title: Risk of pure red cell aplasia in patients with hepatitis C receiving antiviral therapy and an erythropoiesis-stimulating agent.
abstract: Antibody-mediated pure red cell aplasia (PRCA) has been primarily observed in patients with chronic kidney disease treated with an erythropoiesis-stimulating agent (ESA); only a few anecdotal cases have been reported in other patient populations. We searched the Amgen Global Safety Adverse Event Database and identified 14 patients with hepatitis C who developed severe anemia, anti-erythropoietin antibodies, and bone marrow biopsy-proven PRCA, while receiving interferon therapy (with or without ribavirin) and an ESA. During the follow-up period and after ESA treatment stopped, 11 patients no longer required transfusions and 3 did. Analysis of antibody isotypes showed that, contrary to reports of patients with chronic kidney disease, immunoglobulin G1 was the predominant isotype rather than immunoglobulin G4 (immunoglobulin G4 was detected in only 1 of 6 patients). Epitope mapping showed the anti-erythropoietin antibodies bound domains required for receptor binding. Therefore, the potential benefits of ESA therapy must be weighed against the risk for PRCA in patients with hepatitis C who are receiving treatment with interferon and ribavirin.
authors.affiliation: Clinical Development, Amgen Inc, Thousand Oaks, California.
authors.forename: Jerome
authors.initials: J
authors.lastname: Rossert
authors.affiliation: Global Safety, Amgen Inc, Thousand Oaks, California.
authors.forename: Susan
authors.initials: S
authors.lastname: Yue
authors.affiliation: Global Safety, Amgen Inc, Thousand Oaks, California.
authors.forename: Karen
authors.initials: K
authors.lastname: Smirnakis
authors.affiliation: Clinical Immunology and Biologic Sample Management, Amgen Inc, Thousand Oaks, California.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Mytych
authors.affiliation: Global Safety, Amgen Inc, Thousand Oaks, California.
authors.forename: Larry
authors.initials: L
authors.lastname: Johnson
authors.affiliation: Global Safety, Amgen Inc, Thousand Oaks, California.
authors.forename: Elias
authors.initials: E
authors.lastname: Kouchakji
authors.affiliation: AP-HP, INSERM U 1009 and Pierre and Marie Curie University, Paris, France. Electronic address: nicole.casadevall@sat.aphp.fr.
authors.forename: Nicole
authors.initials: N
authors.lastname: Casadevall
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use; D018604:Epitope Mapping; D004921:Erythropoietin / Q000276:immunology; D006397:Hematinics / Q000009:adverse effects*; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D008875:Middle Aged; D012010:Red-Cell Aplasia, Pure / Q000150:complications* / Q000276:immunology
chemical_list: D000906:Antibodies; D000998:Antiviral Agents; D006397:Hematinics; D007074:Immunoglobulin G; D004921:Erythropoietin
keywords: CKD; Complication; ESA; HCV; HCV Infection; Hepatitis C Virus; IFN; Ig; PRCA; RBV; Side Effect; chronic kidney disease; erythropoiesis-stimulating agent; hepatitis C virus; immunoglobulin; interferon; pure red cell aplasia; ribavirin