Correction of anaemia with darbepoetin alfa in patients with chronic kidney disease receiving dialysis.

Abstract

Darbepoetin alfa is a new recombinant erythropoietic protein with a 3-fold longer half-life than recombinant human erythropoietin (rHuEpo). The optimal starting dose and frequency of administration of darbepoetin alfa were investigated for treating renal anaemia in dialysis patients. Two multicentre, sequential dose-escalation studies examined the i.v. route of administration of darbepoetin alfa in haemodialysis patients (n=75) and the s.c. route in peritoneal dialysis patients (n=47). Patients were randomized to receive darbepoetin alfa at doses ranging from 0.075 to 0.75 microg/kg/week administered as either a once weekly or a three-times weekly injection. Patients achieving the primary endpoint of a > or = 1 g/dl increase in haemoglobin after 4 weeks continued darbepoetin alfa for up to 52 weeks. Safety was assessed by adverse event reports, changes in laboratory values and vital signs, and antibody screening. Darbepoetin alfa produced dose-related increases in haemoglobin over the first 4 weeks of treatment in both studies. Two dose levels (0.45 and 0.75 microg/kg/week) increased the haemoglobin by > or = 1 g/dl in 60-80% of patients, and no difference between once weekly and three-times weekly dosing was apparent. For patients who continued treatment up to 52 weeks, haemoglobin was maintained between 10 and 13 g/dl from mean baseline values of 8.4 and 8.7 g/dl. The adverse event profile was similar to that associated with rHuEpo therapy, and no antibodies to darbepoetin alfa were detected. Darbepoetin alfa is safe and effective for the treatment of anaemia in dialysis patients. The optimal weekly starting dose is 0.45-0.75 microg/kg and once weekly dosing is possible for both the s.c. and i.v. routes of administration.