生物类似性红细胞生成素治疗贫血（BEAT）-在接受血液透析的终末期肾病患者中将 EPREX® 转换为 EPIAO® 的 1:1 剂量转换的疗效和安全性：一项前瞻性、随机、双盲、平行组研究。

Biosimilar erythropoietin in anemia treatment (BEAT)-Efficacy and safety of a 1:1 dose conversion from EPREX® to EPIAO® in patients with end-stage renal disease on hemodialysis: A prospective, randomized, double blind, parallel group study.

机构信息

Medical Department, Shenyang Sunshine Pharmaceutical Co., Ltd., Shenyang Economy & Technology Department Zone, Shenyang, P.R.China.

State Educational Government-Financed Institution of Higher Professional Education "North-Western State Medical University named after I.I. Mechnikov" of the Ministry of Health and Social Development of the Russian Federation, Clinical Hospital named after Peter the Great, dialysis department, Saint Petersburg, Russia.

出版信息

Medicine (Baltimore). 2022 Nov 25;101(47):e31426. doi: 10.1097/MD.0000000000031426.

DOI:10.1097/MD.0000000000031426

PMID:36451454

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9704908/

Abstract

BACKGROUND

EPREX®/ERYPO®/PROCRIT® (epoetin alfa, Janssen-Cilag GmbH) was the first available recombinant human erythropoietin (rHuEPO) and was universally reference product as per the recommendation provided by European Medicines Agency. EPIAO® is a biosimilar formulation of EPREX®, and making it a 1:1 dose conversion from EPREX® according to recommendation of European Medicines Agency. This study evaluated the clinical efficacy and safety of EPIAO® in subjects with end-stage renal disease receiving hemodialysis after intravenous administration.

METHODS

This study was a multicenter, prospective, randomized, double-blind, parallel-group, 2-cohort, maintenance phase, therapeutic equivalence study to evaluate a 1:1 dose conversion from EPREX® to EPIAO® in terms of clinical efficacy and safety that was conducted at 20 sites in 2 countries in patients with end-stage renal disease on hemodialysis. Eligible subjects were treated with EPREX® (reference product of epoetin) for a period of at least 3 months before the treatment period, and then were randomly assigned to the group of EPREX® or EPIAO®. Primary endpoints were mean absolute change in hemoglobin level and mean absolute change in weekly epoetin dosage from baseline to 6 months after treatment with EPIAO®/EPREX® in parallel groups.

RESULTS

A total of 200 people received the random intervention and were included in the safety set. After 6, 9, and 12 months of treatment with EPIAO® or EPREX®, there were no significant differences in the hemoglobin levels of the 2 groups compared with baseline. The 95% confidence interval for the treatment difference was within the predetermined acceptable range: ±0.5 g/dL. There were no significant differences in the epoetin dosage of the 2 groups compared with the baseline. The 95% confidence interval for the treatment difference was within the predetermined acceptable range: ± 45 IU/kg. There were no significant differences in the incidence of adverse events between the EPIAO® and EPREX® groups. Most adverse events were mild to moderate and were reverted/resolved.

CONCLUSION

EPIAO® demonstrated promising effectiveness and manageable safety in patients with end-stage renal disease on hemodialysis.

摘要

背景

EPREX®/ERYPO®/PROCRIT®（聚乙二醇重组人促红细胞生成素，Janssen-Cilag GmbH）是首个上市的重组人促红细胞生成素（rHuEPO），并且根据欧洲药品管理局的建议，被普遍认为是参比制剂。EPIAO®是 EPREX®的生物类似药，根据欧洲药品管理局的建议，EPIAO®与 EPREX®可以进行 1:1 剂量转换。本研究评估了静脉给药后接受血液透析的终末期肾病患者使用 EPIAO®的临床疗效和安全性。

方法

本研究是一项多中心、前瞻性、随机、双盲、平行分组、2 队列、维持期、治疗等效性研究，在 2 个国家的 20 个中心进行，旨在评估终末期肾病血液透析患者从 EPREX®转换为 EPIAO®的 1:1 剂量转换在临床疗效和安全性方面的情况。纳入的受试者在治疗期前至少接受 EPREX®（促红细胞生成素的参比制剂）治疗 3 个月，然后随机分为 EPREX®或 EPIAO®组。主要终点为平行组中使用 EPIAO®/EPREX®治疗 6 个月后血红蛋白水平的平均绝对变化和每周促红细胞生成素剂量的平均绝对变化。

结果

共有 200 人接受随机干预并纳入安全性集。接受 EPIAO®或 EPREX®治疗 6、9 和 12 个月后，与基线相比，两组的血红蛋白水平无显著差异。治疗差异的 95%置信区间在预定的可接受范围内：±0.5 g/dL。与基线相比，两组的促红细胞生成素剂量无显著差异。治疗差异的 95%置信区间在预定的可接受范围内：±45 IU/kg。EPIAO®组和 EPREX®组的不良反应发生率无显著差异。大多数不良反应为轻度至中度，且可逆转/缓解。