title: Differentiating factors between erythropoiesis-stimulating agents: an update to selection for anaemia of chronic kidney disease.
abstract: Erythropoiesis-stimulating 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 extended-interval 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 short-acting 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 long-acting ESAs are independent of the route of administration. Patents of short-acting 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 follow-on epoetins manufactured in Asia (but also those manufactured in Latin America) indicates that stringent country-specific approval and pharmacovigilance protocols for ESAs manufactured in non-North American and non-EU 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 peptide-based ESA without any homology to erythropoietin raised safety concerns in non-dialysis CKD patients but not in dialysis patients.
authors: Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. walter.hoerl@meduniwien.ac.at
authors: Walter H
authors: WH
authors: Hörl
mesh_terms: D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D059451:Biosimilar Pharmaceuticals; D000068256:Darbepoetin alfa; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D006397:Hematinics / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous / Q000379:methods; D007279:Injections, Subcutaneous / Q000379:methods; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012010:Red-Cell Aplasia, Pure / Q000139:chemically induced; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D059451:Biosimilar Pharmaceuticals; D006397:Hematinics; D010455:Peptides; C508420:continuous erythropoietin receptor activator; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D011092:Polyethylene Glycols; C556270:peginesatide