Vonoprazan as a Long-term Maintenance Treatment for Erosive Esophagitis: VISION, a 5-Year, Randomized, Open-label Study.

BACKGROUND & AIMS: Acid secretion inhibitors are associated with hypergastrinemia, which can lead to gastric mucosal changes. Potassium-competitive acid blockers, such as vonoprazan, are more potent than proton pump inhibitors, but long-term safety data are lacking.

METHODS

In this phase IV, randomized trial, patients with erosive esophagitis (EE) received induction therapy (once daily vonoprazan 20 mg or lansoprazole 30 mg; ≤8 weeks). Those with healed EE received maintenance therapy (once daily vonoprazan 10 mg or lansoprazole 15 mg) for 260 weeks (2:1). The primary endpoint was the proportion of patients with malignant epithelial cell alterations, parietal cell hyperplasia, foveolar hyperplasia, enterochromaffin-like (ECL) cell hyperplasia, and G-cell hyperplasia.

RESULTS

Overall, 202/208 patients (vonoprazan, n = 139; lansoprazole, n = 69) achieved healed EE and received maintenance therapy. No malignant alterations or gastric neuroendocrine tumors (NETs) were observed; there was 1 adenoma in each group. At week 260, significantly more patients taking vonoprazan vs lansoprazole had parietal cell hyperplasia (97.1% vs 86.5%) and foveolar hyperplasia (14.7% vs 1.9%); proportions of patients with ECL cell hyperplasia (4.9% vs 7.7%) and G-cell hyperplasia (85.3% vs 76.9%) were similar. Median serum gastrin levels were higher with vonoprazan treatment vs lansoprazole (625 pg/mL vs 200 pg/mL). Incidences of adverse events were comparable for both treatments.

CONCLUSIONS

The exploratory VISION study assessed the safety profile of vonoprazan and lansoprazole over 5 years in Japanese patients with healed EE. Although gastrin concentration, parietal cell hyperplasia, and foveolar hyperplasia were higher in the vonoprazan group, there was no increased risk of malignant epithelial cell alterations and gastric NETs. (ClinicalTrials.gov, NCT02679508).