Uemura Naomi, Kinoshita Yoshikazu, Haruma Ken, Kushima Ryoji, Yao Takashi, Akiyama Junichi, Aoyama Nobuo, Baba Yuji, Suzuki Chihiro, Ishiguro Kaori
Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Kohnodai Hospital, Ichikawa, Chiba, Japan.
General Internal Medicine, Hyogo Prefectural Harima-Himeji General Medical Center, Himeji, Hyogo, Japan.
Clin Gastroenterol Hepatol. 2025 Apr;23(5):748-757.e5. doi: 10.1016/j.cgh.2024.08.004. Epub 2024 Aug 27.
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.
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.
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.
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).
酸分泌抑制剂与高胃泌素血症相关，可导致胃黏膜改变。钾竞争性酸阻滞剂，如沃克，比质子泵抑制剂更有效，但缺乏长期安全性数据。
在这项IV期随机试验中，糜烂性食管炎（EE）患者接受诱导治疗（每日一次沃克20mg或兰索拉唑30mg；≤8周）。EE愈合的患者接受维持治疗（每日一次沃克10mg或兰索拉唑15mg）260周（2:1）。主要终点是恶性上皮细胞改变、壁细胞增生、小凹增生、肠嗜铬样（ECL）细胞增生和G细胞增生患者的比例。
总体而言，202/208例患者（沃克组，n = 139；兰索拉唑组，n = 69）实现EE愈合并接受维持治疗。未观察到恶性改变或胃神经内分泌肿瘤（NETs）；每组各有1例腺瘤。在第260周时，服用沃克的患者壁细胞增生（97.1%对86.5%）和小凹增生（14.7%对1.9%）明显多于服用兰索拉唑的患者；ECL细胞增生（4.9%对7.7%）和G细胞增生（85.3%对76.9%）患者的比例相似。沃克治疗组的血清胃泌素水平中位数高于兰索拉唑组（625 pg/mL对200 pg/mL）。两种治疗的不良事件发生率相当。
探索性VISION研究评估了沃克和兰索拉唑在日本EE愈合患者中5年的安全性。尽管沃克组的胃泌素浓度、壁细胞增生和小凹增生较高，但恶性上皮细胞改变和胃NETs的风险并未增加。（ClinicalTrials.gov，NCT02679508）
