Glycoengineering of Interferon-β 1a Improves Its Biophysical and Pharmacokinetic Properties
OBJECTIVE Darbepoetin alfa is an erythropoietic-stimulating protein with a threefold longer half-life than recombinant human erythropoietin (rHuEPO) and can be used less frequently in the treatment of renal anemia. The purpose of this single-center single-arm study was to determine whether darbepoetin alfa, when administered at extended dose intervals, is as effective as rHuEPO for the treatment of renal anemia in patients on peritoneal dialysis. METHODS Patients on peritoneal dialysis for at least 3 years receiving stable rHuEPO therapy were shifted to darbepoetin alfa administered every week, or every other week, using the recommended 200:1 conversion factor. The doses of darbepoetin alfa were titrated to maintain hemoglobin within +/-1.0 g/dL of patients' baseline values and within a range of 9.0 - 12.0 g/dL for up to 24 weeks (20-week dose titration period followed by 4-week evaluation period). The primary end point was the change in hemoglobin levels between baseline and evaluation period. RESULTS 73 patients completed the study; mean age was 52.1 years; 30 males. Mean baseline and evaluation period hemoglobin levels were similar (9.56 +/- 1.11 vs 9.73 +/- 1.41 g/dL, p = 0.248). Mean rHuEPO dose was 92.9 IU/kg/week (equivalent to 0.46 microg/kg/week darbepoetin alfa), which was higher than darbepoetin alfa dose during the evaluation period (0.46 vs 0.34 microg/kg/week, p = 0.038). In addition, ferritin levels decreased (483 +/- 26 vs 396 +/- 19 ng/dL, p = 0.014). The other parameters, such as albumin, C-reactive protein, transferrin saturation, Kt/V, and weekly creatinine clearance showed no statistical difference between the two regimens. No serious or major adverse effects were observed with darbepoetin alfa during the study. CONCLUSIONS Using lower dosage and frequency, darbepoetin alfa effectively maintains hemoglobin levels in peritoneal dialysis patients previously maintained on erythropoietin beta. Similar effects on hemoglobin can be maintained with even lower levels of ferritin during darbepoetin alfa use. These results show that darbepoetin alfa is safe, effective, and convenient in treating renal anemia in peritoneal dialysis patients.