In the Journals

Novel acid blocker prevents GI ulcers in aspirin, NSAID users

Two new studies published in Gut showed that the novel acid blocker vonoprazan effectively prevented ulcer recurrence in aspirin and NSAID users, and thus has the potential to become a new treatment option.

Vonoprazan (Takeda) is a potassium-competitive acid blocker approved in Japan for the treatment of acid-related diseases, with several clinical advantages over PPIs, according to Takashi Kawai, MD, of the endoscopy center at Tokyo Medical University Hospital, and colleagues. “For example, vonoprazan does not require an acidic environment for activation and is acid stable, eliminating the need for an enteric-coated formulation,” they wrote. Additionally, it works faster, and “provides potent and long-lasting inhibition of gastric acid secretion, and its efficacy is therefore expected to be superior to that of PPIs.”

Vonoprazan in aspirin users

In their phase 3 double-blind non-inferiority study, Kawai and colleagues randomly assigned 621 patients on long-term low-dose aspirin with a history of peptic ulcers to receive either 10 mg or 20 mg vonoprazan or 15 mg of the conventional PPI lansoprazole once daily for 24 weeks. Afterward, they included 439 of these patients in a single-blind 2-year extension study.

At 24 weeks, peptic ulcers recurred in 0.5% of the 10-mg vonoprazan group, in 1.5% of the 20-mg vonoprazan-group and in 2.8% of the 15-mg lansoprazole group. A Farrington and Manning non-inferiority test with a margin of 8.7% showed both doses of vonoprazan were non-inferior to 15 mg lansoprazole (P < .001 for both).

Post hoc analyses of the extension study showed significantly lower peptic ulcer recurrence rates only in the 10-mg vonoprazan group vs. the lansoprazole group (P = .039). Kawai and colleagues therefore concluded that 10 mg vonoprazan should be the recommended clinical dose in this setting.

GI bleeding rates were higher with lansoprazole vs. both vonoprazan groups in both the 24-week study (2.9% vs. 0% for both doses), and in the extension study. Long-term administration of vonoprazan was well tolerated and showed a similar safety profile to lansoprazole.

“Vonoprazan therefore appears to be a useful alternative to lansoprazole for secondary prevention of [low-dose aspirin]-associated peptic ulcers at the recommended clinical daily dose of vonoprazan of 10 mg,” the investigators concluded.

Vonoprazan in NSAID users

In a related phase 3, double-blind, multicenter non-inferiority study, Yuji Mizokami, MD, of the endoscopic center at University of Tsukuba Hospital in Japan, and colleagues randomly assigned 642 patients on long-term NSAID therapy at risk for peptic ulcer recurrence to receive either 10 mg or 20 mg vonoprazan or 15 mg lansoprazole once daily for 24 weeks, followed by a 28-week extension study.

At 24 weeks, 3.3% of the 10-mg vonoprazan group, 3.4% of the 20-mg vonoprazan group and 5.5% of the lansoprazole group developed recurrent peptic ulcers. A Farrington and Manning test with an 8.3% margin confirmed the non-inferiority of both vonoprazan doses vs. lansoprazole (P < .001 for both). The drugs showed similar safety profiles, and again, the researchers concluded that 10 mg should be the recommended clinical dose of vonoprazan.

A promising alternative

In an accompanying editorial, Ali S. Taha, MD, of the department of medicine and gastroenterology at University Hospital Crosshouse and University of Glasgow School of Medicine in the U.K., said these findings mark a “new era in acid inhibition and gastroprotection.

“The results of the studies ... strengthen the promise of providing a new means of acid inhibition in addition to H2RAs and PPIs,” he wrote. “They also provide a different option to the healing and prevention of aspirin and NSAID-related ulcers.”

Given the advantages of vonoprazan and its class of drugs, including its rapid and longer-lasting acid inhibitory effects, Taha said it is likely that these novel agents could replace PPIs in the treatment of many acid-related disorders, although PPIs still play an important role in the management of GERD. However, he noted some limitations to the study findings and the future use of vonoprazan.

“These results do not necessarily imply that the doses of vonoprazan, tested in this study, are not inferior to the 30-mg standard dose of lansoprazole licensed for use outside Japan,” he wrote. “While vonoprazan has also been shown to be well tolerated, it cannot be claimed that its wider future use would not be linked to adverse events similar to those rightly or wrongly attributed to PPIs.” – by Adam Leitenberger

Reference:

Taha AS. Gut. 2017;doi:10.1136/gutjnl-2017-315252.

Disclosures: Both studies were funded by Takeda, and several study authors report employment and other financial relationships with Takeda. Taha reports no relevant financial disclosures.

