Locatelli Francesco, Villa Giuseppe, Messa Piergiorgio, Filippini Armando, Cannella Giuseppe, De Ferrari Giacomo, Naso Agostino, Rossi Egidio, Formica Marco, Lombardi Luigi, Rotolo Ugo, Conte Feruccio
Division of Nephrology and Dialysis, A. Manzoni Hospital, Via Dell'Eremo 9, Lecco, Italy.
J Nephrol. 2008 May-Jun;21(3):412-20.
Although an erythropoiesis-stimulating agent (ESA) is most frequently administered intravenously for treatment of anemia in patients with chronic kidney disease who are on dialysis, few studies have compared the efficacy of different intravenous (i.v.) dosing schedules.
This multicenter, phase IIIb, open-label, controlled study randomized 289 stable hemodialysis patients to continue with conventional dosing of i.v. epoetin alfa or darbepoetin, or to switch to once-weekly i.v. epoetin alfa at the same cumulative weekly starting dose, to maintain hemoglobin levels at 11.0-13.0 g/dL, and within 1.0 g/dL of the baseline value. Hemoglobin levels and ESA doses were recorded every 4 weeks for 28 weeks.
Hemoglobin levels fell significantly and ESA doses increased significantly between baseline and week 28 (mean of week 16-28 values) in the once-weekly epoetin alfa group, compared with the conventional treatment group (p< 0.001). The adjusted difference in mean hemoglobin levels between the groups was 0.73 g/dL (greater than the threshold for therapeutic equivalence of 0.5 g/dL). The changes between groups from baseline was significant at all time points for hemoglobin levels (0.36, 0.46, 0.81, 0.87, 0.78, 0.62 and 0.49 g/dL) and from week 12 for ESA dose (718.5, 1,326.5, 1,732.0, 1,839.7 and 1,959.1 IU/week; p=0.005). Hemoglobin was maintained at the target level in 78% and 84% of patients on conventional dosing, and 67% and 64% of those on once-weekly epoetin alfa in the intention-to-treat (p=0.1) and per protocol (p=0.016) populations, respectively.
This study did not show therapeutic equivalence of once-weekly i.v. epoetin alfa with conventional dosing regimens.
虽然促红细胞生成素（ESA）最常用于静脉注射，以治疗接受透析的慢性肾病患者的贫血，但很少有研究比较不同静脉给药方案的疗效。
这项多中心、IIIb期、开放标签、对照研究将289名稳定的血液透析患者随机分组，继续接受静脉注射促红细胞生成素α或达比泊汀的常规给药，或在相同的每周累积起始剂量下改用每周一次的静脉注射促红细胞生成素α，以将血红蛋白水平维持在11.0 - 13.0 g/dL，且在基线值的1.0 g/dL范围内。每4周记录一次血红蛋白水平和ESA剂量，共记录28周。
与常规治疗组相比，每周一次促红细胞生成素α组在基线至第28周（第16 - 28周平均值）期间血红蛋白水平显著下降，ESA剂量显著增加（p < 0.001）。两组之间平均血红蛋白水平的调整差异为0.73 g/dL（大于治疗等效性阈值0.5 g/dL）。在所有时间点，两组之间血红蛋白水平从基线的变化均显著（0.36、0.46、0.81、0.87、0.78、0.62和0.49 g/dL），从第12周起ESA剂量的变化也显著（718.5、1326.5、1732.0、1839.7和1959.1 IU/周；p = 0.005）。在意向性治疗人群（p = 0.1）和符合方案人群（p = 0.016）中，分别有78%和84%接受常规给药的患者以及67%和64%接受每周一次促红细胞生成素α给药的患者的血红蛋白维持在目标水平。
本研究未显示每周一次静脉注射促红细胞生成素α与常规给药方案具有治疗等效性。
