Journal name: Biologics: Targets and Therapy Article Designation: ORIGinal RESEARCH Year: 2016 Volume: 10 Biologics: Targets and Therapy Dovepress Running head verso: Perrone et al Running head recto: Pharmacoutilization of epoetins in naïve patients open access to scientific and medical research DOI: http://dx.doi.org/10.2147/BTT.S114625 Open Access Full Text Article ORIGINAL RESEARCH Pharmacoutilization of epoetins in naïve patients with hematological malignancies in an unselected Italian population under clinical practice setting: a comparative analysis between originator and biosimilars Valentina Perrone1 Aim: The purpose of this study was to assess the prescription of epoetins and consumption Stefania Saragoni1 of health care resources (in terms of drug treatments) in naïve patients with hematological Stefano Buda1 malignancies in a real-world setting; in particular, we compared the results between reference Alessandro Broccoli2 product and biosimilar products. Luca Degli Esposti1 Methods: An observational retrospective study based on administrative and laboratory databases For personal use only. of three local health units was conducted. All adults diagnosed with hematological malignancies 1 CliCon S.r.l., Health, Economics and who had received at least one epoetin (either reference product or biosimilars) prescription & Outcomes Research, Ravenna, 2Institute of Hematology “L. e A. for the first time between 1 January 2010 and 30 April 2012 (enrollment period) were included. Seràgnoli”, University of Bologna, The date of the first prescription of epoetin within the enrollment period was defined as index Bologna, Italy date (ID). Patients were followed up for 4 weeks after ID (follow-up period) and were inves- tigated for the 1-year period before the ID. The difference between the last hemoglobin (Hb) measurement after ID and the one prior to ID (ΔHb) was evaluated. The drug cost analysis was conducted from the perspective of the Italian National Health System. Results: Overall, 69 patients were included in the study; 48 of them received reference epoetin product and 21 received biosimilars as first prescription. Among reference product users, the mean ± standard deviation (SD) age was 62.5±14.7 years; this cohort of patients was slightly Biologics: Targets and Therapy downloaded from https://www.dovepress.com/ by 54.70.40.11 on 10-Dec-2018 significantly younger than the biosimilar users (71.8±11.8 years). The mean ± SD overall Hb level prior to treatment was lower among patients who started with biosimilar products (9.6±1.1 g/dL) compared to those who started with a reference product (10.1±2.1 g/dL). No significant differences in ΔHb were observed between biosimilar and originator groups during the follow- up period. The mean ± SD cost per patient was €667.98±573.93 and €340.85±235.73 for the reference product and biosimilar users, respectively (p=0.065). Conclusion: Our study showed that the use of biosimilar products might contribute to control- ling health care costs (in terms of drug treatments) for patients with hematological malignancies being maintained by high-quality anemia therapy. Our findings also showed some discordances regarding the most appropriate therapeutic approach in daily clinical practice. Keywords: erythropoiesis-stimulating agents, chemotherapy-induced anemia, biosimilar, Correspondence: Luca Degli Esposti real-world setting CliCon S.r.l., Health, Economics and Outcomes Research, Via Salara, 36, 48100 Ravenna, Italy Introduction Tel +39 544 38393 Anemia is a condition in which the red blood cell mass is insufficient to adequately deliver Fax +39 544 212699 Email [email protected] oxygen to peripheral tissues. Patients with anemia related to cancer, chronic inflammation, submit your manuscript | www.dovepress.com Biologics: Targets and Therapy 2016:10 157–165 157 Dovepress © 2016 Perrone et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work http://dx.doi.org/10.2147/BTT.S114625 you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Powered by TCPDF (www.tcpdf.org) 1 / 1 Perrone et al Dovepress or chronic kidney disease (CKD) generally display a reduced in particular, we compared the results between reference response of endogenous erythropoietin (EPO) to trigger levels product and biosimilar products. of hemoglobin (Hb); this aspect is worsened in those who are concomitantly receiving myelotoxic chemotherapy.1,2 Anemia Methods may significantly impair quality of life, increase cardiovascular Data sources risk, and