From the Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (N.C.), and the Division of Nephrology, Huashan Hospital Fudan University (C.H.), Shanghai, the Department of Nephrology, People's Hospital of Guangxi Zhuang Autonomous Region (X.P.), and the Department of Nephrology, First Affiliated Hospital of Guangxi Medical University (Y.L.), Nanning, the First Affiliated Hospital of Dalian Medical University, Dalian (H.L.), the Department of Nephrology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an (A.Y.), the Department of Nephrology, Second Hospital of Anhui Medical University, Hefei (L.H.), West China Hospital Sichuan University, Chengdu (Y.T.), the Division of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences (X.L.), and the Renal Division, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research (Z.L.), Guangzhou, the Department of Nephrology, First Affiliated Hospital (Jiangsu Province Hospital), Nanjing Medical University (C.X.), and the Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine (B.-C.L.), Nanjing, First Affiliated Hospital of Zhejiang University, Hangzhou (J.C.), First Affiliated Hospital of Nanchang University, Nanchang (L.L.), and the Department of Nephrology, Peking University People's Hospital, Beijing (L.Z.) - all in China; and FibroGen, San Francisco (R.L., C.W., C.L., T.N., L.S., K.-H.P.Y.).
N Engl J Med. 2019 Sep 12;381(11):1001-1010. doi: 10.1056/NEJMoa1813599. Epub 2019 Jul 24.
Roxadustat (FG-4592) is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase that stimulates erythropoiesis and regulates iron metabolism. In phase 2 studies involving patients with chronic kidney disease, roxadustat increased levels of endogenous erythropoietin to within or near the physiologic range, along with increasing hemoglobin levels and improving iron homeostasis. Additional data are needed regarding the efficacy and safety of roxadustat for the treatment of anemia in patients with chronic kidney disease who are not undergoing dialysis.
In this phase 3 trial conducted at 29 sites in China, we randomly assigned 154 patients with chronic kidney disease in a 2:1 ratio to receive roxadustat or placebo three times a week for 8 weeks in a double-blind manner. All the patients had a hemoglobin level of 7.0 to 10.0 g per deciliter at baseline. The randomized phase of the trial was followed by an 18-week open-label period in which all the patients received roxadustat; parenteral iron was withheld. The primary end point was the mean change from baseline in the hemoglobin level, averaged over weeks 7 through 9.
During the primary-analysis period, the mean (±SD) change from baseline in the hemoglobin level was an increase of 1.9±1.2 g per deciliter in the roxadustat group and a decrease of 0.4±0.8 g per deciliter in the placebo group (P<0.001). The mean reduction from baseline in the hepcidin level (associated with greater iron availability) was 56.14±63.40 ng per milliliter in the roxadustat group and 15.10±48.06 ng per milliliter in the placebo group. The reduction from baseline in the total cholesterol level was 40.6 mg per deciliter in the roxadustat group and 7.7 mg per deciliter in the placebo group. Hyperkalemia and metabolic acidosis occurred more frequently in the roxadustat group than in the placebo group. The efficacy of roxadustat in hemoglobin correction and maintenance was maintained during the 18-week open-label period.
In Chinese patients with chronic kidney disease who were not undergoing dialysis, those in the roxadustat group had a higher mean hemoglobin level than those in the placebo group after 8 weeks. During the 18-week open-label phase of the trial, roxadustat was associated with continued efficacy. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652819.).
罗沙司他（FG-4592）是一种口服低氧诱导因子（HIF）脯氨酰羟化酶抑制剂，可刺激红细胞生成并调节铁代谢。在涉及慢性肾脏病患者的 2 期研究中，罗沙司他将内源性促红细胞生成素水平提高到生理范围内或接近生理范围，同时提高血红蛋白水平并改善铁稳态。还需要更多的数据来评估罗沙司他治疗未接受透析的慢性肾脏病患者贫血的疗效和安全性。
在这项在中国 29 个地点进行的 3 期试验中，我们以 2:1 的比例将 154 例慢性肾脏病患者随机分为罗沙司他组或安慰剂组，两组患者在 8 周内每周接受 3 次双盲治疗。所有患者在基线时的血红蛋白水平为 7.0 至 10.0 g/dL。试验的随机阶段之后是 18 周的开放标签期，所有患者均接受罗沙司他治疗；暂停使用静脉铁剂。主要终点是第 7 周至第 9 周期间血红蛋白水平的平均变化。
在主要分析期间，罗沙司他组的血红蛋白水平较基线平均升高 1.9±1.2 g/dL，安慰剂组平均下降 0.4±0.8 g/dL（P<0.001）。罗沙司他组铁调素水平（与铁供应增加相关）较基线平均降低 56.14±63.40ng/ml，安慰剂组降低 15.10±48.06ng/ml。罗沙司他组总胆固醇水平较基线降低 40.6mg/dL，安慰剂组降低 7.7mg/dL。罗沙司他组高钾血症和代谢性酸中毒的发生率高于安慰剂组。在 18 周的开放标签期内，罗沙司他在血红蛋白校正和维持方面的疗效保持不变。
在未接受透析的中国慢性肾脏病患者中，罗沙司他组在 8 周后血红蛋白水平高于安慰剂组。在试验的 18 周开放标签阶段，罗沙司他仍具有持续疗效。（由 FibroGen 和 FibroGen [中国]医学技术发展公司资助；ClinicalTrials.gov 编号，NCT02652819）。
