麻豆传媒

Vonoprazan (Voquezna) was noninferior to lansoprazole (Prevacid) for healing patients with erosive esophagitis, and was superior for maintaining healing, a randomized trial showed.

In a modified intention-to-treat analysis including over 1,000 patients, 92.9% of those who received vonoprazan experienced healing by week 8 compared with 84.6% taking lansoprazole (P<0.0001), which fell within the 10% margin of noninferiority, reported Loren Laine, MD, of the Yale School of Medicine in New Haven, Connecticut, and colleagues.

The potassium-competitive acid blocker was also noninferior to the proton pump inhibitor (PPI) for heartburn-free days (mean 66.8 vs 64.1) and superior for healing severe esophagitis -- defined by Los Angeles (LA) grade C or D -- at 2 weeks (70.2% vs 52.6%, P=0.0008), the authors noted in .

"Differences in favor of vonoprazan were greater in patients with LA grade C/D esophagitis than in those with LA grade A/B esophagitis," they wrote. "Our prespecified analyses indicated superiority for vonoprazan in patients with LA grade C/D esophagitis, while post hoc analyses did not establish superiority in those with LA grade A/B esophagitis."

During maintenance, vonoprazan showed noninferiority to lansoprazole at 24 weeks at both the 10-mg and 20-mg doses (79.2% and 80.7% vs 72%, respectively, P<0.0001 for both), and noninferiority was maintained in a sensitivity analysis.

Moreover, both doses of vonoprazan were superior for maintaining healing in severe esophagitis (74.7% and 77.2% vs 61.5%, respectively) and for all grades combined. Both doses also were noninferior to lansoprazole for heartburn-free days during maintenance.

Notably, similar findings for healing with vonoprazan versus lansoprazole were observed in the per-protocol analysis (94.7% vs 86.6%, P<0.0001 for noninferiority). Vonoprazan continued to be noninferior in maintenance of healing at 24 weeks for both the 10 mg (89.2%) and 20 mg (90.7%) doses versus lansoprazole (79.7%).

"The data for vonoprazan healing severe (grade C/D) erosive esophagitis is quite impressive," Scott Gabbard, MD, of the Cleveland Clinic in Ohio, told 麻豆传媒.

"If approved, vonoprazan would be a nice option for any patient with erosive esophagitis who is intolerant of PPIs," added Gabbard, who was not involved in the study. "It should be noted that vonoprazan did appear to raise serum gastrin levels more than lansoprazole, and the long-term effect of this drug-induced hypergastrinemia is unclear."

Gastroesophageal reflux disease (GERD) remains one of the most common gastrointestinal tract disorders, and can lead to erosive esophagitis. Guidelines have recommended the use of PPIs for erosive esophagitis, for which healing is relative to the "degree and duration of gastric acid inhibition," Laine's group noted.

PPIs have been the mainstay of treatment for erosive esophagitis, but come with restrictions on timing of administration, and some patients fail to achieve success or experience relapse over time.

Phathom Pharmaceuticals, the developer of vonoprazan, is for the treatment of erosive esophagitis; two vonoprazan-based dual and triple regimens were approved earlier this year for Helicobacter pylori in adults.

For this study, Laine and colleagues randomized 1,024 adults with endoscopy-confirmed erosive esophagitis 1:1 to vonoprazan 20 mg or lansoprazole 30 mg once a day for up to 8 weeks from November 2019 to November 2020 across 77 U.S. centers and 34 European centers.

For the maintenance phase, 878 patients who experienced healing were re-randomized 1:1:1 to receive 10 mg or 20 mg of vonoprazan or 15 mg of lansoprazole once daily for 24 weeks.

Mean patient age was 51-52, and 50-56% were women. Over one-third had grade C/D esophagitis.

The most common adverse events were diarrhea during the healing phase and COVID-19 during the maintenance phase. Two maintenance patients in the 20-mg vonoprazan group died from COVID-19.

Laine and colleagues acknowledged that their findings are mainly generalizable only to white patients, who made up the majority of their study (89-92%). Additionally, these results may not apply to those with only GERD-like symptoms (heartburn) or those with H. pylori.

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