Switching from Epoetin Alfa (Epogen®) to Epoetin Alfa-Epbx (RetacritTM) Using a Specified Dosing Algorithm: A Randomized, Non-Inferiority Study in Adults on Hemodialysis

Am J Nephrol. 2018;48(3):214-224. doi: 10.1159/000492621. Epub 2018 Sep 7.


Background: For patients with anemia undergoing hemodialysis, erythropoiesis-stimulating agents (ESAs) are typically dosed via precise algorithms. Using one such algorithm, we assessed the maintenance of hemoglobin levels in patients switched from epoetin alfa reference product (Epogen®) to epoetin alfa-epbx (RetacritTM; a biosimilar to US-licensed Epogen®/Procrit®).

Methods: This randomized, open-label, non-inferiority study was conducted at Fresenius Medical Care North America (FMCNA) hemodialysis centers. Patients with anemia and chronic kidney disease undergoing maintenance hemodialysis and receiving routine intravenous (IV) Epogen® were randomized 1: 1 to switch to IV RetacritTM or continue standard-of-care (Epogen®) for 24 weeks, using analogous versions of the FMCNA ESA-dosing algorithm. The primary endpoint was the proportion of time patients' hemoglobin was 9-11 g/dL during weeks 17-24.

Results: Of 432 randomized patients, 418 received treatment (RetacritTM, n = 212; standard-of-care, n = 206) and comprised the full analysis set. A similar proportion of patients discontinued from each arm. The proportion of time patients' hemoglobin was within the target range was 61.9% (95% CI 57.5-66.2) in the RetacritTM arm and 63.3% (95% CI 58.7-67.7) in the standard-of-care arm. The difference in proportions between treatment arms was -1.4% (95% CI -7.6 to 4.9), and the lower bound of the confidence interval was within the pre-specified non-inferiority margin of -12.5%. There was no statistically significant difference between arms in the mean change from baseline in the weekly mean ESA dose during weeks 17-24, and no clinically relevant differences in safety outcomes.

Conclusions: Switching to RetacritTM was non-inferior to continuing -Epogen® in maintaining hemoglobin levels in patients receiving hemodialysis, when both ESAs were dosed using a specified algorithm (ClinicalTrials.gov, NCT02504294).

Keywords: Anemia; Biosimilar; Chronic kidney disease; Dialysis; Epoetin alfa; Epoetin alfa-epbx; Erythropoietin; Switching.

Publication types

  • Clinical Trial, Phase III
  • Equivalence Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Anemia / blood
  • Anemia / drug therapy*
  • Anemia / etiology
  • Biosimilar Pharmaceuticals / administration & dosage*
  • Biosimilar Pharmaceuticals / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Dosage Calculations
  • Drug Substitution
  • Epoetin Alfa / administration & dosage*
  • Epoetin Alfa / adverse effects
  • Female
  • Hematinics / administration & dosage*
  • Hematinics / adverse effects
  • Hemoglobins / analysis
  • Humans
  • Injections, Intravenous
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Renal Dialysis / adverse effects
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult


  • Biosimilar Pharmaceuticals
  • Hematinics
  • Hemoglobins
  • Epoetin Alfa

Associated data

  • ClinicalTrials.gov/NCT02504294