title: Changes in erythropoiesis-stimulating agent (ESA) dosing and haemoglobin levels in US non-dialysis chronic kidney disease patients between 2005 and 2009.
abstract: BACKGROUND
  Recent clinical trials in cancer patients treated with erythropoiesis-stimulating agents (ESAs) and in CKD patients treated to haemoglobin (Hb) targets above the labeled range of 10-12 g/dL with ESAs raised safety concerns regarding ESA therapy. Subsequently, product labeling was revised including addition of a black-box warning and removal of many quality of life claims not supported by current standards, and there were changes in reimbursement and anaemia guidelines. The extent to which these events influenced ESA dosing and Hb levels in patients with chronic kidney disease not on dialysis (CKD-NOD) is not known.
  
  
  METHODS
  We used data collected in a series of cross-sectional surveys between March 2005 and July 2009. Patients with CKD-NOD were selected from a random sample of free-standing US nephrology clinics. Information on demographics, insurance information, laboratory data and ESA use was abstracted from medical records by site investigators. We evaluated ESA treatment (use and dosing) and Hb levels over time and used multivariate linear regression to assess changes in ESA doses and Hb levels over time adjusting for case-mix differences.
  
  
  RESULTS
  Between 2005 and 2009, 15 836 CKD-NOD patients were sampled. During this period, ESA use declined from 60 to 46%, and the mean dose declined from 176 to 136 mcg/month; the largest decline in use and in dose occurred beginning in 2007. Simultaneously, the mean (standard deviation) Hb level in ESA-treated patients declined from 11.5 (1.4) to 10.6 (1.2) g/dL, though the decline was most pronounced starting in 2007. As the mean Hb declined, the percent of treated patients with an Hb > 12 g/dL dropped from 27 to 12%, and the mean dose in this sub-population declined from 173 to 111 mcg/month.
  
  
  CONCLUSIONS
  The emergence of safety concerns and the subsequent changes in product labeling, reimbursement and clinical practice guidelines all appear to have influenced physician dosing practices resulting in less frequent use of ESAs, lower ESA doses and lower achieved Hb levels in CKD-NOD patients.
authors.affiliation: Department of Biostatistics & Epidemiology, Amgen, Inc, Thousand Oaks, CA 91320, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Regidor
authors.forename: William M
authors.initials: WM
authors.lastname: McClellan
authors.forename: Reshma
authors.initials: R
authors.lastname: Kewalramani
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
authors.forename: Brian D
authors.initials: BD
authors.lastname: Bradbury
mesh_terms: D000368:Aged; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006397:Hematinics / Q000008:administration & dosage*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D006397:Hematinics; D006454:Hemoglobins