Clinical implications of converting stable haemodialysis patients from subcutaneous to intravenous administration of darbepoetin alfa.

Background: The erythropoiesis-stimulating protein darbepoetin alfa (Aranesp) can be given intravenously (i.v.) or subcutaneously (s.c.). Despite a s.c. bioavailability of only 37%, darbepoetin alfa i.v. or s.c. dose requirements were comparable in previous studies designed to evaluate other aspects of anaemia treatment. The present study was designed to compare i.v. vs s.c. dose requirements.

Methods: A single-centre open-label, prospective and randomized crossover study was undertaken in 71 stable haemodialysis patients. After a run-in period randomized to a 20 week study treatment with either s.c. or i.v. darbepoetin alfa, the patients were crossed over to the other treatment modality for another 20 week study period. The unit dose of weekly darbepoetin alfa was adjusted to maintain each patient's haemoglobin within a target range of -0.8 to +0.8 mmol/l of the individual baseline haemoglobin and between 6.8 and 8.5 mmol/l throughout the study period. The primary endpoint was the mean dose of darbepoetin alfa necessary to maintain the haemoglobin level in the defined range.

Results: Data from 58 patients were available for analysis. Haemoglobin concentrations were maintained effectively in subjects, regardless of whether they received darbepoetin alfa i.v. or s.c.. The overall mean difference in haemoglobin levels during s.c. or i.v. was 0.052 mmol/l (95% confidence interval: -0.132 to 0.236 mmol/l). The difference had no statistical or clinical significance. The population mean darbepoetin alfa dose during i.v. treatment was 32.1 microg/week, compared with a mean value for s.c. treatment of 34.1 microg/week. A paired two-tailed ratio t-test showed that P = 0.036, indicating a 95% probability of a mean dose reduction between 1.2% and 28% by i.v. treatment instead of s.c..

Conclusions: Renal anaemia of stable haemodialysis patients can be treated with darbepoetin alfa more effectively by the i.v. as compared with the s.c. route.