Biosimilar recombinant human erythropoietin induces the production of neutralizing antibodies
Authors: Hugo H. Ferro, Eliseo B. González
Journal: Kidney International (2012)

To the Editor: We have read with great interest the paper by Praditpornsilpa et al.1.Praditpornsilpa K. Tiranathanagul K. Kupatawintu P. et al.Biosimilar recombinant human erythropoietin induces the production of neutralizing antibodies.Kidney Int. 2011; 80: 88-92Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar and the related comment by Wish2.Wish J.B. Erythropoiesis-stimulating agents and pure red-cell aplasia: you can’t fool Mother Nature.Kidney Int. 2011; 80: 11-13Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar about induction of neutralizing antibodies by biosimilar epoetin products in Thailand. As far as we know, the only Argentine-manufactured epoetin marketed in Thailand is Hemax (Bio Sidus SA, Buenos Aires, Argentina), which is probably the Argentine product mentioned in Praditpornsilpa's report, together with products of other origins. The induction of such antibodies seems to be a class effect of erythropoiesis stimulators and we agree that it is shared by biosimilar and innovator epoetins. This concept emphasizes the importance of a pharmacovigilance plan and risk minimization strategies for epoetin products. However, some statements in both articles can be misleading, including the putative existence of a pure red-cell aplasia (PRCA) epidemic induced by biosimilar epoetins in Thailand and the assumption that no pharmacovigilance is performed for such products. A point estimation of antibodies and aplasia (as in the report by Praditpornsilpa et al.1.Praditpornsilpa K. Tiranathanagul K. Kupatawintu P. et al.Biosimilar recombinant human erythropoietin induces the production of neutralizing antibodies.Kidney Int. 2011; 80: 88-92Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar) does not mean/demonstrate the existence of epidemic PRCA induced by biosimilars, as suggested by Wish.2.Wish J.B. Erythropoiesis-stimulating agents and pure red-cell aplasia: you can’t fool Mother Nature.Kidney Int. 2011; 80: 11-13Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar Hemax was registered in Argentina in 1990, before the biosimilarity concept arose in Europe, and its formulation has remained unchanged. Pharmacovigilance activities on Hemax include antibodies detection since 1998. Hemax has been in the Thai market since 1997 and, upon requirement of the local licensee, since February 2004 (after the outbreak of PRCA associated to an innovator epoetin product and related to formulation changes), we began to receive sera for anti-epoetin testing from a few patients treated with Hemax that reported loss of efficacy. We suspect that the increased rate of requirements for anti-epoetin antibodies from Thailand reflects the increased interest on PRCA triggered by the epidemics associated to Eprex, in a country in which the rate of aplastic anemia is higher than in Western countries,3.Issaragrisil S. Epidemiology of aplastic anemia in Thailand.Int J Hematol. 1999; 70: 137-140PubMed Google Scholar involving probably human leukocyte antigen background. The worldwide rate of PRCA associated to Hemax, estimated in 2007 in 1.21 cases per 100,000 treatment-years,4.Ferro H.H. Donato H. Valtuille R. et al.Worldwide pharmacovigilance of a biosimilar product containing epoetin (Hemax®).in: Drug Safety. 31. 2008: 913Google Scholar seems similar to reports with other epoetins, excluding the already mentioned epidemics induced by Eprex. A prospective study, including data from all epoetin marketed in Thailand, as the one currently under way by the Thai FDA (together with three Thai scientific societies), should provide a more precise assessment of prevalence and association between PRCA and epoetin products.