title: Treatment of anaemia in dialysis patients with unit dosing of darbepoetin alfa at a reduced dose frequency relative to recombinant human erythropoietin (rHuEpo).
abstract: BACKGROUND
  Darbepoetin alfa is an erythropoietic agent with a 3-fold longer elimination half-life than recombinant human erythropoietin (rHuEpo), which allows less frequent dosing. This study investigated the safety and efficacy of darbepoetin alfa for treating anaemia in dialysis patients, using a dosing regimen that was independent of the patient's body weight (unit dosing).
  
  
  METHODS
  Dialysis patients (n=341) maintained on rHuEpo treatment (alfa or beta) were switched to darbepoetin alfa at a reduced dosing frequency, but by the same route of administration [intravenous (i.v.) or subcutaneous (s.c.)]. Patients receiving rHuEpo two or three times weekly changed to once-weekly darbepoetin alfa, and those receiving rHuEpo once weekly changed to once every other week darbepoetin alfa. The unit doses of darbepoetin alfa (10-150 microg) were titrated to maintain haemoglobin concentrations within -1.0 and +1.5 g/dl of the individual mean baseline haemoglobin and between 10 and 13 g/dl for 24 weeks.
  
  
  RESULTS
  Mean change in haemoglobin from baseline to the evaluation period (weeks 21-24) was 0.13 g/dl (95% CI, 0.01, 0.25), which was not clinically relevant. An analysis by route of administration revealed that mean haemoglobin concentrations had increased by 0.58 g/dl (95% CI, 0.33, 0.82) in patients receiving i.v. darbepoetin alfa, and previously treated with i.v. rHuEpo, while remaining unchanged in s.c. patients (0.00 g/dl; 95% CI, -0.13, 0.13) previously treated by s.c. rHuEpo. In addition, there was a statistically significant decrease in mean weekly i.v. darbepoetin alfa dose requirements from 25.2 microg/week at baseline to 21.5 microg/week (P=0.004) during the evaluation period (-17.3%). Subcutaneous weekly dosage requirements increased slightly during the study period (20.8 to 22.7 microg/week; P=0.014). An i.v./s.c. dose ratio of 0.95 (95% CI, 0.78, 1.14) at evaluation confirms previous findings that dose requirements by the i.v. and s.c. routes were not different in patients treated with darbepoetin alfa. Haemoglobin concentrations were also effectively maintained in patients who received darbepoetin alfa once weekly and once every other week. Darbepoetin alfa was well tolerated.
  
  
  CONCLUSIONS
  The treatment of renal anaemia in dialysis patients with unit doses of darbepoetin alfa effectively and safely maintains target haemoglobin concentrations with less frequent dosing. Dose requirements for darbepoetin alfa following i.v. and s.c. administration were not different. The results of this study demonstrate that darbepoetin alfa administered i.v. once weekly, or once every other week is an effective treatment regimen for haemodialysis patients with renal anaemia.
authors.affiliation: Department of Nephrology and Dialysis, A. Manzoni Hospital, Via Dell'Eremo 9/11, 23900 Lecco, Italy. nefrologia@ospedale.lecco.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Bernard
authors.initials: B
authors.lastname: Canaud
authors.forename: Francis
authors.initials: F
authors.lastname: Giacardy
authors.forename: Alejandro
authors.initials: A
authors.lastname: Martin-Malo
authors.forename: Nigel
authors.initials: N
authors.lastname: Baker
authors.forename: Janet
authors.initials: J
authors.lastname: Wilson
mesh_terms: D000368:Aged; D000740:Anemia / Q000097:blood / Q000209:etiology*; D000068256:Darbepoetin alfa; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000009:adverse effects*; D019233:Retreatment; D012449:Safety
chemical_list: D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa