A Randomized Control Study on the Procedure for Switching Epoetin Beta (EPO) to Epoetin Beta Pegol (CERA) in the Treatment of Renal Anemia in Maintenance Hemodialysis Patients

Abstract

Background/Aims: We investigated the method of switching EPO to CERA that does not cause a decrease in the Hb level. Methods: Fifty EPO-treated patients were randomly divided into two groups in which CERA was administered every two weeks (Q2W) or every four weeks (Q4W). After 8 weeks of treatment, the frequency of administration was changed to Q4W in the former. Follow-up was performed for 24 weeks. Results: There was no difference in the Hb level between the two groups until 6 weeks. In the Q2W group, the Hb maintained a stable level throughout a study period. However, in the Q4W group, the Hb level was significantly lower than in the Q2W group at weeks 9, 11, and 13. Conclusion: EPO switching to CERA without a decrease in the Hb level could be achieved by administering CERA every two weeks, but not every four weeks, for a specific period after switching. © 2014 S. Karger AG, Basel

2015 Japanese Society for Dialysis Therapy: Guidelines for Renal Anemia in Chronic Kidney Disease

“…The reasons for this were reported as follows: (1) it takes 6 weeks for the serum CERA level to stabilize, as shown by a Japanese clinical study [96], and (2) it takes approximately 12 weeks for the dose of CERA administered once every 4 weeks to stabilize after switching from rHuEPO [97]. Moreover, Toida et al compared the efficacy of CERA administered once every 2 weeks after switching from rHuEPO with that of CERA administered once every 4 weeks after switching from rHuEPO in a RCT [98]. They reported that the Hb level decreased in patients who were administered CERA once every 4 weeks, while an optimal Hb level was maintained stably in those administered CERA once every 2 weeks.…”

Comparison of the effects of weekly and biweekly intravenous CERA administration on erythropoiesis: A randomized controlled trial

“…Some reports described the superiority of biweekly CERA administration over monthly administration in that biweekly administration could maintain Hb levels using a lower overall CERA dose. 8 , 9 , 10 , 11 It is noteworthy that biweekly CERA administration maintained ferritin and hepcidin, a negative regulator of iron uptake in the small intestine and iron release from macrophages, at lower levels for 4 weeks after administration than monthly administration. 12 , 13 This result suggested that biweekly administration is advantageous for absorption and iron utilization.…”

Influence of continuous erythropoietin receptor activator (CERA) administration intervals on erythropoietic effect in hemodialysis patients

“…Although conversion to CERA with intervals of once every 2 weeks (Q2W) or 4 weeks (Q4W) from other ESAs is achieved safely in hemodialysis patients and oncemonthly administration is recommended in Japan, the optimal interval of CERA administration is not known. Recently, it is reported that more continuous erythropoiesis was achieved with a Q2W administration of CERA than Q4W [7], and Q2W administration of CERA is more effective than Q4W to achieve target hemoglobin (Hb) levels [8]. Although we also reported more effective erythropoiesis of CERA by Q2W than Q4W, the fluctuation of Hb levels during Q4W is greater than that during Q2W [9], which makes it difficult to compare the true effect of the interval of CERA administration on Hb levels.…”

“…Although the precise mechanisms are not clear, in hemodialysis patients, ESA administration exerts a biphasic pattern of serum hepcidin-25 levels; early upregulation followed by late downregulation [14], and low serum hepcidin levels Variables are represented as mean ± standard deviation HD hemodialysis, BUN blood urea nitrogen, Cr creatinine, TP total protein, Alb albumin, Hb hemoglobin, CRP C-reactive protein, Fe iron facilitate iron utilization, which results in a decrease of serum ferritin levels. The degree of iron utilization and recruitment to the hematopoietic system seems to differ according to the type of ESAs [14][15][16] and interval of dosing [7,8]. Transient reduction of serum hepcidin and ferritin levels induced by CERA administration reach a maximum around 1 week after dosing and return to pre-administration levels by 4 weeks, with this being the rationale of the once-monthly administration of CERA.…”

“…These transient changes of serum ferritin and hepcidin levels induced by CERA are considered to be due to sustained stimulation of erythropoiesis by CERA which lasts much longer than that induced by epoetin. Although CERA has a long half-life, and once-monthly administration of CERA is safe and reported to save up to 144 injections per hemodialysis patient per year compared with three times weekly dosing [17], it is reported that Q2W administration of CERA is more effective than Q4W to achieve target Hb levels [7,8,17], which made us wonder what would be the optimal interval of CERA administration from the standpoint of efficacy. As shown in Table 2, our study demonstrated higher mean reticulocyte counts in patients with CERA administered at Q2W than Q4W.…”