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Comparative risk/benefit profile of biosimilar and originator erythropoiesis-stimulating agents (ESAs): data from an Italian observational study in nephrology



The aim of this multicenter prospective study was to evaluate efficacy and safety of biosimilar erythropoiesis-stimulating agents (ESAs) vs originator, based on data from clinical practice in patients with chronic kidney disease (CKD).


We collected data of the patients with diagnosis of CKD on conservative treatment from nine Italian structures. Patients were enrolled applying different exclusion criteria, and various individual parameters were registered at the beginning for descriptive analysis. Patients were treated with epoetin alfa, beta, and darbepoetin as originator and epoetin zeta as biosimilar. Hemoglobin levels have been analyzed at baseline and after 3, 6, and 12 months. Descriptive statistics were used to analyze the results.


At baseline, 47 patients were in the biosimilar group and 57 in the originator; the basal level of hemoglobin was similar between the groups (mean Hb 9.4 and 9.3 g/dL, respectively). Median age, weight, and comorbidities were almost comparable. After 3 months, 44 patients remained in the biosimilar group and 48 in the originator; hemoglobin increase was significantly greater in patients treated with biosimilar [absolute increase 1.6 vs 1.0 g/dL, p < 0.001]. After 6 and 12 months, number of patients fall furthermore. Hemoglobin levels increased more in the biosimilar group after 6 months (2.1 vs 1.1 g/dL, p < 0.001) and 12 months (2.0 vs 1.0 g/dL, p < 0.001).


Biosimilar ESAs have similar risk/benefit profile compared to originators. Our data are in agreement with relevant scientific literature and, on the other hand, they are in contrast with common thought that considers biosimilar less efficacious and less safe than originators.

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We wish to thank the pharmacists and doctors who participated in the study: Anna Fornero, Valentina Pelleu and Danila Gabrielli (Azienda USL Valle d’Aosta), Simona Spolti and Ugo Teatini (Azienda ospedaliera di Garbagnate), Loredana Scoccia (ASUR MARCHE Area Vasta, 3 Macerata), Elena Galfrascoli and Gaetana Muserra (Azienda Ospedaliera Fatebenefratelli e Oftalmico, Milano), Marika Rotolo (Presidio ospedaliero Abele Ajello di Mazara del Vallo - Trapani), Chiara Casellato (USSL 19 Adria Regione Veneto), Vincenzo Picerno (Ente Ecclesiastico Ospedale Generale Regionale F. Miulli - Acquaviva delle Fonti) and Giorgia Russo (Azienda Ospedaliero-Universitaria di Ferrara).

Contributions of authors

D Motola and A Vaccheri drafted the initial manuscript; A Roncadori and A Covezzoli performed the statistical analysis. S Bianchi (principal investigator), M Donati, P Polidori and G Bonaldo reviewed and revised the manuscript; all authors contributed to conceptualization, design, and analysis, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work. All the authors approved the final version of the manuscript. No honorarium, grant, or other form of payment was given to anyone to produce the manuscript.

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Correspondence to Domenico Motola.

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The authors declare no conflict of interest for the submitted work.

The study has been performed with a non-profit economic contribution funded by SIFO (Italian Society of Hospital Pharmacy).

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Motola, D., Vaccheri, A., Roncadori, A. et al. Comparative risk/benefit profile of biosimilar and originator erythropoiesis-stimulating agents (ESAs): data from an Italian observational study in nephrology. Eur J Clin Pharmacol 74, 805–810 (2018).

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