在转甲状腺素蛋白淀粉样变性心肌病3期APOLLO - B研究的巴西亚组人群中进行的帕替西兰治疗：事后分析。

Patisiran Treatment in the Brazilian Subpopulation of the Phase 3 APOLLO-B Study in Transthyretin Amyloidosis with Cardiomyopathy: Post Hoc Analysis.

作者信息

Mesquita Claudio Tinoco, Schwartzmann Pedro, Correia Edileide Barros, Simões Marcus V, Biolo Andreia, Duque Daniel Rodriguez, Jay Patrick Y, Fernandes Fábio

机构信息

Hospital Pró-Cardíaco, Rio de Janeiro, RJ - Brasil.

Universidade Federal Fluminense, Niterói, RJ - Brasil.

出版信息

Arq Bras Cardiol. 2025 Mar;122(4):e20240568. doi: 10.36660/abc.20240568.

DOI:10.36660/abc.20240568

PMID:40243852

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12107767/

Abstract

BACKGROUND

Patisiran rapidly knocked down transthyretin and preserved functional capacity in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) in the global Phase 3 APOLLO-B study (NCT03997383).

OBJECTIVES

To evaluate patisiran efficacy and safety in post hoc analysis of the Brazilian subpopulation of APOLLO-B.

METHODS

Patients were randomized 1:1 to patisiran 0.3 mg/kg or placebo every 3 weeks for 12 months. The primary endpoint was the change from baseline (CFB) in functional capacity (6-minute walk test [6MWT]) at Month 12. Secondary endpoints included CFB to Month 12 in the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score. Exploratory endpoints included CFB in cardiac biomarkers and Perugini grade of cardiac uptake during technetium-99m scintigraphy.

RESULTS

Forty-two patients enrolled in Brazil (patisiran, n=20; placebo, n=22). Patisiran showed benefit in 6MWT and KCCQ-OS scores vs. placebo; CFB (95% confidence interval [CI]) in 6MWT (median) and KCCQ-OS scores (least squares mean) was -2.0 m (-58.5, 42.9) and 9.37 (1.93, 16.81) points with patisiran vs. -30.1 m (-72.2, 3.5) and 2.62 (-4.68, 9.92) points for placebo. For cardiac biomarkers, the mean fold-change from baseline (95% CI) for N-terminal prohormone B-type natriuretic peptide and troponin I was 1.31 (1.06, 1.61) and 1.12 (0.94, 1.34) for patisiran, and 1.71 (1.39, 2.10) and 1.28 (1.08, 1.53) for placebo, respectively. Perugini grade improved in 11/18 (61.1%) and 0/10 evaluable patients with patisiran and placebo, respectively. There were no deaths in the patisiran group vs. 3 in the placebo group.

摘要

背景

在全球3期APOLLO - B研究（NCT03997383）中，帕替沙兰可迅速降低转甲状腺素蛋白水平，并保留转甲状腺素蛋白淀粉样变心肌病（ATTR - CM）患者的功能能力。

目的

在APOLLO - B研究巴西亚组的事后分析中评估帕替沙兰的疗效和安全性。

方法

患者按1:1随机分组，每3周接受一次0.3mg/kg的帕替沙兰或安慰剂治疗，共12个月。主要终点是第12个月时功能能力（6分钟步行试验[6MWT]）相对于基线的变化（CFB）。次要终点包括堪萨斯城心肌病问卷 - 总体总结（KCCQ - OS）评分至第12个月时的CFB。探索性终点包括心脏生物标志物的CFB以及锝 - 99m闪烁显像期间的心脏摄取佩鲁吉尼分级。

结果

42名患者在巴西入组（帕替沙兰组，n = 20；安慰剂组，n = 22）。与安慰剂相比，帕替沙兰在6MWT和KCCQ - OS评分方面显示出益处；帕替沙兰组6MWT（中位数）和KCCQ - OS评分（最小二乘均值）的CFB（95%置信区间[CI]）分别为 - 2.0米（ - 58.5，42.9）和9.37（1.93，16.81）分，而安慰剂组分别为 - 30.1米（ - 72.2，3.5）和2.62（ - 4.68，9.92）分。对于心脏生物标志物，帕替沙兰组N末端B型利钠肽原和肌钙蛋白I相对于基线的平均变化倍数（95%CI）分别为1.31（1.06，1.61）和1.12（0.94，1.34），安慰剂组分别为1.71（1.39，2.10）和1.28（1.08，1.53）。帕替沙兰组11/18（61.1%）可评估患者的佩鲁吉尼分级得到改善，安慰剂组为0/10。帕替沙兰组无死亡病例，而安慰剂组有3例死亡。