C.E.R.A.的安全性概况：慢性肾脏病患者的汇总分析

C.E.R.A. safety profile: a pooled analysis in patients with chronic kidney disease.

作者信息

Locatelli F, Mann J F E, Aldigier J C, Sanz Guajardo D, Schmidt R, Van Vlem B, Sulowicz W, Dougherty F C, Beyer U

机构信息

Department of Nephrology and Dialysis and renal Transplant, A. Manzoni Hospital, Lecco Italy.

出版信息

Clin Nephrol. 2010 Feb;73(2):94-103. doi: 10.5414/cnp73094.

DOI:10.5414/cnp73094

PMID:20129016

Abstract

BACKGROUND

C.E.R.A., a continuous erythropoietin receptor activator, is a long-acting erythropoiesis-stimulating agent (ESA) that is approved for the treatment of renal anemia. This analysis evaluated the safety profile of C.E.R.A. in comparison to that of other ESAs in patients with chronic kidney disease (CKD).

METHODS

Safety parameters were analyzed in a pooled population comprising all patients with CKD on dialysis and not on dialysis from the completed Phase II and Phase III studies in the C.E.R.A. clinical program (Phase II/III population); patients were treated with either C.E.R.A. (n = 1,789) or comparator ESA (n = 948). Differences between treatment groups in safety parameters were identified by either a 2% difference in incidence between groups, or a statistically significant difference between groups (p < or = 0.05 with the Fisher's exact test, which was used as a conservative screening tool). To assess changes in safety findings over time, long-term safety data were analyzed from patients who were given the option to enter long-term safety studies upon completing their initial Phase II/III study (safety extension population).

RESULTS

Compared with the C.E.R.A. group, the incidence of adverse events (AEs) was higher in the comparator ESA group in the Phase II/III population (C.E.R.A. vs. comparator ESA, 89.5% vs. 91.8%, p = 0.067), and significantly so in the safety extension population (93.0% vs. 95.8%, p = 0.003). The incidence of serious AEs was significantly higher in the comparator ESA group than in the C.E.R.A. group in both analysis populations (Phase II/III population, 37.8% vs. 42.4%, p = 0.021; safety extension population, 53.3% vs. 59.7%, p = 0.001). However, there was no consistent pattern of clinical events that could explain these differences between the treatment groups.

CONCLUSION

Analysis of safety events in patients with renal anemia receiving long-term treatment with C.E.R.A. shows a safety profile comparable to that of other ESAs.

摘要

背景

C.E.R.A.是一种持续促红细胞生成素受体激活剂，是一种长效促红细胞生成刺激剂（ESA），已被批准用于治疗肾性贫血。本分析评估了C.E.R.A.与其他ESA相比在慢性肾脏病（CKD）患者中的安全性。

方法

在C.E.R.A.临床项目中完成的II期和III期研究中，对所有接受透析和未接受透析的CKD患者组成的汇总人群进行安全性参数分析（II/III期人群）；患者接受C.E.R.A.治疗（n = 1789）或对照ESA治疗（n = 948）。治疗组之间安全性参数的差异通过组间发生率2%的差异或组间统计学显著差异来确定（Fisher精确检验p≤0.05，用作保守筛查工具）。为了评估安全性结果随时间的变化，对完成初始II/III期研究后可选择进入长期安全性研究的患者的长期安全性数据进行了分析（安全性扩展人群）。

结果

与C.E.R.A.组相比，II/III期人群中对照ESA组不良事件（AE）的发生率更高（C.E.R.A.组与对照ESA组，89.5%对91.8%，p = 0.067），在安全性扩展人群中差异显著（93.0%对95.8%，p = 0.003）。在两个分析人群中，对照ESA组严重AE的发生率均显著高于C.E.R.A.组（II/III期人群，37.8%对42.4%，p = 0.021；安全性扩展人群，53.3%对59.7%，p = 0.001）。然而，没有一致的临床事件模式可以解释治疗组之间的这些差异。