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Observational Study
. 2018 Aug;32(4):367-375.
doi: 10.1007/s40259-018-0293-2.

Comparative Safety of Originator and Biosimilar Epoetin Alfa Drugs: An Observational Prospective Multicenter Study

Giovanna Stoppa  1 , Carmen D'Amore  2 , Anita Conforti  1 , Giuseppe Traversa  3 , Mauro Venegoni  1 , Maurizio Taglialatela  4 , Roberto Leone  5 ; ESAVIEW Study Group
Collaborators, Affiliations
Observational Study

Comparative Safety of Originator and Biosimilar Epoetin Alfa Drugs: An Observational Prospective Multicenter Study

Giovanna Stoppa et al. BioDrugs. 2018 Aug.

Abstract

Background: Erythropoiesis-stimulating agents (ESAs) are biological molecules approved for the treatment of anemia associated with chronic renal failure. Biosimilars were licensed for use in Europe in 2007.

Aim: This study aimed to compare the safety profile of biosimilars with respect to the reference product in a nephrology setting.

Methods: A prospective study was conducted in four Italian regions between 1 October 2013 and 30 June 2015. The study population included patients aged ≥ 18 years undergoing hemodialysis and treated with epoetins as per the clinical practice of the participating centers. The two comparison cohorts included patients treated with either an originator or a biosimilar epoetin alfa. Each patient was followed up until occurrence of any safety outcome of interest (grouped into three major categories), switch to a different ESA product, transplant or peritoneal dialysis, death, or end of the study period, whichever came first.

Results: Overall, 867 subjects were included in the study (originator: N = 423; biosimilar: N = 444). Biosimilar users were older than originator users (median age of 76 vs 64 years, respectively), more frequently affected by arrhythmia (29.3 vs 22.5%), and less frequently candidates for transplantation (3.8 vs 18.2%). Cox-regression analysis showed no increase in risk of safety outcomes in biosimilar users, even after adjusting for confounding factors: 1.0 (95% confidence interval [CI] 0.7-1.3) for any outcomes; 1.1 (95% CI 0.7-1.8) for problems related to dialysis device; 0.9 (95% CI 0.6-1.5) for cardio- and cerebro-vascular conditions; 0.9 (95% CI 0.6-1.5) for infections.

Conclusion: This study confirms the comparable safety profiles of originator and biosimilar epoetin alfa drugs when used in patients receiving dialysis.

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Conflict of interest statement

Funding

This study was conducted in the context of the “Monitoring of adverse drug reactions by biological and biosimilar products” project, which was funded by the Italian Medicines Agency (Agenzia Italiana del Farmaco [AIFA]).

Conflicts of interest

Giovanna Stoppa, Carmen D’Amore, Anita Conforti, Giuseppe Traversa, Mauro Venegoni, Maurizio Taglialatela, and Roberto Leone declared that they have no conflicts of interest.

Ethical approval

The study protocol was approved by the Ethics Committees of the participating hospitals. Written informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
Flow diagram of patients enrolled in the study. CKD chronic kidney disease, ESA erythropoiesis-stimulating agents
Fig. 2
Fig. 2
Kaplan–Meier survival analysis for outcomes grouped into three major categories and considered all together
See this image and copyright information in PMC

References

    1. Hörbrand F, Bramlage P, Fischaleck J, Hasford J, Brunkhorst R. A population-based study comparing biosimilar versus originator erythropoiesis-stimulating agent consumption in 6,117 patients with renal anaemia. Eur J Clin Pharmacol. 2013;69(4):929–936. doi: 10.1007/s00228-012-1412-5. - DOI - PubMed
    1. Guideline on non-clinical and clinical development of similar biological medicinal products containing recombinant erythropoietins (Revision). http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guidelin.... Accessed 10 Jan 2018.
    1. Revision of the position on biosimilar drugs by the Italian Society of Pharmacology: working paper 2014. https://www.sifweb.org/documenti/PositionPaper/position_paper_2009-04-01. Accessed 11 January 2018.
    1. Pani L, Montilla S, Pimpinella G, Bertini Malgarini R. Biosimilars: the paradox of sharing the same pharmacological action without full chemical identity. Expert Opin Biol Ther. 2013;13(10):1343–1346. doi: 10.1517/14712598.2013.815722. - DOI - PubMed
    1. Italian Medicines Agency. The medicines utilization monitoring centre (OsMed). National report on medicines use in Italy. Year 2013 http://www.aifa.gov.it/sites/default/files/Rapporto_OsMED_2013.pdf. Accessed 10 Jan 2018.

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