Phase III, randomised, double-blind, multicentre study to evaluate the efficacy and safety of vonoprazan compared with lansoprazole in Asian patients with erosive oesophagitis

Abstract

ObjectiveTo establish the non-inferior efficacy of vonoprazan versus lansoprazole in the treatment of Asian patients with erosive oesophagitis (EO).DesignIn this phase III, double-blind, multicentre study, patients with endoscopically confirmed EO were randomised 1:1 to receive vonoprazan 20 mg or lansoprazole 30 mg, once daily for up to 8 weeks. The primary endpoint was EO healing rate at 8 weeks. The secondary endpoints were EO healing rates at 2 and 4 weeks. Safety endpoints included treatment-emergent adverse events (TEAEs).ResultsIn the vonoprazan (n=238) and lansoprazole (n=230) arms, 8-week EO healing rates were 92.4% and 91.3%, respectively (difference 1.1% (95% CI –3.822% to 6.087%)). The respective 2-week EO healing rates were 75.0% and 67.8% (difference 7.2% (95% CI –1.054% to 15.371%)), and the respective 4-week EO healing rates were 85.3% and 83.5% (difference 1.8% (95% CI –4.763% to 8.395%)). In patients with baseline Los Angeles classification grade C/D, 2-week, 4-week and 8-week EO healing rates were higher with vonoprazan versus lansoprazole (2 weeks: 62.2% vs 51.5%, difference 10.6% (95% CI –5.708% to 27.002%); 4 weeks: 73.3% vs 67.2%, difference 6.2% (95% CI –8.884 to 21.223); and 8 weeks: 84.0% vs 80.6%, difference 3.4% (95% CI –9.187% to 15.993%)). Overall, EO healing rates appeared higher with vonoprazan versus lansoprazole. TEAE rates were 38.1% and 36.6% in the vonoprazan and lansoprazole group, respectively.ConclusionOur findings demonstrate the non-inferior efficacy of vonoprazan versus lansoprazole in terms of EO healing rate at 8 weeks in this population. Safety outcomes were similar in the two treatment arms.Trial registration numberNCT02388724.

Current knowledge on non-steroidal anti-inflammatory drug-induced small-bowel damage: a comprehensive review

“…Vonoprazan, which belongs to a class of acid-inhibitory agents called potassium-competitive acid blockers, was approved in Japan in February 2015, and its superiority or non-inferiority to PPIs for the treatment of acid-related diseases has been demonstrated [45][46][47]. Although vonoprazan suppresses gastric acid secretion by a different mechanism from PPIs, a recent animal study reported that both rabeprazole and vonoprazan aggravated NSAIDs-induced small intestinal injury in mice by reducing the population of Lactobacillus johnsonii in the small intestine [48].…”

Cytochrome P450-Based Drug-Drug Interactions of Vonoprazan In Vitro and In Vivo

“…As a potential alternative to proton-pump inhibitors (PPIs), vonoprazan has been verified to be superior to conventional PPIs or even more effective in distinct gastric acid-related clinical indications. A phase III multicenter study demonstrated that there was no significant difference between vonoprazan and lansoprazole in treating erosive esophagitis (Xiao et al, 2020). In terms of preventing the recurrence of low-dose or long-term aspirin-associated ulcers, vonoprazan has proven to be as effective as lansoprazole (Kawai et al, 2018).…”

Propensity score matching analysis: incidence and risk factors for “stardust” gastric mucosa, a novel gastric finding potentially induced by vonoprazan

“…Regarding safety, vonoprazan is well tolerated and has a similar incidence of treatment-emergent adverse events as lansoprazole (22.2%-38.1% vs. 22.3%-36.6%). 9,10 Vonoprazan users had higher serum gastrin levels than PPI users. 10,11 Hypergastrinaemia may be a potential risk for neuroendocrine tumours 12 ; nonetheless, no cases of neuroendocrine tumour caused by vonoprazan-associated hypergastrinaemia have been reported.…”