上海交通大学医学院附属瑞金医院陈楠研究组发现，口服罗沙司他对中国透析患者贫血的治疗效果并不优于标准疗法。2019年9月12日出版的《新英格兰医学杂志》发表了该项成果。

罗沙司他是一种口服低氧诱导因子脯氨酰羟化酶抑制剂，刺激红细胞生成和调节铁代谢。在接受透析的患者中，罗沙司他与标准疗法（阿法依泊汀）相比，其有效性和安全性仍有待考证。

在中国进行的一项试验中，研究组共招募了305名患者，均接受过透析和促红细胞生成素治疗至少6周，平均基线血红蛋白水平为每分升10.4 g。按2：1将患者随机分组，204名每周接受3次罗沙司他治疗，101名进行促红细胞生成素治疗，为期26周。除作为抢救治疗外，不使用肠外铁。

治疗第23-27周，罗沙司他组血红蛋白水平平均增长了0.7±1.1 g/dl，大于阿法依泊汀组（0.5±1.0 g/dl），但无统计学差异。与阿法依泊汀相比，罗沙司他提高了转铁蛋白水平，维持血清铁水平，降低了转铁蛋白饱和度。在第27周，罗沙司他组总胆固醇和低密度脂蛋白胆固醇水平的下降幅度均大于阿法依泊汀组。罗沙司他组的铁调节蛋白水平平均降低了30.2 ng/ml，而阿法依泊汀组为2.3 ng/ml。罗沙司他组高钾血症和上呼吸道感染发生率较高，而阿法依泊汀组高血压发生率较高。

综上，口服罗沙司他对中国透析患者贫血的治疗效果并不优于肠外注射阿法依泊汀。

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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 Treatment for Anemia in Patients Undergoing Long-Term Dialysis

Author: Nan Chen, M.D., Chuanming Hao, M.D., Ph.D., Bi-Cheng Liu, M.D., Ph.D., Hongli Lin, M.D., Ph.D., Caili Wang, B.Sc., Changying Xing, M.D., Ph.D., Xinling Liang, M.D., Ph.D., Gengru Jiang, M.D., Zhengrong Liu, M.Sc., Xuemei Li, M.D., Ph.D., Li Zuo, M.D., Ph.D., Laimin Luo, M.Sc., Jianqin Wang, Ph.D., Ming-hui Zhao, Ph.D., Zhihong Liu, M.D., Guang-Yan Cai, M.D., Ph.D., Li Hao, M.Sc., 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 is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Additional data are needed regarding the effectiveness and safety of roxadustat as compared with standard therapy (epoetin alfa) for the treatment of anemia in patients undergoing dialysis.

METHODS
In a trial conducted in China, we randomly assigned (in a 2:1 ratio) patients who had been undergoing dialysis and erythropoiesis-stimulating agent therapy with epoetin alfa for at least 6 weeks to receive roxadustat or epoetin alfa three times per week for 26 weeks. Parenteral iron was withheld except as rescue therapy. The primary end point was the mean change in hemoglobin level from baseline to the average level during weeks 23 through 27. Noninferiority of roxadustat would be established if the lower boundary of the two-sided 95% confidence interval for the difference between the values in the roxadustat group and epoetin alfa group was greater than or equal to −1.0 g per deciliter. Patients in each group had doses adjusted to reach a hemoglobin level of 10.0 to 12.0 g per deciliter. Safety was assessed by analysis of adverse events and clinical laboratory values.

RESULTS
A total of 305 patients underwent randomization (204 in the roxadustat group and 101 in the epoetin alfa group), and 256 patients (162 and 94, respectively) completed the 26-week treatment period. The mean baseline hemoglobin level was 10.4 g per deciliter. Roxadustat led to a numerically greater mean (±SD) change in hemoglobin level from baseline to weeks 23 through 27 (0.7±1.1 g per deciliter) than epoetin alfa (0.5±1.0 g per deciliter) and was statistically noninferior (difference, 0.2±1.2 g per deciliter; 95% confidence interval [CI], −0.02 to 0.5). As compared with epoetin alfa, roxadustat increased the transferrin level (difference, 0.43 g per liter; 95% CI, 0.32 to 0.53), maintained the serum iron level (difference, 25 μg per deciliter; 95% CI, 17 to 33), and attenuated decreases in the transferrin saturation (difference, 4.2 percentage points; 95% CI, 1.5 to 6.9). At week 27, the decrease in total cholesterol was greater with roxadustat than with epoetin alfa (difference, −22 mg per deciliter; 95% CI, −29 to −16), as was the decrease in low-density lipoprotein cholesterol (difference, −18 mg per deciliter; 95% CI, −23 to −13). Roxadustat was associated with a mean reduction in hepcidin of 30.2 ng per milliliter (95% CI, −64.8 to −13.6), as compared with 2.3 ng per milliliter (95% CI, −51.6 to 6.2) in the epoetin alfa group. Hyperkalemia and upper respiratory infection occurred at a higher frequency in the roxadustat group, and hypertension occurred at a higher frequency in the epoetin alfa group.

CONCLUSIONS
Oral roxadustat was noninferior to parenteral epoetin alfa as therapy for anemia in Chinese patients undergoing dialysis. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652806. opens in new tab.)

DOI: 10.1056/NEJMoa1901713

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1901713