Department of Nephrology, Showa University School of Medicine, Tokyo, Japan
Department of Data Science, Yokohama City University, Yokohama, Japan.
J Am Soc Nephrol. 2020 Jul;31(7):1628-1639. doi: 10.1681/ASN.2019060623. Epub 2020 Jun 3.
Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved in China for dialysis-dependent CKD anemia.
This phase 3, 24-week, double-blind, double-dummy study evaluated roxadustat's noninferiority to darbepoetin alfa for hemodialysis-dependent CKD anemia. We randomly assigned Japanese patients to oral roxadustat three times weekly or to darbepoetin alfa injections once weekly, titrating doses to maintain hemoglobin between 10-12 g/dl. The primary end point was change of average hemoglobin from baseline to weeks 18-24 (Hb). Secondary end points were average hemoglobin and proportion of patients with hemoglobin between 10-12 g/dl (maintenance rate) at weeks 18-24, and iron parameters. Safety assessments included treatment-emergent adverse events and adjudicated ophthalmologic findings.
We randomly assigned 303 patients to roxadustat (=151) or darbepoetin alfa (=152). The difference between roxadustat and darbepoetin alfa in Hb was -0.02 g/dl (95% confidence interval, -0.18 to 0.15), confirming roxadustat's noninferiority to darbepoetin alfa. Average hemoglobin at weeks 18-24 with roxadustat was 10.99 g/dl (95% confidence interval: 10.88 to 11.10), confirming its efficacy. Among patients with one or more hemoglobin value during weeks 18-24, the maintenance rate was 95.2% with roxadustat and 91.3% with darbepoetin alfa. Serum iron, ferritin, and transferrin saturation remained clinically stable with roxadustat; transferrin and total iron binding capacity increased through week 4 before stabilizing. Common treatment-emergent adverse events were nasopharyngitis, shunt stenosis, diarrhea, contusion, and vomiting. The proportion of patients with new or worsening retinal hemorrhage was 32.4% with roxadustat and 36.6% with darbepoetin alfa. We observed no clinically meaningful changes in retinal thickness groups.
Roxadustat maintained hemoglobin within 10-12 g/dl in patients on hemodialysis and was noninferior to darbepoetin alfa. Treatment-emergent adverse events were consistent with previous reports.
A Study of Intermittent Oral Dosing of ASP1517 in Hemodialysis Chronic Kidney Disease Patients with Anemia, NCT02952092 (ClinicalTrials.gov).
罗沙司他是一种口服低氧诱导因子脯氨酰羟化酶抑制剂，已在中国获批用于治疗透析依赖型慢性肾脏病贫血。
这是一项 24 周、双盲、双模拟的 3 期研究，评估了罗沙司他治疗透析依赖型慢性肾脏病贫血的非劣效性，与每周一次的注射用达贝泊汀相比。我们将日本患者随机分配至口服罗沙司他每周 3 次或每周一次注射用达贝泊汀治疗，调整剂量以维持血红蛋白在 10-12 g/dl 之间。主要终点为从基线到第 18-24 周时平均血红蛋白的变化（Hb）。次要终点为第 18-24 周时平均血红蛋白和血红蛋白在 10-12 g/dl 之间的患者比例（维持率），以及铁参数。安全性评估包括治疗出现的不良事件和经判定的眼科检查结果。
我们将 303 例患者随机分配至罗沙司他（n=151）或达贝泊汀组（n=152）。罗沙司他和达贝泊汀在 Hb 上的差异为-0.02 g/dl（95%置信区间：-0.18 至 0.15），证实了罗沙司他非劣效于达贝泊汀。罗沙司他在第 18-24 周的平均血红蛋白为 10.99 g/dl（95%置信区间：10.88 至 11.10），证实了其疗效。在第 18-24 周有一次或多次血红蛋白值的患者中，罗沙司他的维持率为 95.2%，达贝泊汀为 91.3%。罗沙司他使血清铁、铁蛋白和转铁蛋白饱和度保持临床稳定；转铁蛋白和总铁结合力在第 4 周前增加，之后稳定。常见的治疗出现的不良事件包括鼻咽炎、分流狭窄、腹泻、挫伤和呕吐。罗沙司他组和达贝泊汀组新发或恶化的视网膜出血患者比例分别为 32.4%和 36.6%。我们观察到视网膜厚度组没有临床意义的变化。
罗沙司他使接受血液透析的患者的血红蛋白维持在 10-12 g/dl 之间，且非劣效于达贝泊汀。治疗出现的不良事件与之前的报告一致。
间歇性口服 ASP1517 治疗血液透析慢性肾脏病贫血患者的研究，NCT02952092（ClinicalTrials.gov）。
