Epoetin treatment may evoke antibody response, leading to pure red-cell aplasia

מתוך medicontext.co.il
NEW YORK (Reuters Health) – In patients with chronic renal failure treated with recombinant human erythropoietin, the formation of neutralizing antierythropoietin antibodies can result in the development of pure red-cell aplasia, European investigators report in The New England Journal of Medicine for February 14.

Dr. Nicole Casadevall, of the Hopital Hotel-Dieu in Paris, and colleagues identified 13 chronic dialysis patients who developed severe transfusion-dependent anemia between 1998 and 2000 following an initial hematologic response to epoetin. The diagnosis of red-cell aplasia was based on the absence of erythroid cells in bone marrow or of circulating reticulocytes.

Twelve of the patients had been treated with epoetin-alpha and one with epoetin-beta. The severe anemia developed after 3 to 67 months of treatment.

After epoetin treatment was discontinued, six patients recovered some erythropoietic function of their own after being treated with immunosuppressants or a renal allograft. Three remain dependent on transfusions more than 2 years later. The remaining four patients also still require transfusions, but their followup has been too short to determine their clinical course.

Tests of the patients' serum demonstrated neutralizing antibodies with a high affinity and specificity for the protein moiety of epoetin and for native erythropoietin, Dr. Casadevall and her colleagues report. After treatment was discontinued, the antibody titers slowly decreased.

In an accompanying editorial, Dr. H. Franklin Bunn, of Brigham and Women's Hospital in Boston, points out that at least 25 other patients in Europe have developed the same complication during the same time period. This immune response is the only serious adverse effect of the recombinant human protein to have occurred when it was administered under appropriate medical supervision, he notes.

"This state of affairs raises the question whether the antigenicity of the European product has been slightly enhanced by a change in the manufacturing process that has altered either the formulation or the carbohydrate structure of epoetin," Dr. Bunn suggests.

This possibility is of concern, he adds, because a new preparation of epoetin, darbepoetin-alfa, has been developed by adding new glycosylation sites, for the purpose of prolonging its half-life. It may be that this new preparation will also engender cross-reacting antibodies, he warns.

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