title: Outcomes in patients with chronic kidney disease not on dialysis receiving extended dosing regimens of darbepoetin alfa: long-term results of the EXTEND observational cohort study.
abstract: Extended dosing of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa (DA) once biweekly or monthly reduces anaemia treatment burden. This observational study assessed outcomes and dosing patterns in patients with chronic kidney disease not on dialysis (CKD-NoD) commencing extended dosing of DA.
  
  
  
  Adult CKD-NoD patients starting extended dosing of DA in Europe or Australia in June 2006 or later were followed up until December 2012. Outcomes included haemoglobin (Hb) concentration, ESA dosing, mortality rates and receipt of dialysis and renal transplantation. Subgroup analyses were conducted for selected outcomes.
  
  
  
  Of 6035 enrolled subjects, 5723 (94.8%) met analysis criteria; 1795 (29.7%) received dialysis and 238 (3.9%) underwent renal transplantation. Mean (standard deviation) Hb concentration at commencement of extended dosing was 11.0 (1.5) g/dL. Mean [95% confidence interval (CI)] Hb 12 months after commencement of extended dosing (primary outcome) was 11.6 g/dL (11.5, 11.6) overall and was similar across countries, with no differences between subjects previously treated with an ESA versus ESA-naïve subjects, subjects with versus without prior renal transplant or diabetics versus non-diabetics. Weekly ESA dose gradually decreased following commencement of extended DA dosing and was similar across subgroups. The decrease in weekly DA dose was accompanied by an increase in the proportion of patients receiving iron therapy. Hb concentrations declined following changes in ESA labels and treatment guidelines. The mortality rate (95% CI) was 7.06 (6.68, 7.46) deaths per 100 years of follow-up. Subjects alive at study end had stable Hb concentrations in the preceding year, while those who died had lower and declining Hb concentrations in their last year.
  
  
  
  Long-term, extended dosing of DA maintained Hb concentrations in patients already treated with an ESA and corrected and maintained Hb in ESA-naïve patients.
authors.affiliation: Klinik für Nephrologie und Dialyseverfahren, Klinikum Lüdenscheid, Lüdenscheid, Germany.
authors.forename: Jan-Christoph
authors.initials: JC
authors.lastname: Galle
authors.affiliation: Amgen Ltd, Cambridge, UK.
authors.forename: Janet
authors.initials: J
authors.lastname: Addison
authors.affiliation: Renal Unit, Liverpool Hospital, Sydney, Australia.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Suranyi
authors.affiliation: Department of Nephrology and Renal Transplantation, University Hospitals Gasthuisberg, Leuven, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Claes
authors.affiliation: Department of Nephrology, Dialysis and Transplantation, Ospedale San Camillo-Forlanini, Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Di Giulio
authors.affiliation: Clinique du Mont-Louis, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Guerin
authors.affiliation: Department of Molecular and Clinical Medicine/Nephrology, Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Herlitz
authors.affiliation: South-Buda Nephrology Centre (Department of Nephrology-Hypertension of St Imre Teaching Hospital and B. Braun Avitum Hungary CPLC 1st Dialysis Centre), Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Kiss
authors.affiliation: Clinical Development, Amgen (Europe) GmbH, Zug, Switzerland.
authors.forename: Mourad
authors.initials: M
authors.lastname: Farouk
authors.affiliation: Biostatistics, Amgen Ltd, Cambridge, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Manamley
authors.affiliation: Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wirnsberger
authors.affiliation: Oxford Kidney Unit, Churchill Hospital, Oxford, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Winearls
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D000068256:Darbepoetin alfa / Q000008:administration & dosage*; D005260:Female; D006397:Hematinics / Q000008:administration & dosage*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D006397:Hematinics; D000068256:Darbepoetin alfa
keywords: anaemia; chronic kidney disease; darbepoetin alfa; erythropoiesis-stimulating agent; extended dosing