本文由小咖机器人翻译整理

期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2309000

摘要内容如下：

背景

非酒精性脂肪性肝炎（Nash）是一种尚无治疗方法的进行性肝病。Resmetirom是一种正在开发的口服、肝脏定向、甲状腺激素受体β-选择性激动剂，用于治疗伴有肝纤维化的Nash。

方法

我们正在进行一项正在进行的3期临床试验，研究对象为经活检证实的Nash成人患者，纤维化分期为F1b、F2或F3（分期范围从F0[无纤维化]到F4[肝硬化]）。患者以1:1:1的比例被随机分配接受每日一次剂量为80 mg或100 mg的Resmetirom或安慰剂。第52周的两个主要终点是Nash消退（包括非酒精性脂肪性肝病[NAFLD]活动评分减少≥2分；评分范围为0至8，评分越高表明疾病越严重，但纤维化没有恶化，并且纤维化改善（减少）至少一个阶段，但NAFLD活动评分没有恶化。

结果

总体而言，966名患者构成了主要分析人群（80 mg Resmetirom组322名，100 mg Resmetirom组323名，安慰剂组321名）。80 mg Resmetirom组中25.9%的患者和100 mg Resmetirom组中29.9%的患者达到Nash消退且纤维化无恶化，而安慰剂组中这一比例为9.7%（与安慰剂相比，两组均P<0.001）。80 mg Resmetirom组中有24.2%的患者和100 mg Resmetirom组中有25.9%的患者纤维化改善至少一个阶段，且NAFLD活动评分未恶化，而安慰剂组中有14.2%的患者纤维化改善（与安慰剂比较，P<0.001）。从基线到第24周，低密度脂蛋白胆固醇水平的变化在80 mg resmetirom组为-13.6%，在100 mg resmetirom组为-16.3%，而安慰剂组为0.1%（与安慰剂比较，P<0.001）。与安慰剂组相比，Resmetirom组出现腹泻和恶心的频率更高。各试验组的严重不良事件发生率相似:80 mg Resmetirom组为10.9%，100 mg Resmetirom组为12.7%，安慰剂组为11.5%。

结论

在Nash消退和至少一个阶段的肝纤维化改善方面，80 mg剂量和100 mg剂量的Resmetirom均优于安慰剂。（由牧歌制药公司（Madrigal Pharmaceuticals）资助；Maestro-Nash ClinicalTrials.gov编号：NCT03900429）。

英文原文如下：

Abstracts

BACKGROUND  Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatment. Resmetirom is an oral, liver-directed, thyroid hormone receptor beta-selective agonist in development for the treatment of NASH with liver fibrosis.

METHODS  We are conducting an ongoing phase 3 trial involving adults with biopsy-confirmed NASH and a fibrosis stage of F1B, F2, or F3 (stages range from F0 [no fibrosis] to F4 [cirrhosis]). Patients were randomly assigned in a 1:1:1 ratio to receive once-daily resmetirom at a dose of 80 mg or 100 mg or placebo. The two primary end points at week 52 were NASH resolution (including a reduction in the nonalcoholic fatty liver disease [NAFLD] activity score by ≥2 points; scores range from 0 to 8, with higher scores indicating more severe disease) with no worsening of fibrosis, and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.

RESULTS  Overall, 966 patients formed the primary analysis population (322 in the 80-mg resmetirom group, 323 in the 100-mg resmetirom group, and 321 in the placebo group). NASH resolution with no worsening of fibrosis was achieved in 25.9% of the patients in the 80-mg resmetirom group and 29.9% of those in the 100-mg resmetirom group, as compared with 9.7% of those in the placebo group (P<0.001 for both comparisons with placebo). Fibrosis improvement by at least one stage with no worsening of the NAFLD activity score was achieved in 24.2% of the patients in the 80-mg resmetirom group and 25.9% of those in the 100-mg resmetirom group, as compared with 14.2% of those in the placebo group (P<0.001 for both comparisons with placebo). The change in low-density lipoprotein cholesterol levels from baseline to week 24 was -13.6% in the 80-mg resmetirom group and -16.3% in the 100-mg resmetirom group, as compared with 0.1% in the placebo group (P<0.001 for both comparisons with placebo). Diarrhea and nausea were more frequent with resmetirom than with placebo. The incidence of serious adverse events was similar across trial groups: 10.9% in the 80-mg resmetirom group, 12.7% in the 100-mg resmetirom group, and 11.5% in the placebo group.

CONCLUSIONS  Both the 80-mg dose and the 100-mg dose of resmetirom were superior to placebo with respect to NASH resolution and improvement in liver fibrosis by at least one stage. (Funded by Madrigal Pharmaceuticals; MAESTRO-NASH ClinicalTrials.gov number, NCT03900429.).

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