title: Biosimilar recombinant human erythropoietin induces the production of neutralizing antibodies.
abstract: Recombinant human erythropoietin (r-HuEpo) has been used for the treatment of renal anemia. With the loss of its patent protection, there has been an upsurge of more affordable biosimilar agents, increasing patient access to treatment for these conditions. The complexity of the manufacturing process for these recombinant proteins, however, can result in altered properties that may significantly affect patient safety. As it is not known whether various r-HuEpo products can be safely interchanged, we studied 30 patients with chronic kidney disease treated by subcutaneous injection with biosimilar r-HuEpo and who developed a sudden loss of efficacy. Sera from 23 of these patients were positive for r-HuEpo-neutralizing antibodies, and their bone marrow biopsies indicated pure red-cell aplasia, indicating the loss of erythroblasts. Sera and bone marrow biopsies from the remaining seven patients were negative for anti-r-HuEpo antibodies and red-cell aplasia, respectively. The cause for r-HuEpo hyporesponsiveness was occult gastrointestinal bleeding. Thus, subcutaneous injection of biosimilar r-HuEpo can cause adverse immunological effects. A large, long-term, pharmacovigilance study is necessary to monitor and ensure patient safety for these agents.
authors: Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. kearkiat@hotmail.com
authors: Kearkiat
authors: K
authors: Praditpornsilpa
authors: Khajohn
authors: K
authors: Tiranathanagul
authors: Pawinee
authors: P
authors: Kupatawintu
authors: Saengsuree
authors: S
authors: Jootar
authors: Tanin
authors: T
authors: Intragumtornchai
authors: Kriang
authors: K
authors: Tungsanga
authors: Tanyarat
authors: T
authors: Teerapornlertratt
authors: Dusit
authors: D
authors: Lumlertkul
authors: Natavudh
authors: N
authors: Townamchai
authors: Paweena
authors: P
authors: Susantitaphong
authors: Pisut
authors: P
authors: Katavetin
authors: Talerngsak
authors: T
authors: Kanjanabuch
authors: Yingyos
authors: Y
authors: Avihingsanon
authors: Somchai
authors: S
authors: Eiam-Ong
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000096:biosynthesis*; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011994:Recombinant Proteins; D012010:Red-Cell Aplasia, Pure / Q000139:chemically induced; D012307:Risk Factors; D013785:Thailand
chemical_list: D057134:Antibodies, Neutralizing; D011994:Recombinant Proteins; D004921:Erythropoietin