Health-Related quality of life (HRQL) assessments in a 52-Week, Double-Blind, randomized, Placebo-Controlled phase 3 study of resmetirom (MGL-3196) in patients with metabolic dysfunction associated steatohepatitis (MASH) and fibrosis

IF 12.9 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Hepatology Pub Date : 2024-09-09 DOI:10.1097/hep.0000000000001084

Zobair M. Younossi, Maria Stepanova, Andrei Racila, Linda Henry, Dominic Labriola, Rebecca Taub, Fatema Nader

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引用次数: 0

Abstract

Background/Aims: Resmetirom, liver directed thyroid-hormone receptor-β agonist, received approval for MASH treatment. We assessed HRQL in MASH patients treated with resmetirom. Methods: Non-cirrhotic MASH/NASH patients with confirmed/suspected fibrosis were enrolled in a 54-month double-blind randomized placebo-controlled Phase 3 clinical trial with serial biopsy assessments (MAESTRO-NASH, NCT03900429) at baseline and Week 52. HRQL was assessed using Chronic Liver Disease Questionnaire-NASH (CLDQ-NAFLD) and Liver Disease Quality of Life (LDQOL). Baseline HRQL score changes by treatment group (resmetirom 80 mg, resmetirom 100 mg or placebo) and histological response (improvement of fibrosis without worsening of NAS or resolution of MASH/NASH without worsening of fibrosis) were compared after 52 weeks. Results: Included were 966 ITT patients: 323 received resmetirom 100 mg, 322 resmetirom 80 mg, 321 placebo. By weeks 24 and 52, patients receiving 80 or 100 mg resmetirom experienced HRQL improvement CLDQ-NAFLD worry domain (mean +0.21 to +0.24, p<0.05). At week 52, subjects who met histologic endpoints after treatment with resmetirom (100 mg and 80 mg pooled) experienced HRQL improvement in CLDQ-NAFLD Worry +0.46 (41% met MCID), LDQOL domains: Role Emotional +3.0 (28% met MCID), Health Distress +8.1 (38% MCID), Stigma +3.5 (39% MCID) and total LDQOL +2.2 (35% MCID) (all p<0.05). Similar improvements noted in histologic responders from 100 mg or 80 mg resmetirom groups when separated- no improvements in placebo or nonresponders. Baseline F3 histologic responders had similar/more pronounced HRQL improvements. Conclusions: MASH/NASH patients with fibrosis improvement or resolution of MASH with resmetirom experienced clinically meaningful and statistically significant HRQL improvements.

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在代谢功能障碍相关性脂肪性肝炎（MASH）和肝纤维化患者中开展的为期 52 周的瑞美替罗（MGL-3196）双盲、随机、安慰剂对照 3 期研究中进行与健康相关的生活质量 (HRQL) 评估

背景/目的：肝脏定向甲状腺激素受体-β激动剂雷美替罗被批准用于MASH治疗。我们评估了接受瑞美替罗治疗的 MASH 患者的 HRQL。方法确诊/疑似纤维化的非肝硬化 MASH/NASH 患者参加了为期 54 个月的双盲随机安慰剂对照 3 期临床试验，并在基线和第 52 周进行了连续活检评估（MAESTRO-NASH，NCT03900429）。HRQL采用慢性肝病问卷-NASH（CLDQ-NAFLD）和肝病生活质量（LDQOL）进行评估。比较52周后各治疗组（瑞美替罗80毫克、瑞美替罗100毫克或安慰剂）的基线HRQL评分变化和组织学反应（纤维化改善而NAS不恶化或MASH/NASH缓解而纤维化不恶化）。结果纳入了 966 名 ITT 患者：其中 323 人接受了 100 毫克的瑞美替罗治疗，322 人接受了 80 毫克的瑞美替罗治疗，321 人接受了安慰剂治疗。在第24周和第52周，接受80或100毫克雷美替罗治疗的患者CLDQ-NAFLD担忧域的HRQL有所改善（平均+0.21至+0.24，p<0.05）。在第 52 周，接受瑞美替罗（100 毫克和 80 毫克合用）治疗后达到组织学终点的受试者在 CLDQ-NAFLD 担忧 +0.46（41% 达到 MCID）、LDQOL 领域的 HRQL 均有所改善：角色情感 +3.0（28% 达到 MCID）、健康困扰 +8.1（38% 达到 MCID）、耻辱感 +3.5（39% 达到 MCID）和总 LDQOL +2.2（35% 达到 MCID）（所有 p<0.05）。将 100 毫克或 80 毫克雷美替罗组的组织学应答者区分开后，也发现了类似的改善--安慰剂组或无应答者没有改善。基线 F3 组织学应答者的 HRQL 改善相似/更明显。结论MASH/NASH患者在使用雷美替罗后纤维化得到改善或MASH得到缓解，其HRQL改善具有临床意义和统计学意义。

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来源期刊

Hepatology 医学-胃肠肝病学

CiteScore

27.50

自引率

3.70%

发文量

609

审稿时长

1 months

期刊介绍： HEPATOLOGY is recognized as the leading publication in the field of liver disease. It features original, peer-reviewed articles covering various aspects of liver structure, function, and disease. The journal's distinguished Editorial Board carefully selects the best articles each month, focusing on topics including immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases, liver cancer, and drug metabolism.