University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Drugs Aging. 2009;26(8):665-75. doi: 10.2165/11316450-000000000-00000.
Anaemia is a common complication of chronic kidney disease (CKD) and is associated with increased rates of mortality and diminished quality of life in patients with CKD. Although extended dosing with darbepoetin alfa, an erythropoiesis-stimulating agent (ESA), has been shown to be effective in maintaining haemoglobin (Hb) levels in CKD patients, little information is published on the use of darbepoetin alfa in the correction and maintenance of Hb levels in elderly CKD patients naive to ESA therapy.
This post hoc subanalysis of data from two clinical trials was conducted to investigate the efficacy and safety profile of de novo every-other-week (q2w) darbepoetin alfa in elderly patients with CKD-associated anaemia (not on dialysis), as compared with that of a younger (aged <65 years) patient cohort.
This analysis was based on data obtained from two open-label, single-arm, multicentre studies of similar design. Patients were aged >or=18 years and naive to previous ESA therapy. Darbepoetin alfa administration was initiated at 0.75 microg/kg and titrated according to individual patient requirements to achieve and maintain Hb levels between 11.0 and 13.0 g/dL. The proportion of patients who achieved the primary endpoint, Hb >or=11.0 g/dL (study 1), and an Hb level between 11.0 and 13.0 g/dL (study 2) at weeks 4, 8 and 12 weeks and at the end of the study were determined. The results of this subanalysis were stratified by age (<65, 65-74 and >or=75 years).
A total of 203 patients were enrolled in the two studies; 60% were female, 84 (41%) were aged <65 years, 57 (28%) were aged 65-74 years and 62 (31%) were aged >or=75 years. The proportion of patients who achieved Hb levels of >or=11.0 g/dL in study 1 and 11.0-13.0 g/dL in study 2 at week 20 were 93%, 96% and 92%, respectively, for the three age groups. Weight-adjusted q2w darbepoetin alfa doses were similar between the age groups and stable throughout the study period. The mean (standard deviation) Hb levels at week 21 were 12.0 (1.2), 12.7 (1.1) and 12.6 (1.0) g/dL in subjects aged <65, 65-74 and >or=75 years, respectively. The median (standard error) time to reach the primary endpoint was 5.0 (4.7), 5.0 (5.7) and 5.0 (5.7) weeks for subjects aged <65 years, 65-74 years and >or=75 years, respectively. The safety profiles of q2w darbepoetin alfa in both the older and younger age-groups were consistent with those expected for patients with CKD not receiving dialysis.
The results of this study suggest that ESA-naive subjects aged <65, 65-74 and >or=75 years of age with CKD (not receiving dialysis) who received q2w darbepoetin alfa were able to achieve and maintain Hb levels at 11.0-13.0 g/dL. The de novo q2w treatment regimen with darbepoetin alfa described in the present report may help optimize anaemia management in CKD-associated anaemia patients, including those in the older adult population.
贫血是慢性肾脏病（CKD）的常见并发症，与 CKD 患者的死亡率增加和生活质量下降有关。尽管延长使用促红细胞生成素刺激剂（ESA）达贝泊汀治疗可有效维持 CKD 患者的血红蛋白（Hb）水平，但关于 ESA 治疗初治的老年 CKD 患者使用达贝泊汀纠正和维持 Hb 水平的信息很少。
本研究是对两项临床试验数据的事后亚组分析，旨在研究初治的老年（年龄≥65 岁）CKD 相关贫血（未透析）患者每两周（q2w）一次给予达贝泊汀的疗效和安全性。
该分析基于两项设计相似的开放标签、单臂、多中心研究的数据。患者年龄≥18 岁，且未接受过ESA 治疗。达贝泊汀起始剂量为 0.75μg/kg，并根据患者的个体需求滴定剂量，以达到并维持 11.0-13.0g/dL 的 Hb 水平。主要终点（研究 1）为 Hb≥11.0g/dL，次要终点（研究 2）为 Hb 在 11.0-13.0g/dL，分别确定第 4、8、12 周和研究结束时达到该终点的患者比例。该亚组分析结果按年龄（<65、65-74 和≥75 岁）分层。
共有 203 例患者入组了这两项研究；60%为女性，84 例（41%）年龄<65 岁，57 例（28%）年龄 65-74 岁，62 例（31%）年龄≥75 岁。研究 1 中 Hb 水平≥11.0g/dL 的患者比例和研究 2 中 Hb 水平在 11.0-13.0g/dL 的患者比例，三组年龄组分别为 93%、96%和 92%。三组年龄组的体重校正 q2w 达贝泊汀剂量相似，且整个研究期间保持稳定。<65、65-74 和≥75 岁年龄组患者在第 21 周的平均（标准偏差）Hb 水平分别为 12.0（1.2）、12.7（1.1）和 12.6（1.0）g/dL。<65 岁年龄组达到主要终点的中位（标准误差）时间为 5.0（4.7）周，65-74 岁年龄组和≥75 岁年龄组分别为 5.0（5.7）和 5.0（5.7）周。在接受 q2w 达贝泊汀治疗的老年和年轻年龄组中，ESA 初治患者的安全性与未接受透析的 CKD 患者的预期安全性一致。
本研究结果表明，接受 q2w 达贝泊汀治疗的 ESA 初治、年龄<65、65-74 和≥75 岁、未透析的 CKD 患者能够达到并维持 11.0-13.0g/dL 的 Hb 水平。本报告中描述的 ESA 初治患者 q2w 达贝泊汀治疗方案可能有助于优化 CKD 相关贫血患者的贫血管理，包括老年患者。