reduce long-term survival, when left untreated.3 The study was conducted using administrative databases Earlier, treatment options were essentially limited to of three Italian local health units (LHUs), geographically blood transfusions. The introduction of recombinant human distributed throughout the national territory, representing EPO and an erythropoietic stimulating agent (ESA) in 1989 ~550,000 health-assisted individuals. resulted in a major progress in the treatment of anemia and In particular, the following databases were used to retrieve provided a key tool for managing this condition in patients the information: Beneficiaries, Hospital Direct Drugs Distri- with CKD or cancer.4–7 bution Registry, Territorial Pharmacy, Hospital Discharges, In December 2004, the patent of epoetin-alpha (i.e. Ambulatory Care Specialist, Laboratory Analysis (which Eprex®, reference product or originator [Janssen-Cilag, records the date and result of the Hb measurements), and the Neuss, Germany]) expired and this opened the way to Mortalities, where only death dates are reported. biosimilars. Currently, in Europe three biosimilar products The diagnosis and procedures were retrieved using codes have received marketing authorization from the European classified according to the International Classification of Dis- Medicines Agency (EMA): Binocrit® [Sandoz GmbH, eases, Ninth Revision, Clinical Modification (ICD-9-CM). Holzkirchen, Germany] (epoetin-alpha; also known as The information on drug prescriptions was identified through Abseamed® [Medice Arzneimittel Putter GmbH & Co., the International Anatomical Therapeutic Chemical classifi- Iserlohn, Germany] and Epoetin Alfa Hexal® [Hexal Biotech cation system (ATC code). Forschungs GmbH, Holzkirchen, Germany]), Retacrit® To guarantee patient privacy, each subject was assigned an [Hospira, Maidenhead, United Kingdom] (epoetin-zeta; also anonymous univocal numeric code. No identifiers related to For personal use only. called Silapo® [Stada R&D AG, Bad Vilbel, ­Germany]), patients were provided to the researchers. The patient code in and Eporatio® [Ratiopharm GmbH, Ulm, Germany] each database permitted electronic linkage between all data- ( epoetin- theta; also known as Biopoin® [Teva GmbH, Ulm, bases. Informed consent is not required by the LHU ethics Germany]).8 Since 2007, biosimilars of ESAs are available committees for using encrypted retrospective information. on the Italian market.9,10 According to the EMA guidelines, In compliance with the AIFA Determination20 Guidelines a biosimilar is defined as a biological medicinal product for classification and conduction of observational studies on that is developed to be similar to an existing biological (the drugs and AIFA Circular Procedures for launch of observa- “reference medicine”). A biosimilar demonstrates similar- tional studies on drugs, this study was notified to the local ity to the reference medicinal product in terms of quality ethics committee in each participating LHU according to the characteristics, biological activity, safety and efficacy based Italian law regarding the conduct of observational analysis Biologics: Targets and Therapy downloaded from https://www.dovepress.com/ by 54.70.40.11 on 10-Dec-2018 on a comprehensive comparability exercise.11 and the LHU ethics committees approved the study. Although a biosimilar is approved based on its therapeutic equivalence, the interchangeability is still an open question Cohort definition mark;12 nevertheless, in accordance with the recent European This study was an observational retrospective cohort analysis. directives and the last position paper from the Italian Medicines All naïve patients aged ≥18 years who received at least one Agency (AIFA—Agenzia Italiana del Farmaco), biosimilar dispensing of epoetin (biosimilars [epoetin-alpha biosimilars: epoetins may be prescribed to naïve patients;13,14 however, the Binocrit and Abseamed; epoetin-zeta biosimilar: Retacrit] choice to treat a patient with a biological reference product or or their corresponding reference medical product: Eprex biosimilars is a clinical decision entrusted to the physician.13 [ATC code: B03XA01]) during the enrollment period (from Few real-life data and comparative analysis are available 1 January 2010 to 30 April 2012) were considered eligible concerning the use of originator epoetins and biosimilar candidates for analysis and were enrolled. All these ESAs products in the Italian setting.15–19 The objective of the present have been