Coyne Daniel W, Roger Simon D, Shin Sug Kyun, Kim Sung Gyun, Cadena Andres A, Moustafa Moustafa A, Chan Tak Mao, Besarab Anatole, Chou Willis, Bradley Charles, Eyassu Meraf, Leong Robert, Lee Tyson T, Saikali Khalil G, Szczech Lynda, Yu Kin-Hung P
Division of Nephrology, Washington University School of Medicine, St. Louis, Missouri, USA.
Renal Unit, Renal Research, Gosford, NSW, Australia.
Kidney Int Rep. 2020 Dec 5;6(3):624-635. doi: 10.1016/j.ekir.2020.11.034. eCollection 2021 Mar.
Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and improves iron metabolism. We assessed the efficacy and tolerability of roxadustat in patients with chronic kidney disease (CKD)-related anemia not on dialysis.
ANDES was a global Phase 3 randomized study in which adults with stage 3-5 CKD not on dialysis received roxadustat or placebo. Patients were initially dosed thrice weekly; dose was titrated to achieve a hemoglobin level ≥11.0 g/dl, followed by titration for maintenance. The primary endpoints were change in hemoglobin (weeks 28-52) and proportion of patients achieving a hemoglobin response (hemoglobin ≥11.0 g/dl and increase ≥1.0 g/dl [baseline >8.0 g/dl], or increase ≥2.0 g/dl [baseline ≤8.0 g/dl]) (week 24). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were recorded.
In roxadustat (n = 616) and placebo (n = 306) groups, hemoglobin mean (SD) change from baseline over weeks 28-52 was significantly larger for roxadustat (2.00 [0.95]) versus placebo (0.16 [0.90]), corresponding to least-squares mean difference of 1.85 g/dl (95% confidence interval [CI] 1.74-1.97; 0.0001). The proportion of patients achieving a response at week 24 was larger for roxadustat (86.0%; 95% CI 83.0%-88.7%) versus placebo (6.6%; 95% CI 4.1%-9.9%; 0.0001). The proportion of patients receiving rescue therapy at week 52 was smaller for roxadustat (8.9%) versus placebo (28.9%); hazard ratio, 0.19 (95% CI 0.14-0.28; .0001). The incidences of TEAEs and TESAEs were comparable.
This study showed that roxadustat corrected and maintained hemoglobin and was well tolerated in patients with CKD-related anemia not on dialysis (ClinicalTrials.gov NCT01750190).
罗沙司他是一种口服的低氧诱导因子脯氨酰羟化酶抑制剂，可刺激红细胞生成并改善铁代谢。我们评估了罗沙司他在未接受透析的慢性肾脏病（CKD）相关性贫血患者中的疗效和耐受性。
ANDES是一项全球3期随机研究，其中未接受透析的3-5期CKD成人患者接受罗沙司他或安慰剂治疗。患者最初每周给药三次；剂量滴定以达到血红蛋白水平≥11.0 g/dl，随后进行维持滴定。主要终点为血红蛋白变化（第28 - 52周）和达到血红蛋白反应的患者比例（血红蛋白≥11.0 g/dl且增加≥1.0 g/dl[基线>8.0 g/dl]，或增加≥2.0 g/dl[基线≤8.0 g/dl]）（第24周）。记录治疗中出现的不良事件（TEAE）和严重不良事件（TESAEs）。
在罗沙司他组（n = 616）和安慰剂组（n = 306）中，罗沙司他组在第28 - 52周血红蛋白从基线的平均（标准差）变化（2.00[0.95]）显著大于安慰剂组（0.16[0.90]），最小二乘平均差异为1.85 g/dl（95%置信区间[CI]1.74 - 1.97；P < 0.0001）。罗沙司他组在第24周达到反应的患者比例（86.0%；95%CI 83.0% - 88.7%）大于安慰剂组（6.6%；95%CI 4.1% - 9.9%；P < 0.0001）。罗沙司他组在第52周接受挽救治疗的患者比例（8.9%）小于安慰剂组（28.9%）；风险比为0.19（95%CI 0.14 -
