生物仿制药重组人促红细胞生成素α治疗血液透析患者肾性贫血疗效的研究：一项多中心临床试验

Investigation of the efficacy of a biogeneric recombinant human erythropoietin alfa in the management of renal anemia in patients on hemodialysis: a multi-center clinical trial.

作者信息

Beiraghdar Fatemeh, Panahi Yunes, Einollahi Behzad, Nemati Eghlim, Ghadiani Mohammad Hassan, Sahebkar Amirhossein, Maghsoudi Nader, Marzony Eisa Tahmasbpour

机构信息

Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

出版信息

Clin Lab. 2012;58(7-8):737-45.

PMID:22997974

Abstract

BACKGROUND

Recombinant human erythropoietin (rHuEPO) is the cornerstone therapy for anemia associated with chronic kidney disease. However, not all patients with renal anemia receive sufficient doses of rHuEPO due to its high cost. The present trial aimed to evaluate the efficacy of Epolyrec, a biogeneric rHuEPO, in the management of renal anemia in patients on hemodialysis.

METHODS

Seventy-two patients with end stage renal disease (ESRD) who were receiving hemodialysis were assigned to receive Epolyrec subcutaneously at a dose of 40-80 IU/Kg in 2-3 divided doses after each dialysis session for 12 weeks. Hemoglobin, hematocrit, and CBC/DIFF together with biomarkers of iron status, renal function, and trace elements were evaluated at baseline and during the course of trial.

RESULTS

Hemoglobin concentrations and hematocrit progressively increased from baseline (8.45 +/- 1.42 mg/dL and 27.05 +/- 4.64% for hemoglobin and hematocrit, respectively) to the end of trial (10.56 +/- 1.93 and 34.06 +/- 6.70) (p < 0.001). RBC count (p = 0.026), reticulocyte count (p = 0.045), and MCV (p < 0.001) were also significantly increased at the end of trial (3.86 +/- 0.91x10(6)/microL, 0.78 +/- 0.31%, and 93.50 +/- 10.90 fL for RBC count, reticulocyte count, and MCV, respectively) compared to baseline (0.98 +/- 3.38, 0.18 +/- 0.63, and 89.75 +/- 9.35). Serum iron and ferritin were decreased while creatinine and phosphorous increased by the end of trial. No significant change was observed in WBC count, RDW, MCH, MCHC, BUN, PTH, Na, Ca, K, and Mg (p > 0.05). The frequencies of evaluated side effects were generally low and < 10%.

CONCLUSIONS

Epolyrec is clinically efficacious in the elevation of hemoglobin and hematocrit in anemic ESRD patients receiving hemodialysis. Future comparative trials are warranted to compare the efficacy and safety of Epolyrec to those of innovator products.

摘要

背景

重组人促红细胞生成素（rHuEPO）是治疗慢性肾脏病相关性贫血的基石疗法。然而，由于成本高昂，并非所有肾性贫血患者都能接受足够剂量的rHuEPO。本试验旨在评估生物仿制药Epolyrec治疗血液透析患者肾性贫血的疗效。

方法

72例接受血液透析的终末期肾病（ESRD）患者被分配接受Epolyrec皮下注射，剂量为40 - 80 IU/Kg，在每次透析后分2 - 3次给药，共12周。在基线期和试验过程中评估血红蛋白、血细胞比容、全血细胞计数/分类以及铁状态、肾功能和微量元素的生物标志物。

结果

血红蛋白浓度和血细胞比容从基线期（血红蛋白为8.45±1.42 mg/dL，血细胞比容为27.05±4.64%）逐渐增加至试验结束时（分别为10.56±1.93和34.06±6.70）（p < 0.001）。试验结束时红细胞计数（p = 0.026）、网织红细胞计数（p = 0.045）和平均红细胞体积（p < 0.001）也显著增加（红细胞计数、网织红细胞计数和平均红细胞体积分别为3.86±0.91x10(6)/μL、0.78±0.31%和93.50±10.90 fL），而基线期分别为0.98±3.38、0.18±0.63和89.75±9.35。试验结束时血清铁和铁蛋白降低，而肌酐和磷升高。白细胞计数、红细胞分布宽度、平均红细胞血红蛋白含量、平均红细胞血红蛋白浓度、血尿素氮、甲状旁腺激素、钠、钙、钾和镁无显著变化（p > 0.05）。评估的副作用发生率普遍较低，< 10%。