Pure red cell aplasia after treatment of renal anaemia with epoetin theta

Abstract

The treatment of renal anaemia in patients with chronic kidney disease (CKD) has always been a challenge. The introduction of erythropoiesis-stimulating agents (ESAs) appeared to be a milestone, enabling physicians to avoid red blood cell transfusions in this patient group. In the last decade, however, these assumed advances were tarnished by the occurrence of a new condition: ESA-induced, antibody-mediated, pure red cell aplasia (PRCA). PRCA is characterized by the combination of anaemia, low reticulocyte count, absence of erythroblasts in the bone marrow, resistance to therapy with ESAs and detection of neutralizing antibodies against erythropoietin. The exposure-adjusted incidence of 0.02–0.03 per 10 000 patient years is considered rare. In the years 2002 and 2003, it peaked, however, at an incidence of 4.5 cases per 10 000 patient years, mainly caused by a preparation of epoetin alfa [1]. Hypothetic explanations concerning the PRCA-inducing potential of this specific preparation of epoetin alfa have been published [1]. Nevertheless, we have to accept the possibility that all ESAs can induce an immunological response in the form of neutralizing antibodies [2, 3]. Because of the complexities of manufacturing biopharmaceuticals, there are safety concerns regarding me-too biologicals and biosimilars and the automatic substitution of originator drugs for economic reasons [4, 5]. In the interest of patient safety, the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines only recommend the use of biosimilars approved by an independent regulatory agency that are subject to pharmacovigilance plans [6]. We report on a patient treated with the originator drugs such as epoetin theta, epoetin beta and darbepoetin alfa, who developed ESA-induced PRCA. The repetitive switching of agents hampered our ability to attribute PRCA to the appropriate agent.