Howden Colin W, Scarpignato Carmelo, Leifke Eckhard, Mulford Darcy J, Lahu Gezim, Facius Axel, Yuan Yuhong, Hunt Richard
University of Tennessee College of Medicine, Memphis, Tennessee, USA.
Department of Health Sciences, United Campus of Malta, Msida, Malta.
CPT Pharmacometrics Syst Pharmacol. 2025 Jan;14(1):28-41. doi: 10.1002/psp4.13235. Epub 2024 Sep 19.
Effective suppression of gastric acid secretion promotes healing of erosive esophagitis. Treatment guidelines recommend proton pump inhibitors (PPIs) and histamine H-receptor antagonists (HRAs). Emerging evidence also supports potassium-competitive acid blockers (P-CABs). The aim was to construct a mathematical model to examine the relationship between pH holding time ratios (HTRs) and erosive esophagitis healing rates with HRAs, PPIs and P-CABs. By literature search, we identified studies of HRAs, PPIs or P-CABs that reported mean pH >4 HTRs at steady state (days 5-8) and erosive esophagitis healing rates after 4 and/or 8 weeks. We aggregated treatments by drug class and developed a non-linear, mixed-effects model to explore the relationship between pH >4 HTRs and healing rates. The pH dataset included 82 studies (4297 participants; 201 dosage arms); healing rate data came from 103 studies (43,417 patients; 196 treatment arms). P-CABs achieved the longest periods with intragastric pH >4, and the highest healing rates after 4 and 8 weeks. The predicted probabilities of achieving ≥90% healing rates at 8 weeks were 74.1% for P-CABs, 17.3% for PPIs and 0% for HRAs. P-CABs provide the longest duration with intragastric pH >4 and, accordingly, the highest healing rates of erosive esophagitis.
有效抑制胃酸分泌可促进糜烂性食管炎的愈合。治疗指南推荐使用质子泵抑制剂（PPI）和组胺H受体拮抗剂（HRA）。新出现的证据也支持钾竞争性酸阻滞剂（P-CAB）。本研究旨在构建一个数学模型，以研究使用HRA、PPI和P-CAB时的pH维持时间比（HTR）与糜烂性食管炎愈合率之间的关系。通过文献检索，我们确定了有关HRA、PPI或P-CAB的研究，这些研究报告了稳态（第5 - 8天）时平均pH >4的HTR以及4周和/或8周后的糜烂性食管炎愈合率。我们按药物类别汇总治疗方法，并开发了一个非线性混合效应模型，以探索pH >4的HTR与愈合率之间的关系。pH数据集包括82项研究（4297名参与者；201个剂量组）；愈合率数据来自103项研究（43417名患者；196个治疗组）。P-CAB使胃内pH >4的时间最长，在4周和8周后的愈合率最高。在8周时达到≥90%愈合率的预测概率，P-CAB为74.1%，PPI为17.3%，HRA为0%。P-CAB使胃内pH >4的持续时间最长，因此糜烂性食管炎的愈合率最高。
