摘要目的 观察每4周1次皮下注射持续性促红细胞生成素受体激活剂(C.E.R.A.)维持慢性肾脏病(CKD)透析贫血患者Hb水平的疗效和安全性.方法 采用开放、随机、对照、多中心临床试验方法.选择血液透析或腹膜透析且已接受促红细胞生成素(EPO)治疗的CKD贫血成年患者,在6周的预治疗期接受EPO-β3每周1～3次皮下注射,维持Hb于100～120 g/L.其后符合入选标准的患者以2∶1比例随机接受C.E.R.A.每4周1次皮下注射(C.E.R.A.组,187例)或EPO-β每周1～3次皮下注射(EPO组,94例)持续治疗28周(包括20周剂量滴定期和8周疗效评估期).C.E.R.A.的起始剂量根据首次给药前1周内使用的EPO-β剂量换算而定.主要研究终点为疗效评估期Hb值相对基线水平的变化.结果 共253例患者完成了28周的治疗.C.E.R.A.组在疗效评估期Hb值相对基线的变化为+2.57 g/L,EPO组为+1.23 g/L,两组差异为1.34 g/L(95％CI-1.11 ～3.78 g/L),其95％ CI的下限大于预设的非劣效性界值-7.5 g/L(P＜0.0001),故认为C.E.R.A.每4周1次皮下注射对CKD透析贫血患者维持Hb水平的疗效非劣于EPO-β.C.E.R.A.组和EPO组平均Hb值维持于目标值的患者比例相当(69.0％比68.9％).C.E.R A.组和EPO组不良事件的总发生率相似(41.7％比46.2％),安全性结果与研究人群的基础疾病有关.结论 在已接受EPO治疗的CKD透析贫血患者中,换用C.E.R.A.每4周1次皮下注射可有效维持Hb水平,且非劣效于EPO-β治疗.CKD透析贫血患者对于皮下注射C.E.R.A.总体上耐受良好.

abstractsObjective To evaluate the efficacy and safety of continuous erythropoietin receptor activator (C.E.R.A.) once every 4 weeks by subcutaneous administration on hemoglobin (Hb)maintenance in dialytic patients with chronic renal anemia who had been treated with stable dose of erythropoietin (EPO).Methods This was an open,randomized,controlled,multi-center trial.All the hemodialysis or peritoneal dialytic patients in EPO maintenance treatment received subcutaneous EPO-β during the 6-week pre-treatment period to maintain Hb level between 100 g/L and 120 g/L.Eligible patients were randomized (2∶1 ) to accept either C.E.R.A.once every 4 weeks by subcutaneous administration ( C.E.R.A.group,n =187 ) or subcutaneous EPO-β 1-3 times weekly ( EPO group,n =94) for 28 weeks (including 20-week dose titration period and 8-week efficacy evaluation period ). The starting dose of C.E.R.A.was converted according to the dose of EPO-β administered in the week preceding the first study drug administration.The primary outcome was the change of Hb level between the baseline and that in the efficacy evaluation period.Results Totally 253 patients completed the whole 28-week treatment.The change of baseline-adjusted mean Hb was +2.57 g/L for C.E.R.A.group and + 1.23 g/L for EPO group,resulting in a treatment difference of 1.34 g/L (95％ CI - 1.11-3.78 g/L).Since the lower limit of 95％ CI was greater than the pre-defined non-inferiority margin -7.5 g/L( P ＜ 0.0001 ),C.E.R.A.once every 4 weeks by subcutaneous administration was clinically non-inferior to EPO regarding the maintenance of stable Hb level.The proportion of patients maintaining Hb level within the range of 100-120 g/L through efficacy evaluation period was similar between the two groups ( 69.0％ for C.E.R.A.group vs 68.9％ for EPO group,P ＞0.05 ).The overall incidence of adverse events was similar between the C.E.R.A.(41.7％)and EPO (46.2％ ) groups ( P ＞ 0.05 ).The safety findings were in accordance with the patients' primary diseases rather than the administration.Conclusions Conversion from EPO to C.E.R.A.once every 4 weeks by subcutaneous injection could maintain the Hb in target level in dialytic patients with renal anemia,and it was non-inferior to EPO.In general,subcutaneous administration of C.E.R.A.is well tolerated in dialytic patients with chronic renal anemia.