上海交通大学医学院附属瑞金医院陈楠研究组9月12日在《新英格兰医学杂志》发表论文，分析了罗沙司他治疗未接受透析的慢性肾病患者贫血的疗效和安全性。

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，能刺激红细胞生成和调节铁代谢。在涉及慢性肾脏病患者的临床2期研究中，罗沙司他将内源性促红细胞生成素的水平提高到生理范围内或接近生理范围，同时增加血红蛋白水平和改善铁稳态。关于罗沙司他治疗未接受透析的慢性肾病患者贫血的疗效和安全性目前还未确定。

这项在中国29个地点进行的3期临床试验中，研究组采用双盲法按2：1随机分配154名慢性肾脏疾病患者每周接受三次罗沙司他或安慰剂治疗，为期8周。所有患者的血红蛋白基线水平为每分升7.0-10.0克。试验的随机阶段之后是一个18周的开放标记期，所有患者接受罗沙司他治疗，不使用肠外铁。

在初步分析期间，罗沙司他组的血红蛋白水平与基线相比平均每分升增加1.9±1.2 g，安慰剂组每分升减少0.4±0.8 g，差异显著。罗沙司他组铁调节蛋白水平（与更高的铁利用率相关）与基线相比平均降幅为56.14±63.40 ng/ml，安慰剂组为15.10±48.06 ng/ml。罗沙司他组总胆固醇水平较基线下降40.6 mg/dl，安慰剂组为7.7 mg/dl。罗沙司他组高钾血症和代谢性酸中毒发生率高于安慰剂组。在18周的开放标记期内，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，罗沙司他组治疗8周后的平均血红蛋白水平高于安慰剂组，且在试验的18周开放标记期，罗沙司他与持续疗效显著相关。

更多阅读

陈楠，博士，现为瑞金医院主任医师。法国国家医学科学院院士、主任医师、教授，擅长：原发、继发性肾小球疾病（遗传性肾炎、系统性小血管炎等），肾小管间质疾病，急慢性肾衰竭和血液净化治疗等。（据上海交通大学医学院附属瑞金医院）

附：英文原文

Title: Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis

Author: Nan Chen, M.D., Chuanming Hao, M.D., Ph.D., Xiaomei Peng, B.Sc., Hongli Lin, M.D., Ph.D., Aiping Yin, Ph.D., Li Hao, M.Sc., Ye Tao, M.D., Xinling Liang, M.D., Ph.D., Zhengrong Liu, M.Sc., Changying Xing, M.D., Ph.D., Jianghua Chen, M.Sc., Laimin Luo, M.Sc., Li Zuo, M.D., Ph.D., Yunhua Liao, M.Sc., Bi-Cheng Liu, M.D., Ph.D., Robert Leong, M.D., Chunrong Wang, M.D., Cameron Liu, Ph.D., Thomas Neff, Lynda Szczech, M.D., M.S.C.E., and Kin-Hung P. Yu, M.D.

Issue&Volume: Vol 381 No 11

Abstract: 

BACKGROUND
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.

METHODS
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.

RESULTS
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.

CONCLUSIONS
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. opens in new tab.)

DOI: 10.1056/NEJMoa1813599

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1813599