UOSD Documentazione Scientifica/Scientific Research, Department of Epidemiology, Lazio Regional Health Service, Via Cristoforo Colombo, 112, Scale A-III Plan, 00147, Rome, Italy.
J Nephrol. 2018 Jun;31(3):321-332. doi: 10.1007/s40620-017-0419-5. Epub 2017 Jun 23.
Several Erythropoiesis-stimulating agents (ESAs) are available to treat anemia in patients with chronic kidney disease (CKD). Questions about the comparability of such therapeutic options are not purely a regulatory or economical matter. Appropriate use of originator or biosimilar in these patients need to be supported by clinical data. Regarding the prevention of blood transfusion, reduction of fatigue, breathlessness and mortality or cardiovascular events, a summary of the comparative efficacy and safety data of these drugs is lacking.
We performed a systematic literature search of CENTRAL, PubMed, and Embase through November 11, 2015. Our inclusion criteria encompassed randomized, controlled clinical trials that evaluated the comparative effectiveness of different ESAs originators and/or biosimilar. The considered participants were adults aged 18 years or older with anemia due to CKD. The overall quality of evidence was assessed using the GRADE system.
We identified 30 eligible studies including 7843 patients with CKD, and 21/30 studies included patients using hemodialysis or peritoneal dialysis. Compared with ESA biosimilars, epoetin α did not statistically differ for any of the ten measured outcomes. The quality of evidence varied from low to very low. In the comparison between epoetin α vs. darbepoetin α, no differences were observed for all outcomes, but blood transfusions showed favorable results for darbepoetin α: RR 2.18 (1.31-3.62). The quality of evidence varied from low to very low. No differences were observed between epoetin β and methoxy polyethylene glycol-epoetin β, and between darbepoetin α and methoxy polyethylene glycol-epoetin β, the quality of evidence varied from moderate to very low.
Data from 31 included studies allowed to pool data in meta-analysis related to four different comparisons and eleven outcome measures. Nevertheless, only one result was statistically significant in favor of darbepoetin α in the comparison with epoetin α concerning blood transfusions. For all the other outcomes and comparisons, we did not find any differences in terms of efficacy and security between the EPO considered. The quality of evidence is quite low, and further research could change these results. Further high quality studies examining the comparative effectiveness of ESAs need to be conducted.
有几种促红细胞生成素刺激剂（ESA）可用于治疗慢性肾脏病（CKD）患者的贫血。关于这些治疗选择的可比性的问题不仅仅是一个监管或经济问题。在这些患者中，适当使用原研药或生物类似药需要临床数据的支持。关于预防输血、减轻疲劳、呼吸困难和死亡率或心血管事件，这些药物的比较疗效和安全性数据综述缺乏。
我们对 CENTRAL、PubMed 和 Embase 进行了系统的文献检索，检索时间截至 2015 年 11 月 11 日。我们的纳入标准包括评估不同 ESA 原研药和/或生物类似药比较疗效的随机对照临床试验。考虑的参与者为年龄在 18 岁或以上、因 CKD 导致贫血的成年人。使用 GRADE 系统评估总体证据质量。
我们确定了 30 项符合条件的研究，包括 7843 例 CKD 患者，其中 21/30 项研究包括接受血液透析或腹膜透析的患者。与 ESA 生物类似药相比，促红素 α在十种测量结果中没有统计学差异。证据质量从低到极低不等。在促红素 α与达贝泊汀 α的比较中，所有结果均无差异，但达贝泊汀 α对输血显示出有利的结果：RR 2.18（1.31-3.62）。证据质量从低到极低不等。促红素 β与甲氧基聚乙二醇-促红素 β之间以及达贝泊汀 α与甲氧基聚乙二醇-促红素 β之间无差异，证据质量从中等到极低不等。
31 项纳入研究的数据允许对与四种不同比较和十一种结果测量相关的数据进行荟萃分析。然而，在与促红素 α的比较中，只有一项结果在达贝泊汀 α与输血方面具有统计学意义。对于所有其他结果和比较，我们没有发现 EPO 之间在疗效和安全性方面有任何差异。证据质量相当低，进一步的研究可能会改变这些结果。需要进一步开展高质量的研究，以评估 ESAs 的比较有效性。
