In Search of Predictors of Switching Between Erythropoiesis-Stimulating Agents in Clinical Practice: A Multi-Regional Cohort Study

BioDrugs. 2020 Feb;34(1):55-64. doi: 10.1007/s40259-019-00385-y.


Background and objectives: Switching between different erythropoiesis-stimulating agents (ESAs) during the first year of therapy is frequent (15-20%), much more so toward reference products than biosimilars. The objectives of this study were to investigate the frequency and identify the potential predictors of switching between biosimilar and originator ESAs during the first year of treatment in patients with chronic kidney disease (CKD), or chemotherapy-related anemia from six large Italian geographic areas in the years 2009-2015.

Methods: A retrospective cohort study was conducted using six Italian regional claims databases (≥ 13 million inhabitants) during 2009-2015. Among incident epoetin users, the frequency of single, multiple, and backward switch during the first year of treatment was evaluated. Using frailty Cox models, potential predictors of first switch were identified. All analyses were stratified by the main indications for use.

Results: Among 102,240 incident epoetin users, 15,853 (15.5%) switched to another epoetin during the first year of therapy; only 18% of these switched to biosimilars. Single switch was more common (62.2% of the switchers) than multiple (23.5%) or backward switch (14.3%). In cancer, the cumulative number of transfusions and iron preparations dispensed, as well as hyperparathyroidism, were predictors of switching. In CKD, the cumulative number of transfusions, number of vitamin A/D preparations dispensed, and CKD severity increased the probability of switching.

Conclusions: Switching between ESAs was frequent in both CKD and cancer patients. The number of cumulative transfusions and severity of disease seemed to affect the switch.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Aged
  • Anemia / drug therapy
  • Biosimilar Pharmaceuticals / therapeutic use
  • Cohort Studies
  • Databases, Factual
  • Epoetin Alfa / pharmacology
  • Erythropoiesis / drug effects*
  • Female
  • Hematinics / therapeutic use*
  • Humans
  • Italy
  • Male
  • Neoplasms / drug therapy
  • Proportional Hazards Models
  • Renal Insufficiency, Chronic / drug therapy
  • Retrospective Studies


  • Biosimilar Pharmaceuticals
  • Hematinics
  • Epoetin Alfa