Antibody-mediated pure red cell aplasia (PRCA): epidemiology, immunogenicity and risks

Although epoetin-induced antibody (Ab)-mediated pure red cell aplasia (PRCA) was very rare prior to 1998, a large increase in the number of global cases was observed from 1999 to 2002 in patients treated with erythropoiesis-stimulating agents (ESAs) for the anaemia associated with chronic kidney disease (CKD). The number of global cases of this immunological form of PRCA has declined precipitously since 2003 following increased awareness of this disorder and changes in the handling and administration of the formulation of epoetin-alpha (EPO) that was associated with the majority of cases. Current recommendations state that patients should stop treatment immediately following a diagnosis of Ab-mediated PRCA and not resume treatment with the same or another ESA. The feasibility of re-treatment following remission from PRCA or during ongoing immunosuppressive therapy is currently under investigation. The immunological mechanism for developing Ab-mediated PRCA is unknown, but a variety of factors may increase the immunogenicity of epoetin or other ESAs. Product-related factors that have the potential to impact on immunogenicity include sequence variations in proteins, the degree and nature of protein glycosylation, the manufacturing process, handling and storage, and components and properties of the product formulation. Patient-related factors associated with developing Ab-mediated PRCA include skin reactions, immune status and treatment history. Increased awareness among physicians of the factors contributing to the development of PRCA and its distinguishing clinical features has coincided with studies aimed at identifying effective therapies for this disorder. A number of immunosuppressive therapies have been shown recently to reconstitute effectively the erythropoietic response in patients with PRCA. However, therapeutic approaches for this serious immunological reaction to recombinant ESAs remain investigative.