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瑞美替罗（Resmetirom）治疗代谢相关脂肪性肝炎的临床试验进展
DOI: 10.12449/JCH250122
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：刘爱芳负责论文构思，设计及撰写；罗磊和杨文龙负责论文修订、指导、质量控制与审校。
Advances of clinical trials related to Resmetirom as an approved new drug for metabolic dysfunction-associated steatohepatitis
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摘要: 代谢功能障碍相关脂肪性肝病是全球第一大肝病，严重危害公众健康，但一直缺乏获批的治疗药物。2024年3月14日，Resmetirom（瑞美替罗）成为全球首个美国食品药品监督管理局批准用于治疗代谢相关脂肪性肝炎（MASH）的药物。本文归纳和总结了Resmetirom治疗MASH的作用机制、相关临床试验设计及部分研究结果，并分析其不足和展望未来。基于目前已有的研究数据，Resmetirom在改善脂肪性肝炎和肝纤维化方面是有效的，但距离理想的MASH治疗药物还有不小的距离，期待更多、更有效的药物参与其中。Abstract: Metabolic dysfunction-associated steatotic liver disease is the largest liver disease around the world and is a serious public health hazard， but there has always been a lack of drugs approved for treatment. On March 14， 2024， Resmetirom became the first drug approved by the US Food and Drug Administration for the treatment of metabolic dysfunction-associated steatohepatitis （MASH）. This article summarizes the mechanism of action of Resmetirom in the treatment of MASH， related clinical trial designs， and some research results and analyzes shortcomings and future prospects. Current data have shown that Resmetirom is effective in improving steatohepatitis and liver fibrosis， but there is still a large gap between Resmetirom and the ideal drug for the treatment of MASH， and it is expected to develop more effective drugs for MASH.
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注： VLDL，极低密度脂蛋白；LDL，低密度脂蛋白；HDL，高密度脂蛋白。①通过调节甲状腺激素信号通路促进外源及内源脂肪降解为游离脂肪酸；②增加脂肪酸氧化；③促进线粒体生物发生和线粒体自噬，进而增加肝脏处理游离脂肪酸的能力；④通过减少VLDL的产生，增强肝内LDL受体的表达，调节胆固醇代谢，从而改善NASH。
图 1 Resmetirom的作用机制
Figure 1. Mechanism of action diagram of Resmetirom
注： MRE，磁共振弹性成像；VCTE，振动控制瞬态弹性成像；CAP，受控衰减参数。
图 2 MAESTRO-NASH研究设计
Figure 2. MAESTRO-NASH study design
图 3 MAESTRO-NAFLD-1/MAESTRO-NAFLD-OLE研究设计
Figure 3. MAESTRO-NAFLD-1/MAESTRO-NAFLD-OLE study design
表 1 Resmetirom相关临床试验汇总
Table 1. Summary of clinical trials related to Resmetirom
试验注册号/药物试验 临床阶段 进度 主要研究人群 受试者（例） 首要研究终点 研究结果/研究意义 完成时间 NCT01367873/
NCT01519531
Ⅰ 已完成 健康志愿者 72/48 评估其安全性、药代动力学、药效学 Resmetirom安全且耐受性良好，可显著降低LDL-C和TG水平 2011年10月/
2012年11月
NCT02912260 Ⅱ 已完成 NASH（F1～F3）、NAS≥4分且MRI-PDFF≥10%的成人 125 治疗第12周肝脏脂肪含量相对变化 Resmetirom可显著改善肝脂肪变性及肝纤维化 2018年4月 NCT03900429
（MAESTRO-NASH）
Ⅲ 正在
进行
NASH伴肝纤维化（F1b、F2或F3） 966 NAS下降≥2分且无肝纤维化的恶化，或肝纤维化程度改善≥1级且无NAS的恶化 Resmetirom可有效改善肝纤维化和缓解NASH 2028年1月 NCT04197479
（MAESTRO-NAFLD-1）
Ⅲ 已完成 NAFLD和NASH患者 1 143 治疗52周的安全性和耐受性 Resmetirom治疗NASH安全且耐受性良好 2023年1月 NCT04951219
（MAESTRO-NAFLD-OLE）
Ⅲ 招募中 NASH和NASH相关肝硬化患者 1 000 在MAESTRO-NAFLD-1基础上治疗2年的安全性和耐受性 评估Resmetirom治疗NASH长达2年的安全性和耐受性 2026年4月 NCT05500222
（MAESTRO-NASH-OUTCOMES）
Ⅲ 招募中 代偿良好的NASH肝硬化患者 700 36个月内复合临床结局事件发生率 评估Resmetirom治疗早期NASH伴肝硬化人群的疗效 2027年1月 
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