Twice‐Monthly Administration of a Lower Dose of Epoetin Beta Pegol Can Maintain Adequate Hemoglobin Levels in Hemodialysis Patients

Abstract

Epoetin beta pegol is a continuous erythropoietin receptor activator (CERA) with a long half-life. Although CERA has been shown to maintain adequate hemoglobin (Hb) levels at prolonged dosing intervals, the optimal dosing schedule remains unclear. We therefore compared the efficacy of maintaining hemoglobin levels with administration of twice-monthly CERA (TWICE) versus once-monthly CERA (ONCE). Twenty hemodialysis patients receiving epoetin beta (EPO) were enrolled in this crossover study. Patients were assigned to either the TWICE or the ONCE group based on matching Hb levels and EPO doses. After 6 months of treatment, the CERA dosage was interchanged between the groups and the study was continued for an additional 6 months. The effect of the different regimens on iron metabolism was also assessed during the first 6 months of the study. Hb levels significantly increased in the TWICE group, allowing for a reduction in CERA dosage, while the dose of CERA required to maintain Hb levels in the ONCE group remained unchanged. After the interchange, a decrease in Hb levels with incremental increase in CERA dosage was observed in the TWICE→ONCE group, with the opposite effect observed in the ONCE→TWICE group. Although increases in ferritin and hepcidin-25 levels in the ONCE group were noted at one month, they disappeared at 6 months. Although Hb levels were maintained in both the ONCE and TWICE groups, a twice-monthly administration was advantageous, as it required a lower dose of CERA.

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

“… 13 , 22 CERAs were previously reported to suppress hepcidin levels, inducing the release of stored iron and effective erythropoiesis. 11 , 12 , 14 Unexpectedly, the changes in hepcidin levels did not differ between the QW and Q2W groups in the present study. Similarly, ferritin and TSAT levels did not change in the QW group.…”

“…Hepcidin regulates plasma iron levels by decreasing iron absorption and the release of recycled Hb iron and increasing intracellular iron stores 13,22 . CERAs were previously reported to suppress hepcidin levels, inducing the release of stored iron and effective erythropoiesis 11,12,14 . Unexpectedly, the changes in hepcidin levels did not differ between the QW and Q2W groups in the present study.…”

“…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.…”

Iron Status and Inflammation in Early Stages of Chronic Kidney Disease

“…We also exclude other possible causes of anemia -deficiency of vitamin B12 or folic acid. We did not also assess erythropoietin levels and their relations to iron status as it was reported that hepcidin or prohepcidin were unaffected during therapy with erythropoiesis stimulating agents [36,37]. It appears that some novel biomarkers i.e.…”

Long-term maintenance of hemoglobin levels in hemodialysis patients treated with bi-weekly epoetin beta pegol switched from darbepoetin alfa: a single-center, 12-month observational study in Japan

“…administration [6], enabling reduction of CERA dose [7,8], improving iron use efficiency [7,9,10], and increasing erythropoiesis [6]. The guidelines on the management of renal anemia, published by the Japanese Society for Dialysis Therapy (JSDT) as the 2015 edition, suggest that CERA Q2W may be more effective than Q4W [11].…”