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Comparative effectiveness and safety of erythropoiesis-stimulating agents (biosimilars vs originators) in clinical practice: a population-based cohort study in Italy
  1. Francesco Trotta1,
  2. Valeria Belleudi1,
  3. Danilo Fusco1,
  4. Laura Amato1,
  5. Alessandra Mecozzi2,
  6. Flavia Mayer1,
  7. Massimo Sansone2,
  8. Marina Davoli1,
  9. Antonio Addis1
  1. 1Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
  2. 2Drug Policy Area, General Directorate for Health, The Lazio Region, Rome, Italy
  1. Correspondence to Dr Francesco Trotta; f.trotta{at}


Objectives To evaluate the benefit/risk profile of epoetin α biosimilar with the erythropoiesis-stimulating agents (ESAs) originators when administered to naïve patients from clinical practice.

Design Population-based observational cohort study.

Setting All residents in the Lazio Region, Italy, with chronic kidney disease (CKD) or cancer retrieved from the Electronic Therapeutic Plan (ETP) Register for ESA between 2012 and 2014.

Participants Overall, 13 470 incident ESA users were available for the analysis, 8161 in the CKD and 5309 in the oncology setting, respectively.

Interventions ESAs identified through the ATC B03XA were divided into 3 groups: (1) biosimilars; (2) epoetin α originator and (3) other originators. Patients were exposed to ESAs from the date of activation of the ETP, until the end of a 6-month follow-up period.

Outcome measures Effectiveness (all-cause mortality and blood transfusion) and safety (major cardiovascular events, blood dyscrasia). A composite outcome including all-cause mortality, blood transfusion and major cardiovascular events was predefined. HRs of any outcome were estimated through Cox regression.

Results We found no differences between patients on biosimilars or all originators with regard to the risk estimates of all-cause mortality, blood transfusion, major cardiovascular events and blood dyscrasia in the CKD setting. The composite outcome confirmed these results (biosimilars vs epoetin α originators: adjusted HR=1.02, 95% CI 0.78 to 1.33; biosimilars vs other originators: adjusted HR=1.09, 95% CI 0.85 to 1.41). Comparable risk estimates were observed between biosimilars and all originators in the oncology setting.

Conclusions In both settings, our findings are suggestive of no difference between biosimilars and originators on relevant effectiveness and safety outcomes. This study may contribute to settling future drug policy for the health services and provides reassurance on the approval pathway for biosimilars. The oncology setting merits further research, taking into account tumour types, tumour stage and anticancer chemotherapy administered.

  • Comparative effectiveness
  • biosimilar
  • erythropoiesis-stimulating agents
  • cohort study
  • real life data

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

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  • MD and AA equally shared the oversight of this work.

  • Contributors FT and AA conceived the study. FT, VB, AA, DF, LA and MD designed the study. FT, VB, AA, DF and FM analysed the data. FT and AA wrote the manuscript. FT, VB, AA, DF, LA and FM contributed to the discussion and reviewed the manuscript. All authors saw, commented on and approved the final version of the paper. AA and MD are the guarantors.

  • Funding Only public employees of the regional health authorities were involved in conceiving, planning and conducting the study.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The authors are willing to collaborate in answering further research questions and to participate in systematic reviews or meta-analyses.

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