Vonoprazan contributes to Helicobacter pylori eradication

Last Updated: 2016-03-30

By Will Boggs MD

NEW YORK (Reuters Health) - The potassium-competitive acid blocker vonoprazan is as effective as lansoprazole as part of triple therapy for Helicobacter pylori eradication, researchers from Japan report.

"High eradication rates by vonoprazan-based triple therapy may reduce the need for additional therapeutic approaches, such as sequential, quadruple, and long-term therapy for H. pylori eradication, which are commonly used in the world," Dr. Masahiro Asaka from the University of Hokkaido, Japan, told Reuters Health by email.

Vonoprazan, in preclinical studies, produced more potent and sustained acid-inhibitory effects and greater increases in gastric pH compared with lansoprazole.

Dr. Asaka and colleagues at 46 sites in Japan compared H. pylori eradication rates with vonoprazan-based triple therapy (with amoxicillin and clarithromycin) versus lansoprazole-based triple therapy in a phase 3 noninferiority study of 650 H. pylori-positive patients in 2012-2013.

The eradication rate was 92.6% in the vonoprazan group and 75.9% in the lansoprazole group, which satisfied the predetermined noninferiority criteria and suggested a difference in favor of vonoprazan.

"Vonoprazan-based triple therapy showed a high eradication rate (82.0%) in those patients with clarithromycin (CLR)-resistant strains," Dr. Asaka said. "It is actually amazing, since commonly eradication rates in CLR-resistant persons are about 20-30%."

Among the first 50 patients who failed first-line therapy and received vonoprazan-based triple therapy, the eradication rate was 98.0%, according to the March 2 online report in Gut.

In post hoc analyses, vonoprazan eradication rates were significantly higher than lansoprazole eradication rates for patients younger than 65 years, men and women, CYP2C19 extensive metabolizers, those infected with amoxicillin-susceptible and -resistant strains, and those infected with CLR-resistant strains.

The rates of adverse events were similar in the two treatment groups.

"Vonoprazan should be used as a first-line therapy for H. pylori eradication in the world," Dr. Asaka concluded. "High eradication rates by vonoprazan-based first-line triple therapy will be able to reduce the need for second-line eradication therapy, and therefore reduce the use of unnecessary antibiotics. This may avoid further development of antibiotics resistance, and also may reduce safety issues."

Dr. David Y. Graham, from Baylor College of Medicine, Houston, Texas, who has published extensively about H. pylori, told Reuters Health by email, "Although the combination with vonoprazan was better, neither provided an acceptable cure rate. One goal of H. pylori therapy is to identify a therapy containing only one antibiotic that with an antisecretory agent would reliably cure H. pylori. Proton pump inhibitors (PPIs) have failed to reliably do that because they fail to maintain the intragastric pH near neutral for 24 hours even when given four times daily. Higher doses of vonoprazan may accomplish this goal."

"In Japan and most of the world resistance to clarithromycin has increased to the point where it should not be given as an empiric therapy (e.g., 30% in Japan)," Dr. Graham said. "Those with resistant infections in Japan achieved poor cure rates even with vonoprazan, and clarithromycin should no longer be included in treatment for H. pylori unless the infection has been proven to be susceptible to the antibiotic."

Dr. Yaron Niv, from Rabin Medical Center, Tel Aviv University, Israel recently reviewed the treatment of H. pylori with doxycycline (http://bit.ly/1qiXMxf). He told Reuters Health by email, "Vonoprazan may replace PPI, being more effective in acid suppression. It also may have some direct inhibitory effect on Helicobacter pylori proliferation or survival."

"More randomized controlled trials should be conducted, comparing acceptable eradication treatments, such as concomitant or sequential therapies, before we change our management of Helicobacter pylori infection," Dr. Niv said. "Research should also be conducted in other populations (in Europe and USA), with not such a high prevalence of amoxicillin resistance(21.9%-40.8%), and with lower CYP2C19 extensive metabolizers (83.3% to 86%)."

Takeda Pharmaceutical Company sponsored the trial, employed four of the six authors, and had consulting relationships with the other two authors.

SOURCE: http://bit.ly/1ROHCaW

Gut 2016.