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

European Journal of Clinical Pharmacology volume 74, pages 805–810 (2018)Cite this article

Abstract

Purpose

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).

Methods

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.

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).

Conclusions

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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References

  1. Palmer SC, Saglimbene V, Mavridis D, Salanti G, Craig JC, Tonelli M, Wiebe N, GFM S (2014) Erythropoiesis-stimulating agents for anaemia in adults with chronic kidney disease: a network meta-analysis. Cochrane Database Syst Rev 8:CD010590. https://doi.org/10.1002/14651858.CD010590.pub2

    Google Scholar 

  2. Guideline on non-clinical and clinical development of similar biological medicinal products containing recombinant erythropoietins, MEA/CHMP/BMWP/301636/2008, 18 March 2010 - http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/04/WC500089474.pdf. Accessed 21 Sept 2017

  3. Azevedo V, Hassett B, Fonseca JE, Atsumi T, Coindreau J, Jacobs I, Mahgoub E, O’Brien J, Singh E, Vicik S, Fitzpatrick B (2016) Differentiating biosimilarity and comparability in biotherapeutics. Clin Rheumatol 35(12):2877–2886. https://doi.org/10.1007/s10067-016-3427-2

    Article  PubMed  Google Scholar 

  4. http://www.kidney.org/atoz/content/gfr. Accessed 21 Sept 2017

  5. Hörbrand F, Bramlage P, Fischaleck J, Hasford J, Brunkhorst R (2013) A population-based study comparing biosimilar versus originator erythropoiesis-stimulating agent consumption in 6,117 patients with renal anaemia. Eur J Clin Pharmacol 69(4):929–936. https://doi.org/10.1007/s00228-012-1412-5

    Article  PubMed  Google Scholar 

  6. Sorgel F, Thyroff-Friesinger U, Vetter A, Vens-Cappell B, Kinzig M (2009) Bioequivalence of HX575 (recombinant human epoetin alfa) and a comparator epoetin alfa after multiple subcutaneous administrations. Pharmacology 83(2):122–130. https://doi.org/10.1159/000189027

    Article  PubMed  Google Scholar 

  7. Haag-Weber M, Vetter A, Thyroff-Friesinger U (2009) Therapeutic equivalence, long-term efficacy and safety of HX575 in the treatment of anemia in chronic renal failure patients receiving hemodialysis. Clin Nephrol 72(5):380–390

    CAS  PubMed  Google Scholar 

  8. Wizemann V, Rutkowski B, Baldamus C, Scigalla P, Koytchev R (2009) Comparison of the therapeutic effects of epoetin zeta to epoetin alfa in the maintenance phase of renal anaemia treatment. Curr Med Res Opin 24(3):625–637

    Article  Google Scholar 

  9. Krivoshiev S, Todorov VV, Manitius J, Czekalski S, Scigalla P, Koytchev R (2009) Comparison of the therapeutic effects of epoetin zeta and epoetin alpha in the correction of renal anaemia. Curr Med Res Opin 24(5):1407–1415

    Article  Google Scholar 

  10. Więcek A, Ahmed I, Scigalla P, Koytchev R (2010) Switching epoetin alfa and epoetin zeta in patients with renal anemia on dialysis: posthoc analysis. Adv Ther 27(12):941–952. https://doi.org/10.1007/s12325-010-0080-z

    Article  PubMed  Google Scholar 

  11. Ingrasciotta Y, Giorgianni F, Marcianò I, Bolcato J, Pirolo R, Chinellato A, Ientile V, Santoro D, Genazzani AA, Alibrandi A, Fontana A, Caputi AP, Trifirò G (2016) Comparative effectiveness of biosimilar, reference product and other erythropoiesis-stimulating agents (ESAs) still covered by patent in chronic kidney disease and cancer patients: an Italian population-based study. PLoS One 11(5):e0155805. https://doi.org/10.1371/journal.pone.0155805 17

    Article  PubMed  PubMed Central  Google Scholar 

  12. Cutroneo PM, Isgrò V, Russo A, Ientile V, Sottosanti L, Pimpinella G, Conforti A, Moretti U, Caputi AP, Trifirò G (2014) Safety profile of biological medicines as compared with non-biologicals: an analysis of the Italian spontaneous reporting system database. Drug Saf 37(11):961–970. https://doi.org/10.1007/s40264-014-0224-1

    Article  PubMed  Google Scholar 

  13. Renwick MJ, Smolina K, Gladstone EJ, Weymann D, Morgan SG (2016) Postmarket policy considerations for biosimilar oncology drugs. Lancet Oncol 17(1):e31–e38. https://doi.org/10.1016/S1470-2045(15)00381-2

    Article  PubMed  Google Scholar 

  14. Grozdanova A, Netkovska KA, Sterjev Z, Naumovska Z, Zarevski R, Dimovski A, Suturkova L (2016) Biosimilar medical products—licensing, pharmacovigilance and interchangeability. Pril (Makedon Akad Nauk Umet Odd Med Nauki) 37(1):27–36. https://doi.org/10.1515/prilozi-2016-0006

  15. Jepsen P, Johnsen SP, Gillman MW, Sørensen HT (2004 Aug) Interpretation of observational studies. Heart 90(8):956–960. https://doi.org/10.1136/hrt.2003.017269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

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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Authors and Affiliations

  1. Unit of Pharmacology, Department of Medical and Surgical Sciences, University of Bologna, via Irnerio 48, 40126, Bologna, Italy

    Domenico Motola, Alberto Vaccheri, Monia Donati & Giulia Bonaldo

  2. CINECA - Interuniversity Consortium - Health Department, via Magnanelli 6/3, 40033, Casalecchio di Reno, BO, Italy

    Andrea Roncadori & Anna Covezzoli

  3. Department of Clinical Pharmacy, Mediterranean Institute for Transplantation and Advanced Specialised Therapies (ISMETT), Palermo, Italy

    Piera Polidori

  4. Department of Pharmacy, Azienda Ospedaliera Ospedali Riuniti Marche Nord, Pesaro, Italy

    Stefano Bianchi

Authors
  1. Domenico Motola
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  2. Alberto Vaccheri
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  3. Andrea Roncadori
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  4. Monia Donati
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  5. Giulia Bonaldo
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  6. Anna Covezzoli
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  7. Piera Polidori
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  8. Stefano Bianchi
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Corresponding author

Correspondence to Domenico Motola.

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Conflict of interest

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).

Ethical approval

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). https://doi.org/10.1007/s00228-018-2428-2

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  • DOI: https://doi.org/10.1007/s00228-018-2428-2

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