title: Intravenous methoxy polyethylene glycol-epoetin beta for haemoglobin control in patients with chronic kidney disease who are on dialysis: a randomised non-inferiority trial (MAXIMA).
abstract: BACKGROUND
  Conventional treatment with epoetin to manage anaemia in chronic kidney disease needs frequent administrations, changes of dose, and close monitoring of haemoglobin concentrations. We aimed to compare the effectiveness of methoxy polyethylene glycol-epoetin beta, given intravenously at 2-week or 4-week intervals, with epoetin treatment one to three times per week for haemoglobin control in haemodialysis patients.
  
  
  METHODS
  We screened 1115 adult patients from 96 centres who had stable chronic renal anaemia and were on dialysis treatment and intravenous maintenance epoetin. We did an open-label, parallel-group, non-inferiority trial to compare two dosing intervals of methoxy polyethylene glycol-epoetin beta with standard epoetin treatment. We established baseline haemoglobin concentration and eligibility over a 4-week run-in period. 223 patients were randomly assigned to receive methoxy polyethylene glycol-epoetin beta every 2 weeks, and 224 to receive it every 4 weeks. The initial dose was based on the average epoetin dose given during the week before the switch. The primary endpoint was change in haemoglobin concentration between baseline and the assessment period. We analysed patients both by intention to treat and per protocol. This study is registered with ClinicalTrials.gov, number NCT00077610.
  
  
  RESULTS
  We excluded 133 of the 673 randomised patients from the per-protocol analysis because they had inadequate iron status or fewer than five haemoglobin measurements during the assessment period or needed red blood cell transfusions. The mean change from baseline haemoglobin for patients who had switched to intravenous methoxy polyethylene glycol-epoetin beta every 2 weeks (-0.71 g/L, 95% CI -2.20 to 0.77) or every 4 weeks (-0.25 g/L, -1.79 to 1.29) was non-inferior to the mean change for patients who continued treatment with epoetin (-0.75 g/L, -2.26 to 0.75) (p<0.0001 for both comparisons). Of the 666 patients who received at least one dose of study drug, the incidence of adverse events or serious adverse events did not differ between groups (p=0.30 and p=0.40, respectively).
  
  
  CONCLUSIONS
  This long-acting erythropoiesis-stimulating agent is as safe as conventional epoetin treatment, and can maintain anaemia management in haemodialysis patients when given intravenously at 4-week dosing intervals.
authors.affiliation: Renal Research Institute, New York, NY 10128, USA. nlevin@rriny.com
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Levin
authors.forename: Steven
authors.initials: S
authors.lastname: Fishbane
authors.forename: Francisco Valdés
authors.initials: FV
authors.lastname: Cañedo
authors.forename: Steven
authors.initials: S
authors.lastname: Zeig
authors.forename: George M
authors.initials: GM
authors.lastname: Nassar
authors.forename: John E
authors.initials: JE
authors.lastname: Moran
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Villa
authors.forename: Ulrich
authors.initials: U
authors.lastname: Beyer
authors.forename: Delphine
authors.initials: D
authors.lastname: Oguey
mesh_terms: D000740:Anemia / Q000188:drug therapy / Q000209:etiology; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006454:Hemoglobins / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000628:therapy; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000009:adverse effects*; D012997:Solvents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D006454:Hemoglobins; D011994:Recombinant Proteins; D012997:Solvents; C103998:epoetin beta; D004921:Erythropoietin; D011092:Polyethylene Glycols