Authors: Walter H Hörl
Publish Date: 2013/01/22
Volume: 73, Issue: 2, Pages: 117-130
Abstract
Erythropoiesisstimulating agents ESAs have become a hallmark of anaemia therapy in patients with chronic kidney disease CKD Although different ESAs are available for the treatment of renal anaemia each nephrologist should select a single ESA for an individual patient Epoetin alfa and epoetin beta have been used 1–3 times weekly but extendedinterval dosing up to every 4 weeks is also effective in a substantial majority of CKD patients However the epoetin dose necessary to achieve or maintain target haemoglobin Hb levels increases substantially as the dosing interval increases Subcutaneous administration of shortacting ESAs is more effective than the intravenous route of administration Darbepoetin alfa and the continuous erythropoietin receptor activator CERA have been developed as a treatment for anaemia with extended administration intervals every 2 weeks and every 4 weeks respectively Dose requirements for these longacting ESAs are independent of the route of administration Patents of shortacting ESAs have expired which has opened the field for biosimilars Epoetin biosimilars approved by the European Medicines Agency EMA or the US Food and Drug Administration FDA have been shown to have a comparable efficacy and safety profile to their originators An alarming increase in pure red cell aplasia PRCA in Thailand with followon epoetins manufactured in Asia but also those manufactured in Latin America indicates that stringent countryspecific approval and pharmacovigilance protocols for ESAs manufactured in nonNorth American and nonEU European countries are urgently needed Two PRCA cases occurring with subcutaneous HX575 one certain one likely indicate that chances of inducing a more immunogenic product are unpredictable even with a biosimilar epoetin approved under the EMA biosimilar approval pathway Phase III clinical trials with peginesatide a pegylated synthetic peptidebased ESA without any homology to erythropoietin raised safety concerns in nondialysis CKD patients but not in dialysis patientsNo sources of funding were used to conduct this study or prepare this manuscript Professor Walter H Hörl has associations with the following companies Amgen speakers’ bureau Sandoz consultant Hexal consultant speakers’ bureau Fresenius speakers’ bureau research support Vifor consultant speakers’ bureau grant/research support Medice speakers’ bureau Abbott speakers’ bureau and Takeda consultant
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