Locatelli Francesco, Choukroun Gabriel, Truman Matt, Wiggenhauser Alfons, Fliser Danilo
Nephrology, Dialysis and Transplantation Department, Alessandro Manzoni Hospital, Lecco, Italy.
Nephrology, Dialysis and Transplantation Department, CHU Amiens and University of Picardie Jules Verne, Amiens, France.
Adv Ther. 2016 Apr;33(4):610-25. doi: 10.1007/s12325-016-0309-6. Epub 2016 Mar 10.
Erythropoiesis-stimulating agents and iron are commonly used in patients with chronic kidney disease with the aim of correcting anemia and maintaining stable hemoglobin levels. We analyzed pooled data from 13 studies with similar designs included in the Umbrella Continuous Erythropoietin Receptor Activator (C.E.R.A.) program to investigate the effects of continuous erythropoiesis receptor activator in clinically relevant subgroups of patients with chronic kidney disease and to determine whether the efficacy and safety outcomes demonstrated in the overall chronic kidney disease population are maintained in specific subgroups.
Data from 13 Phase III trials set up with similar design were retrospectively pooled for this analysis. Patients with chronic kidney disease who had previously been receiving epoetin or darbepoetin were switched to continuous erythropoiesis receptor activator once-monthly after a 4- to 8-week screening period. Patients entered a 16-week continuous erythropoiesis receptor activator dose-titration period followed by an 8-week evaluation period. In total, 2060 patients were included in the analysis. Subgroups were defined based on: hemoglobin target range [lower (10.0-12.0 g/dL)/upper (10.5-13.0 g/dL)], gender (female/male), age (<65/≥65), baseline N-terminal pro-B-type natriuretic peptide levels (<5000/≥5000), cardiovascular risk factors (diabetes/cardiac/vascular/none).
Across all subgroups analyzed, switching from shorter-acting erythropoiesis-stimulating agents to continuous erythropoiesis receptor activator once-monthly maintained stable hemoglobin concentrations in a high proportion of patients (78%), with only moderate hemoglobin fluctuations and a low number of dose changes. The safety profile across subgroups was as expected based on pre-existing risk factors; observed increases in adverse events were attributable to underlying risk factors rather than study drug.
This retrospective analysis of 13 trials showed that continuous erythropoiesis receptor activator once-monthly maintained stable hemoglobin levels across a number of clinically relevant patient subgroups, including those with higher inherent cardiovascular risk. The safety profile was consistent with that previously established in the chronic kidney disease population. CLINICALTRIALS.
NCT00413894/NCT00545571/NCT00517413/NCT00560404/NCT00882713/NCT00550680/NCT00576303/NCT00660023/NCT00717821/NCT00642850/NCT00605293/NCT00661505/NCT00699348.
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
促红细胞生成素和铁剂常用于慢性肾脏病患者，目的是纠正贫血并维持稳定的血红蛋白水平。我们分析了伞形持续促红细胞生成素受体激活剂（C.E.R.A.）项目中13项设计相似的研究的汇总数据，以研究持续促红细胞生成素受体激活剂在慢性肾脏病临床相关亚组患者中的作用，并确定在整个慢性肾脏病总体人群中所显示的疗效和安全性结果在特定亚组中是否得以维持。
对13项设计相似的III期试验数据进行回顾性汇总分析。曾接受依泊汀或达贝泊汀治疗的慢性肾脏病患者，在经过4至8周的筛查期后，改为每月一次注射持续促红细胞生成素受体激活剂。患者进入为期16周的持续促红细胞生成素受体激活剂剂量滴定期，随后是8周的评估期。总计2060例患者纳入分析。亚组根据以下因素定义：血红蛋白目标范围[较低（10.0 - 12.0 g/dL）/较高（10.5 - 13.0 g/dL）]、性别（女性/男性）、年龄（<65岁/≥65岁）、基线N末端B型利钠肽原水平（<5000/≥5000）、心血管危险因素（糖尿病/心脏/血管/无）。
在所有分析的亚组中，从短效促红细胞生成素转换为每月一次的持续促红细胞生成素受体激活剂，在很大比例的患者（78%）中维持了稳定的血红蛋白浓度，血红蛋白波动仅为中度，且剂量变化次数较少。基于既往危险因素，各亚组的安全性概况符合预期；观察到的不良事件增加归因于潜在危险因素而非研究药物。
这项对13项试验的回顾性分析表明，每月一次的持续促红细胞生成素受体激活剂在多个临床相关患者亚组中维持了稳定的血红蛋白水平，包括那些固有心血管风险较高的亚组。安全性概况与先前在慢性肾脏病总体人群中确立的一致。临床试验。
NCT00413894/NCT00545571/NCT00517413/NCT00560404/NCT00882713/NCT00550680/NCT00576303/NCT00660023/NCT00717821/NCT00642850/NCT00605293/NCT00661505/NCT00699348。
瑞士巴塞尔的F. Hoffmann-La Roche Ltd公司。
