Division of Nephrology, Department of Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento, University of Campania "Luigi Vanvitelli", Via M. Longo 50, 80138, Naples, Italy.
ASL Cagliari, Cagliari, Italy.
Clin Drug Investig. 2017 Oct;37(10):965-973. doi: 10.1007/s40261-017-0562-8.
In hemodialysis (HD), switching from erythropoiesis-stimulating agent (ESA) originators to biosimilars is associated with the need for doses approximately 10% higher, according to industry-driven studies.
The aim of this study was to evaluate the efficacy on anemia control of switching from ESA originators to biosimilars in daily clinical practice.
We retrospectively selected consecutive HD patients receiving stable intravenous ESA doses, and who had not been transfused in the previous 6 months, from 12 non-profit Italian centers. Patients switched from originators to biosimilars (n = 163) were matched with those maintained on ESA originators (n = 163) using a propensity score approach. The study duration was 24 weeks, and the primary endpoint was the mean dose difference (MDD), defined as the difference between the switch and control groups of ESA dose changes during the study (time-weighted average ESA dose minus baseline ESA dose).
Age (70 ± 13 years), male sex (63%), diabetes (29%), history of cardiovascular disease (40%), body weight (68 ± 14 kg), vascular access (86% arteriovenous fistula), hemoglobin [Hb] (11.2 ± 0.9 g/dL) and ESA dose (8504 ± 6370 IU/week) were similar in the two groups. Hb remained unchanged during the study in both groups. Conversely, ESA dose remained unchanged in the control group and progressively increased in the switch group from week 8 to 24. The time-weighted average of the ESA dose was higher in the switch group than in the control group (10,503 ± 7389 vs. 7981 ± 5858 IU/week; p = 0.001), leading to a significant MDD of 2423 IU/week (95% confidence interval [CI] 1615-3321), corresponding to a 39.6% (95% CI 24.7-54.6) higher dose of biosimilars compared with originators. The time-weighted average of Hb was 0.2 g/dL lower in the switch group, with a more frequent ESA hyporesponsiveness (14.7 vs. 2.5%). Iron parameters and other resistance factors remained unchanged.
In stable dialysis patients, switching from ESA originators to biosimilars requires 40% higher doses to maintain anemia control.
在血液透析（HD）中，根据行业驱动的研究，从促红细胞生成素刺激剂（ESA）原研药转换为生物类似药与需要更高约 10%的剂量相关。
本研究旨在评估在日常临床实践中从 ESA 原研药转换为生物类似药对贫血控制的疗效。
我们从 12 家非营利性意大利中心回顾性选择了接受稳定静脉 ESA 剂量且在前 6 个月内未输血的连续 HD 患者。从 ESA 原研药转换为生物类似药的患者（n=163）通过倾向评分匹配与继续接受 ESA 原研药的患者（n=163）进行匹配。研究持续 24 周，主要终点是平均剂量差异（MDD），定义为研究期间转换组和对照组 ESA 剂量变化的差异（时间加权平均 ESA 剂量减去基线 ESA 剂量）。
两组患者的年龄（70±13 岁）、男性（63%）、糖尿病（29%）、心血管疾病史（40%）、体重（68±14kg）、血管通路（86%动静脉瘘）、血红蛋白[Hb]（11.2±0.9g/dL）和 ESA 剂量（8504±6370IU/周）相似。两组患者在研究期间 Hb 均保持不变。相反，对照组 ESA 剂量保持不变，而转换组从第 8 周到第 24 周逐渐增加。转换组的时间加权平均 ESA 剂量高于对照组（10503±7389 比 7981±5858IU/周；p=0.001），导致每周 2423IU 的显著 MDD（95%置信区间[CI]1615-3321），相当于与原研药相比，生物类似药的剂量增加了 39.6%（95%CI 24.7-54.6）。转换组的时间加权平均 Hb 低 0.2g/dL，ESA 低反应性更为频繁（14.7 比 2.5%）。铁参数和其他耐药因素保持不变。
在稳定的透析患者中，从 ESA 原研药转换为生物类似药需要增加 40%的剂量才能维持贫血控制。
