Efficacy,safety and tolerance of continuous erythropoietin receptor activator intravenous administration on anemia correction in dialysis patientswith chronic renal anemia

Objective To evaluate the efficacy, safety and tolerance of continuous erythropoietin receptor activator (CERA) once every 2 weeks intravenous injection on anemia correction in dialysis patients compared to Epoetin?β (EPO?β) administration. Methods An open?label, randomized, parallel, active?control and multi?center clinical trial was performed. All the hemodialysis or peritoneal dialysis patients with chronic renal anemia who had not been treated with erythropoiesis?stimulating agents (ESAs) for at least 8 weeks before entering the treatment phase were randomized (1∶1) to receive either CERA once every 2 weeks intravenous administration (CERA group, n=132) or intravenous EPO?β three times weekly (EPO group, n=133) for 24 weeks including 16?week correction period and 8?week efficacy evaluation period. At week 25, the patients who reached the target Hb (defined as Hb≥110 g/L and increase in Hb≥10 g/L from baseline without red blood cell transfusion during the 24 weeks after the first dose) were kept on CERA or EPO?β treatment regimen for the subsequent 28 weeks to evaluate the long?term safety and tolerability. The starting dose of CERA was 0.4 μg/kg. Two primary endpoints were (1) the Hb response rate during the first 24 weeks; and (2)the mean change in Hb between the baseline and the evaluation periods (week 17 to week 24). Results Totally 232 patients (87.5%) completed the first 24?week treatment and 198 patients (74.7%) completed the whole study treatment (52 weeks). The response rate in CERA group during the first 24 weeks was 87.12%95% CI（80.2% to 92.3%）]. Since the lower limit of the 95%CI was greater than 60% (P＜0.01), CERA once every 2 weeks intravenous administration was considered as effective in correction of renal anemia. The difference between CERA group and EPO group in mean change of Hb from evaluation periods to baseline in the per?protocol (PP) population was -4.7 g/L 95%CI (-7.38 g/L to -1.92 g/L)]. Since the lower limit of 95%CI was greater than the pre?defined non?inferiority margin -7.5 g/L (P=0.0205), CERA was considered as non?inferior to EPO in the maintenance of Hb after anemia correction. The Hb level remained stable during the subsequent 28?week extension period in both CERA and EPO groups. During the whole study period, the overall safety findings were similar in CERA and EPO groups, 50.0% and 54.6% of patients experienced at least one adverse event (AE) respectively. The findings from AEs were in accordance with the characteristics of the studied population. Conclusions Intravenous CERA once every 2 weeks is safe and effective for correcting anemia in dialysis patients. Treatment with CERA once every 2 weeks is also non?inferior to 3 times weekly EPO in maintaining the Hb level after the correction. In general, long?term intravenous administration of CERA is well tolerated by dialysis patients with chronic renal anemia.