Intermittent Oral Dosing of Roxadustat in Peritoneal Dialysis Chronic Kidney Disease Patients with Anemia: A Randomized, Phase 3, Multicenter, Open-Label Study
Intermittent Oral Dosing of Roxadustat in Peritoneal Dialysis Chronic Kidney Disease Patients with Anemia: A Randomized, Phase 3, Multicenter, Open-Label Study
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DOI：
10.1111/1744-9987.12888
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发表时间：
2019-07-31
影响因子：
1.9
通讯作者：
Ueno, Mai
中科院分区：
文献类型：
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作者：
Akizawa, Tadao;Otsuka, Tetsuro;Ueno, Mai
Roxadustat是一种口服缺氧诱导因子脯氨酰羟化酶抑制剂，用于治疗慢性肾脏病（CKD）患者的贫血。这项III期、随机、开放标签、24周研究在既往接受过或未接受过红细胞生成刺激剂（ESA）治疗的日本CKD伴贫血腹膜透析（PD）患者中研究了罗沙度司他的疗效和安全性。先前未接受ESA治疗的患者（ESA初治组）随机接受罗沙杜司他治疗，起始剂量为50或70 mg，每周三次;先前接受ESA治疗的患者（ESA转换组）根据先前的ESA剂量从ESA转换为罗沙杜司他70或100 mg，每周三次。结果包括第18-24周时平均血红蛋白（Hb）水平在10-12 g/dL范围内的维持率、治疗结束时的累积应答率（Hb阈值，10.0 g/dL或10.5 g/dL; Hb增加，>= 1.0 g/dL）和第18-24周时的平均Hb水平。根据治疗后出现的不良事件（TEAE）的发生率评估安全性。入组了五十六例患者（ESA初治，n = 13; ESA转换，n = 43）。维持率（第18-24周）分别为92.3%（95% CI：64.0-99.8; ESA-初治）和74.4%（95% CI：58.8-86.5; ESA-转换）。ESA初治组的累积缓解率为100.0%。平均Hb水平（第18-24周）分别为11.05 g/dL（95% CI：10.67-11.42; ESA-初治）和10.93 g/dL（95% CI：10.73-11.13; ESA-转换）。常见的TEAE包括鼻咽炎和背痛。Roxadustat耐受性良好，可有效维持既往接受或未接受ESA治疗的PD CKD患者的目标Hb水平。
Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor developed to treat anemia in chronic kidney disease (CKD) patients. This Phase 3, randomized, open-label, 24-week study investigated the efficacy and safety of roxadustat in Japanese CKD patients with anemia on peritoneal dialysis (PD) who were previously treated or not treated with erythropoiesis stimulating agents (ESAs). Patients not previously receiving ESA (ESA-Naive group) were randomized to roxadustat at a starting dose of 50 or 70 mg three times weekly; patients previously receiving ESA (ESA-Converted group) switched from ESA to roxadustat 70 or 100 mg three times weekly depending on the prior ESA dose. Outcomes included maintenance rate of average hemoglobin (Hb) level within 10-12 g/dL at weeks 18-24, cumulative response rate at end of treatment (Hb thresholds, 10.0 g/dL or 10.5 g/dL; Hb increase, >= 1.0 g/dL), and average Hb levels at weeks 18-24. Safety was assessed by occurrence of treatment-emergent adverse events (TEAEs). Fifty-six patients were enrolled (ESA-Naive, n = 13; ESA-Converted, n = 43). Maintenance rates (weeks 18-24) were 92.3% (95% CI: 64.0-99.8; ESA-Naive) and 74.4% (95% CI: 58.8-86.5; ESA-Converted). Cumulative response rate was 100.0% in the ESA-Naive group. Average Hb levels (weeks 18-24) were 11.05 g/dL (95% CI: 10.67-11.42; ESA-Naive) and 10.93 g/dL (95% CI: 10.73-11.13; ESA-Converted). Common TEAEs included nasopharyngitis and back pain. Roxadustat was well tolerated and effective in maintaining target Hb levels in CKD patients on PD who were previously treated or not treated with ESA.