Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
Data Science, Development, Astellas Pharma, Inc., Tokyo, Japan.
Ther Apher Dial. 2021 Oct;25(5):575-585. doi: 10.1111/1744-9987.13609. Epub 2020 Dec 15.
Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of anemia in chronic kidney disease (CKD). Emerging evidence suggests that roxadustat may be beneficial for patients who inadequately respond to erythropoiesis-stimulating agents (ESAs). This post-hoc analysis of a Japanese, double-blind, randomized, phase 3 study in hemodialysis-dependent CKD patients treated with traditional ESAs assessed the impact of factors associated with ESA hyporesponsiveness on roxadustat and darbepoetin alfa (DA) doses required to maintain target hemoglobin. Endpoints included mean of average doses of roxadustat and DA per administration in the last 6 weeks (AAD/6W) by prior ESA-resistance index (ERI), iron repletion (transferrin saturation; ferritin), and high-sensitivity C-reactive protein (hs-CRP). Of 415 enrolled patients, 303 were randomized (roxadustat, n = 151; DA, n = 152). Weight-adjusted AAD/6W increased with increasing ERI for roxadustat (ERI <3.3, 0.89 mg/kg; ERI ≥8.4, 1.51 mg/kg) and DA (ERI <3.3, 0.26 μg/kg; ERI ≥8.4, 0.91 μg/kg); the weight-adjusted AAD/6W relative to within-arm mean AAD/6W showed a trend toward increased DA doses for the ERI ≥8.4 category (P = .089). AAD/6W remained stable for roxadustat but increased for DA with decreasing baseline iron repletion markers. The relationship between roxadustat doses and end of treatment (EoT) hs-CRP was not significant (estimated slope, -0.494; P = .814); a trend toward increased DA doses was observed with increasing EoT hs-CRP (estimated slope, 2.973; P = .075). Roxadustat doses required to maintain target hemoglobin appear to be less affected by factors that underlie ESA hyporesponsiveness, relative to DA; roxadustat may be beneficial for patients hyporesponsive to ESAs.
罗沙司他是一种口服低氧诱导因子脯氨酰羟化酶抑制剂，用于治疗慢性肾脏病（CKD）引起的贫血。新出现的证据表明，罗沙司他可能对接受促红细胞生成素刺激剂（ESA）治疗反应不足的患者有益。本项日本、双盲、随机、III 期研究的事后分析纳入了接受传统 ESA 治疗的血液透析依赖的 CKD 患者，评估了与 ESA 低反应性相关的因素对罗沙司他和达贝泊汀 α（DA）剂量的影响，以维持目标血红蛋白。主要终点包括根据既往 ESA 抵抗指数（ERI）、铁补充（转铁蛋白饱和度；铁蛋白）和高敏 C 反应蛋白（hs-CRP），最后 6 周（6W）的罗沙司他和 DA 平均剂量（AAD/6W）。共纳入 415 例患者，303 例患者被随机分组（罗沙司他组，n=151；DA 组，n=152）。对于罗沙司他，体重校正 AAD/6W 随 ERI 增加而增加（ERI＜3.3，0.89mg/kg；ERI≥8.4，1.51mg/kg），DA 也呈现同样趋势（ERI＜3.3，0.26μg/kg；ERI≥8.4，0.91μg/kg）；ERI≥8.4 组的体重校正 AAD/6W 相对于同组内平均 AAD/6W 呈增加趋势（P=0.089）。罗沙司他的 AAD/6W 保持稳定，而 DA 的 AAD/6W 随着基线铁补充标志物的减少而增加。罗沙司他剂量与治疗结束（EoT）时 hs-CRP 之间无显著相关性（估计斜率，-0.494；P=0.814）；随着 EoT hs-CRP 增加，DA 剂量呈增加趋势（估计斜率，2.973；P=0.075）。与 DA 相比，维持目标血红蛋白所需的罗沙司他剂量似乎较少受到 ESA 低反应性相关因素的影响；罗沙司他可能对 ESA 反应不足的患者有益。
