Antibody-mediated pure red cell aplasia related with epoetin-beta pegol (C.E.R.A.) as an erythropoietic agent: case report of a dialysis patient

Abstract

Background: Erythropoietin-stimulating agents (ESAs) are used to treat anemia in patients with chronic kidney disease, enabling maintenance of stable hemoglobin levels and eliminating the need for multiple transfusions. Epoetin-beta pegol (C.E.R.A.) is a continuous erythropoietin receptor activator created by integrating a large methoxy-polyethylene-glycol-polymer chain into the erythropoietin molecule, which provides it with a longer halflife. On rare occasions, cases of antibody-mediated pure red cell aplasia (PRCA) related to ESAs are reported. They are characterized by abrupt onset of severe transfusion-dependent anemia, despite ESA therapy. We herein report a case of antibody-mediated PRCA in a dialysis patient receiving C.E.R.A. Case presentation: A 44-year-old man with end-stage renal failure had been receiving continuous ambulatory peritoneal dialysis for 2 years. C.E.R.A. was administered subcutaneously as a sole ESA once a month at the hospital since 4 years ago for the treatment of renal anemia and his hemoglobin level was well controlled at 12 g/dl. From 10 months before diagnosis, however, his hemoglobin level suddenly declined, necessitating frequent transfusions. Based on the results of a bone marrow examination and detection of anti-C.E.R.A. antibodies, the patient was diagnosed with antibody-mediated PRCA. After successful elimination of the antibodies using oral prednisolone plus cyclosporine, the patient was re-administrated C.E.R.A. intravenously, as there are few reports of antibodymediated PRCA related to ESA using that administration route. He responded to the C.E.R.A., and his anemia dramatically improved, eliminating the need for blood transfusions. Conclusions: This is the first reported case of recovery from an antibody-mediated PRCA with C.E.R.A. after its readministration following a reversal of the antibody. It has been suggested that the additional large pegylation chain makes C.E.R.A. less likely to trigger antibody generation than other ESAs. Following successful treatment of antibodymediated PRCA using immunosuppressive therapy, C.E.R.A. can be re-administered intravenously to treat renal anemia.

A 46-Year-Old Thai Woman with Secondary Acquired Pure Red Cell Aplasia Due to Treatment with Recombinant Erythropoietin While on Dialysis for End-Stage Renal Disease Who Recovered Following ABO-Incompatible Kidney Transplantation

“…Epoetin-beta pegol (continuous erythropoietin receptor activator; CERA), a third-generation ESA, has also been reported in cases of confirmed antibody-mediated PRCA related to CERA. Pfizer’s Biosimilar Retacrit ® is biosimilar to Epogen® and Procrit ® (epoetin alfa) [ 11 ]. Due to exposure to different brands of ESA, which can increase the risk of PRCA, the timing of the exposure, and the route of administration, the anemia in this patient was most likely from anti-ESA antibody-mediated PRCA.…”

“…The main rationale for using immunosuppressives is to suppress antibody production [ 10 ]. A large retrospective study showed that none of the PRCA patients who did not receive immunosuppressives were considered cured, whereas 56%, 87%, 67%, and 100% were considered cured when treated with steroid, steroid plus cyclophosphamide, cyclosporine, and kidney transplantation, respectively [ 11 ]. These results suggest that immunosuppressive treatment can accelerate recovery from anti-EPO antibody-mediated PRCA.…”

“…The most effective first-line treatment of idiopathic PRCA is cyclosporine A (CsA) administered at a starting dose of 2 to 6 mg/kg per day (in divided doses), possibly combined with steroid (prednisone at 30 mg/day) with a rapid taper, yielding an overall response rate (ORR) of about 65% to 87%. There are some case reports of PRCA remission after kidney transplantation, but the biological mechanisms are not well understood [ 11 – 14 ]. A possible hypothesis is that immunosuppression prevents the formation of antibodies, and endogenous erythropoietin production from the graft helps to attain PRCA remission [ 15 ].…”

Cutaneous leukocytoclastic vasculitis induced by continuous erythropoietin receptor activator

“… 7 Indeed, several cases of anaphylaxis and pure red cell aplasia have been reported, indicating that CERA can also promote biopharmaceutical-related immune responses. 9 , 10 …”

Successful Treatment of Antibody-mediated Pure Red Cell Aplasia Induced by Continuous Erythropoietin Receptor Activator with Prednisolone

“…Continuous erythropoietin receptor activator (CERA) is a third-generation ESA with a methoxy-polyethylene glycol polymer chain integrated into the erythropoietin molecule and a longer elimination half-life than previous ESAs ( 4 ). Few cases of PRCA induced by CERA and presenting with anti-epoetin beta pegol antibody have been reported ( 5 , 6 ).…”