (n=1). None of the patients required treatment discontinuation.

The study included 146 Japanese patients (median age, 63 years; 60 percent female), among whom 50 had clarithromycin resistance. In total, 131 patients underwent ¹³C-urea breath testing for the evaluation of eradication.

“Vonoprazan-based regimens have been widely utilized in Japan for H. pylori eradication since the demonstration of their effectiveness in phase III trials,” the investigators said. [Gut 2016;65:1439-1446]

In one study, first-line eradication with vonoprazan was superior to that with esomeprazole (86.3 percent vs 79.9 percent; p=0.019). This held true in other comparative studies, with eradication rates ranging 84–87 percent on vonoprazan as compared with 57–78 percent on proton pump inhibitors. [Digestion 2016;94:240-246; World J Gastroenterol 2017;23:668-675; J Dig Dis 2016;17:670-675; Intern Med 2017;56:1277-1285]

There are three possible explanations for the high eradication rates observed using vonoprazan, according to the investigators.

“First, when amoxicillin is used in combination with vonoprazan, the concentration of the former in the gastric mucosa increases due to the inhibition of gastric acid by [the latter]. Second, after the gastric pH rises, H. pylori shifts into the proliferation phase, and cell wall synthesis is accelerated. Since this is the target for amoxicillin, its antibacterial efficacy increases,” they pointed out. [Digestion 2020;101:743-751; Curr Gastroenterol Rep 2011;13:540-546]

“Third, amoxicillin is stable for longer periods at a higher intragastric pH. Therefore, potent suppression of the gastric acid by vonoprazan may provide a suitable environment for improved potency of the antimicrobial drug,” they continued. [Antimicrob Agents Chemother 1996;40:1327-1328]

Taken together, the evidence suggests that VAC could be valuable first-line treatment regimen for H. pylori infection, the investigators stated.

However, the prevalence of amoxicillin-resistant bacteria was not evaluated in the study, they acknowledged. Furthermore, vonoprazan is only available in selected parts of Asia, including Japan, so the results of the current study may not be generalized to other countries.

“Further studies will be needed to elucidate whether an optimized regimen of VAC could replace the current [regimens] in consideration of less impact on future antimicrobial resistance,” the investigators said.