title: Unit dosing of darbepoetin alfa for thetreatment of anemia in patients with end-stage renal disease being switched from recombinant human erythropoietin: Results of a phase IIIb, 27-week, multicenter, open-label study in Greek patients.
abstract: BACKGROUND
  Darbepoetin alfa is an erythropoietis-stimulating glycoprotein with a ∼3-fold longer t1/2 and greater biological activity compared with recombinant human erythropoietin (rHuEPO).
  
  
  OBJECTIVE
  The objective of this study was to evaluate the efficacy andtolerability of long-term (24-week) darbepoetin alfa treatment in maintaining hemoglobin (Hb) concentrations in the target range of 10 to 13 g/dL in patients undergoing dialysis; the patients were switched from rHuEPO to a less-frequent dosing regimen of darbepoetin alfa without an increase in dose.
  
  
  METHODS
  In this Phase IIlb, open-label, multicenter study, patients withend-stage renal disease (ESRD) undergoing dialysis who were receiving rHuEPO BIW or TIW at baseline were switched to darbepoetin alfa QW; patients receiving rHuEPO QW were switched to darbepoetin alfa Q2W Administration of darbepoetin alfa was by the same route as previous rHuEPO administration (IV or SC). Patients received darbepoetin alfa for 24 weeks, including a 20-week drug titration period followed by a 4-week, stable-dose evaluation period. The mode, dose, and frequency of administration of darbepoetin alfa were compared with those of baseline rHuEPO. Tolerability assessment was based on spontaneous reporting and laboratory tests (hematology, vital sign measurement, iron status, and biochemistry).
  
  
  RESULTS
  The study comprised 173 patients who were divided into 2 groups by route of administration (IV group, n = 146; SC group, n = 27). Mean (SE) adjusted increases in Hb concentration from baseline to the evaluation period for patients receiving darbepoetin alfa QW were 0.94 (0.32) g/dL and 0.38 (0.30) g/dL for the IV or SC routes, respectively (P = 0.004 and NS, respectively). For patients receiving darbepoetin alfa Q2W the mean (SE) adjusted increases in Hb concentration were 0.08 (0.53) g/dL and 0.48 (0.35) g/dL for the IV and SC routes, respectively (both, P = NS). No significant differences in IV/SC dose ratio were observed between the 2 routes of administration. In addition, no increases in darbepoetin alfa dose were observed. The most commonly reported adverse events were hypertension (8 patients [5%]) and vascular access thrombosis (4 [2%]). The incidence of treatment-related adverse events was 6 (3%).
  
  
  CONCLUSIONS
  Darbepoetin alfa effectively maintained Hb concentrations within the target range without an increase in dose, even at a reduced dosing frequency. Overall, darbepoetin alfa was well tolerated.
authors.affiliation: Renal Unit, General Prefectorial Hospital of Kalamata, Kalamata, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Bristoyiannis
authors.affiliation: RenalUnit, General District Hospital of Agrini, Agrinio, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Germanos
authors.affiliation: Renal Unit, American-HellenicEducational Progressive Association (AHEPA) University Hospital, Thessaloniki, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Grekas
authors.affiliation: Renal Unit, General Prefectorial Hospital of Xanthi, Xanthi, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Hatzidimitriou
authors.affiliation: Renal Unit, General District Hospital of Nikea, Piraeus, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Iatrou
authors.affiliation: Renal Unit,Ippokratio University Hospital, Thessaloniki, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Memmos
authors.affiliation: Renal Unit, Private Hospital Henry Dunant, Athens, Greece.
authors.forename: Spiros
authors.initials: S
authors.lastname: Moutafis
authors.affiliation: Renal Unit, Venizelio Hospital, Heraklio, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Papachristoforou
authors.affiliation: Renal Unit, Private Clinic lasis, Piraeus, Greece.
authors.forename: Antonis
authors.initials: A
authors.lastname: Papadoniou
authors.affiliation: Renal Unit, Hatzikosta Hospital,Ioannina, Greece.
authors.forename: Michalis
authors.initials: M
authors.lastname: Pappas
authors.affiliation: Renal Unit, Papageorgiou Hospital, Thessaloniki, Greece.
authors.forename: George A
authors.initials: GA
authors.lastname: Sakellariou
authors.affiliation: Department of Internal Medicine, Medical School, University of Ioannina, Ioannina,Greece.
authors.forename: Kostas C
authors.initials: KC
authors.lastname: Siamopoulos
authors.affiliation: Renal Unit, Popanikoloou Hospital, Thessaloniki, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Sombolos
authors.affiliation: Renal Unit, Kyanos Stavros Hospital, Athens, Greece.
authors.forename: Kiriaki
authors.initials: K
authors.lastname: Stamatelou
authors.affiliation: Renal Unit, Laïko Hospital, Athens, Greece.
authors.forename: Charalambos P
authors.initials: CP
authors.lastname: Stathakis
authors.affiliation: Renal Unit, N.I.M.TS. Hospital, Athens, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Stavgiannoudakis
authors.affiliation: Renal Unit, General District University Hospital of Heraklio, Crete, Greece.
authors.forename: Spiros
authors.initials: S
authors.lastname: Stratigis
authors.affiliation: Renal Unit, General Prefectorial Hospital of Volos, Volos, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Syrganis
authors.affiliation: Renal Unit, General PrefectorialHospital of Veria, Veria, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Tsakiris
authors.affiliation: Renal Unit, General Private Hospital Ygeia, Athens, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Valis
authors.affiliation: Renal Unit, University Hospital of Patras, Patras, Greece.
authors.forename: Jannis G
authors.initials: JG
authors.lastname: Vlahojannis
authors.affiliation: Renal Unit, Amalia Fleming Hospital, Athens, Greece.
authors.forename: Dimosthenis
authors.initials: D
authors.lastname: Vlassopoulos
keywords: darbepoetin alfa; dialysis; efficacy; rHuEPO; renal disease; safety; tolerability