Two new studies published in Gut showed that the novel acid blocker vonoprazan effectively prevented ulcer recurrence in aspirin and NSAID users, and thus has the potential to become a new treatment option.

Vonoprazan (Takeda) is a potassium-competitive acid blocker approved in Japan for the treatment of acid-related diseases, with several clinical advantages over PPIs, according to Takashi Kawai, MD, of the endoscopy center at Tokyo Medical University Hospital, and colleagues. “For example, vonoprazan does not require an acidic environment for activation and is acid stable, eliminating the need for an enteric-coated formulation,” they wrote. Additionally, it works faster, and “provides potent and long-lasting inhibition of gastric acid secretion, and its efficacy is therefore expected to be superior to that of PPIs.”

Vonoprazan in aspirin users

In their phase 3 double-blind non-inferiority study, Kawai and colleagues randomly assigned 621 patients on long-term low-dose aspirin with a history of peptic ulcers to receive either 10 mg or 20 mg vonoprazan or 15 mg of the conventional PPI lansoprazole once daily for 24 weeks. Afterward, they included 439 of these patients in a single-blind 2-year extension study.

At 24 weeks, peptic ulcers recurred in 0.5% of the 10-mg vonoprazan group, in 1.5% of the 20-mg vonoprazan-group and in 2.8% of the 15-mg lansoprazole group. A Farrington and Manning non-inferiority test with a margin of 8.7% showed both doses of vonoprazan were non-inferior to 15 mg lansoprazole (P < .001 for both).

Post hoc analyses of the extension study showed significantly lower peptic ulcer recurrence rates only in the 10-mg vonoprazan group vs. the lansoprazole group (P = .039). Kawai and colleagues therefore concluded that 10 mg vonoprazan should be the recommended clinical dose in this setting.

GI bleeding rates were higher with lansoprazole vs. both vonoprazan groups in both the 24-week study (2.9% vs. 0% for both doses), and in the extension study. Long-term administration of vonoprazan was well tolerated and showed a similar safety profile to lansoprazole.

“Vonoprazan therefore appears to be a useful alternative to lansoprazole for secondary prevention of [low-dose aspirin]-associated peptic ulcers at the recommended clinical daily dose of vonoprazan of 10 mg,” the investigators concluded.

Vonoprazan in NSAID users

In a related phase 3, double-blind, multicenter non-inferiority study, Yuji Mizokami, MD, of the endoscopic center at University of Tsukuba Hospital in Japan, and colleagues randomly assigned 642 patients on long-term NSAID therapy at risk for peptic ulcer recurrence to receive either 10 mg or 20 mg vonoprazan or 15 mg lansoprazole once daily for 24 weeks, followed by a 28-week extension study.

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At 24 weeks, 3.3% of the 10-mg vonoprazan group, 3.4% of the 20-mg vonoprazan group and 5.5% of the lansoprazole group developed recurrent peptic ulcers. A Farrington and Manning test with an 8.3% margin confirmed the non-inferiority of both vonoprazan doses vs. lansoprazole (P < .001 for both). The drugs showed similar safety profiles, and again, the researchers concluded that 10 mg should be the recommended clinical dose of vonoprazan.

A promising alternative

In an accompanying editorial, Ali S. Taha, MD, of the department of medicine and gastroenterology at University Hospital Crosshouse and University of Glasgow School of Medicine in the U.K., said these findings mark a “new era in acid inhibition and gastroprotection.

“The results of the studies ... strengthen the promise of providing a new means of acid inhibition in addition to H2RAs and PPIs,” he wrote. “They also provide a different option to the healing and prevention of aspirin and NSAID-related ulcers.”

Given the advantages of vonoprazan and its class of drugs, including its rapid and longer-lasting acid inhibitory effects, Taha said it is likely that these novel agents could replace PPIs in the treatment of many acid-related disorders, although PPIs still play an important role in the management of GERD. However, he noted some limitations to the study findings and the future use of vonoprazan.

“These results do not necessarily imply that the doses of vonoprazan, tested in this study, are not inferior to the 30-mg standard dose of lansoprazole licensed for use outside Japan,” he wrote. “While vonoprazan has also been shown to be well tolerated, it cannot be claimed that its wider future use would not be linked to adverse events similar to those rightly or wrongly attributed to PPIs.” – by Adam Leitenberger

Reference:

Taha AS. Gut. 2017;doi:10.1136/gutjnl-2017-315252.

Disclosures: Both studies were funded by Takeda, and several study authors report employment and other financial relationships with Takeda. Taha reports no relevant financial disclosures.