Table_1_Comparison of hepatotoxicity of tegoprazan, a novel potassium-competitive acid blocker, with proton pump inhibitors using real-world data: A nationwide cohort study.pdf

BackgroundProton pump inhibitors (PPIs) are acid suppressants that are frequently prescribed in many countries to reduce heartburn. A potassium-competitive acid blocker (P-CAB; tegoprazan) was launched relatively recently that also inhibits gastric acid secretion. This study aimed to compare the hepatotoxicity of the six existing PPIs with P-CAB.
MethodsThis retrospective cohort study was conducted between January 2019 and December 2020 and included data from the total population of 50 million inhabitants in Korea. Propensity score (PS) matching was performed using 10 variables, and the differences in hepatotoxicity between P-CAB and the six PPIs were compared in a similar distribution. The primary endpoint was hepatotoxicity which included toxic liver disease, hepatitis, hepatic failure, liver transplantation, and other liver diseases.
ResultsThe risk ratios (RR) of tegoprazan vs. the six PPIs (dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole) were all significant [RR: 0.70 (95% CI: 0.69–0.72), 0.81 (95% CI: 0.79–0.83), 0.61 (95% CI: 0.59–0.63), 1.17 (95% CI: 1.13–1.20), 0.61 (95% CI: 0.59–0.62), and 0.73 (95% CI: 0.71–0.75), respectively]. The risk ratio of tegoprazan vs. the six existing PPIs was 0.73 (95% CI: 0.72–0.75). The hazard ratios (HRs) of hepatotoxicity of the six PPIs to tegoprazan showed significantly higher values apart from omeprazole (HR: dexlansoprazole, 1.13; esomeprazole, 1.04; lansoprazole, 1.25; omeprazole, 0.77; pantoprazole, 1.26; rabeprazole, 1.15, respectively, and the six existing PPIs, 1.10).
ConclusionUsing a large-scale data cohort analysis consisting of 50 million Koreans, tegoprazan did not induce higher hepatotoxicity compared with the six conventional PPIs.

背景：质子泵抑制剂（Proton pump inhibitors, PPIs）是一类抑酸药物，在多国被广泛用于缓解胃灼热症状。近期获批上市的钾竞争性酸阻滞剂（potassium-competitive acid blocker, P-CAB；替戈拉生，tegoprazan）同样可抑制胃酸分泌。本研究旨在对比六种现有质子泵抑制剂与P-CAB的肝毒性风险。
方法：本研究为回顾性队列研究，纳入2019年1月至2020年12月韩国全境5000万常住人口的医疗数据。研究采用10项变量进行倾向得分（Propensity score, PS）匹配以均衡各组基线特征，进而对比P-CAB与六种PPIs之间的肝毒性差异。本研究的主要终点为肝毒性事件，涵盖中毒性肝病、肝炎、肝衰竭、肝移植及其他肝脏疾病。
结果：替戈拉生对比六种PPIs（右兰索拉唑、埃索美拉唑、兰索拉唑、奥美拉唑、泮托拉唑及雷贝拉唑）的风险比（risk ratios, RR）均具有统计学显著性[RR分别为0.70（95%CI：0.69~0.72）、0.81（95%CI：0.79~0.83）、0.61（95%CI：0.59~0.63）、1.17（95%CI：1.13~1.20）、0.61（95%CI：0.59~0.62）及0.73（95%CI：0.71~0.75）]。替戈拉生对比六种现有PPIs的整体风险比为0.73（95%CI：0.72~0.75）。六种PPIs相对于替戈拉生的肝毒性风险比（hazard ratios, HRs）除奥美拉唑外均显著升高[HR分别为：右兰索拉唑1.13、埃索美拉唑1.04、兰索拉唑1.25、奥美拉唑0.77、泮托拉唑1.26、雷贝拉唑1.15；六种PPIs整体HR为1.10]。
结论：基于涵盖5000万韩国人群的大规模队列数据分析，替戈拉生的肝毒性风险未高于六种传统质子泵抑制剂。