Casadevall Nicole, Dobronravov Vladimir, Eckardt Kai-Uwe, Ertürk Sehsuvar, Martynyuk Liliya, Schmitt Susanne, Schaffar Gregor, Rudy Anita, Krendyukov Andriy, Ode Marité
Clin Nephrol. 2017 Oct;88(10):190-197. doi: 10.5414/CN109159.
To assess the safety and immunogenicity of subcutaneous (SC) HX575 (epoetin-α) in dialysis- and nondialysis-dependent adult patients with chronic kidney disease (CKD).
Open-label, single-arm, multicenter study in patients (n = 416) from Germany, Italy, Poland, Romania, Russia, Turkey, and Ukraine.
Mean (standard deviation (SD)) age was 52.3 (15.8) years, all patients were Caucasian, and similar proportions were male/female. 250 patients (60.1%) were erythropoiesis-stimulating agent (ESA)-naïve, and 166 (39.9%) were receiving ESA maintenance therapy at study start; mean (SD) on-study treatment duration with HX575 was 43.4 (15.8) weeks and 45.3 (13.7) weeks, respectively. Binding antierythropoietin (EPO) antibodies were detected by radioimmunoprecipitation (RIP) assay in 7 patients (1.7%; incidence 0.019); 5 of these were ESA-naïve at study entry. No patient developed neutralizing antibodies as determined in a cell-based epoetin neutralizing assay. Of the 7 patients with a positive binding anti-EPO RIP assay, 4 tested negative at later time points while continuing HX575 treatment. Three patients had low titers of anti-EPO antibodies at the last study assessment. There were no clinical signs of immunogenicity or hypersensitivity.
CONCLUSIONS: SC HX575 was effective for correcting and maintaining correction of anemia, and the mean weekly dose remained stable over time. .
评估皮下注射 HX575（促红细胞生成素-α）在依赖透析和不依赖透析的成年慢性肾脏病（CKD）患者中的安全性和免疫原性。
对来自德国、意大利、波兰、罗马尼亚、俄罗斯、土耳其和乌克兰的患者（n = 416）进行开放标签、单臂、多中心研究。
平均（标准差）年龄为52.3（15.8）岁，所有患者均为白种人，男女比例相似。250例患者（60.1%）既往未使用过促红细胞生成素刺激剂（ESA），166例患者（39.9%）在研究开始时接受ESA维持治疗；使用HX575的平均（标准差）研究治疗持续时间分别为43.4（15.8）周和45.3（13.7）周。通过放射免疫沉淀（RIP）测定法在7例患者（1.7%；发生率0.019）中检测到结合抗促红细胞生成素（EPO）抗体；其中5例在研究入组时未使用ESA。在基于细胞的促红细胞生成素中和试验中，没有患者产生中和抗体。在7例抗EPO RIP测定呈阳性的患者中，4例在继续使用HX575治疗的后期时间点检测为阴性。3例患者在最后一次研究评估时抗EPO抗体滴度较低。没有免疫原性或超敏反应的临床体征。
皮下注射HX575对纠正和维持贫血的纠正有效，且平均每周剂量随时间保持稳定。
