Introduction: As consequence of Italian debt rescheduling program, administrative orders were issued by Campania Region (DGRC: 15/2009, 34/2012, 25/2012, 27/2013, 114/2013) to regulate erythropoiesis-stimulating agents (ESAs) prescriptive appropriateness. According to regional dispositions, the use of biosimilar ESA should be promoted in all ESA-naïve patients with anemia due to kidney disorders. Also, ESA related adverse events (AE) should be overseen and therapeutic switch among different ESA products should be discouraged. Therefore, in April 2014, a pilot program was plan (i) to control ESA prescriptions appropriateness within ASL Napoli 1 Centro, (ii) to optimize and improve administrative procedures related to ESA prescriptions and (iii) to create a therapeutic switch and AE registry. Moreover, aiming at facilitating health care access, a new integrated care pathway was designed for hemodialysis patients.
Materials and Methods: A one-month retrospective analysis was conducted. Data on original and biosimilar ESA prescriptions, consumption, and therapeutic switch between original and biosimilar agents in 17 hemodialysis units and in 10 pharmacies on the ASL Napoli 1 Centro district (local pharmacies) were obtained from ASL database system and analyzed by a working group. Also, a single-patient and a unit-chart and an electronic database were created to standardize and organize obtained data. The working group also delineated the new integrated clinical-therapeutic pathway together with clinicians, patients and administrative managers to reduce drugs supply difficulties.
Results: In June 2014, in 376 haemodialysis patients, ESA prescriptions were distributed as follow: 39.10% received Epoetina beta (Neorecormon®), 30.63% received Darbepoetina alfa (Aranesp®), 11.41% received Epoetina zeta (Retacrit®), 10.04% received Epoetina alfa Biosimilare (Binocrit®), 8.42% received Epoetina alfa (Eprex®) and 0.40% received Metossipolietilenglicole Epoetina beta (Mircera®). Biosimilar ESAs were prescribed as first choice only in 14.55% of all ESA prescriptions and 29 therapeutic switch were observed.
In 515 patients with anaemia due to kidney disorders, ESA prescriptions were distributed as follow: 42.40% received Darbepoetina alfa (Aranesp®), 25.40% received Epoetina zeta (Retacrit®), 19.37% received Epoetina beta (Neorecormon®), 9.10% received Epoetina alfa (Eprex®), 3.73% received Metossipolietilenglicole Epoetina beta (Mircera®). Biosimilar ESAs were prescribed as first choice only in 17.66% and 19 therapeutic switch were observed.
In the single-patient chart, we recorded data on: adverse reactions to erythropoietins, medical reasons for choosing an original instead of a biosimilar drug in ESA-naïve patients, reasons for therapeutic switch; in the unit chart, we recorded on a monthly basis for each haemodialysis unit: number of patients, their haemoglobin levels (target level 11-12 g/dl), dosage and type of ESA prescribed, distributed and administered; in the database, we recorded data on therapy and lab values of all haemodialysis patients, and data on haemodialysis units and clinicians in order to classify and organize obtained data.
Also, ESAs’ distribution process was centralized and delivery services improved, to enhance territorial supply in local pharmacies and to control prescriptive appropriateness.
Conclusions: In light of the recent AIFA position statement on the pharmacological equivalence of Alfa-, Beta- and Biosimilar erythtropoietins, further investigations are needed on the prevalent use of Epoetina-Beta in anaemic patients. The excessive number of therapeutic switches identified in our analysis requires a more detailed control of ESAs prescriptions. Moreover, the high number of prescriptions of Darbepoetina alfa suggests the need to better define, in conjunction with clinicians, criteria for prescribing a long- or a short acting erythropoietin.

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Key words: erythropoietins, ESA, biosimilar, anemia, kidney, hemodialysis, naïve