Recombinant human erythropoietin (epoetin) is one of the success stories of modern medicine. Erythropoietin is essential for the production of red blood cells (erythrocytes), and epoetin is used in the treatment of patients in whom production of the hormone erythropoietin is impaired, such as those with chronic renal failure. Epoetin is one of the world's best-selling drugs, with over US $2.5bn sales recorded each year. Its selectivity for receptors that are expressed only on erythrocyte progenitor cells gives the drug an enviable degree of specificity, and its therapeutic index is among the highest known. The report in a recent issue of the New England Journal of Medicine of a collection of the first serious adverse events to be associated with the medically directed use of epoetin is therefore a surprising cloud to appear on the horizon.

Epoetin has had an almost blameless record, with the only substantial adverse effects being reported so far in athletes who had taken the drug illicitly, in the hope of increasing their red-cell count — so-called 'blood doping'. The consequent rise in blood viscosity has led to several cases of fatal thromboembolism. But Casadevall et al. now describe 13 patients receiving epoetin as standard treatment for chronic renal failure who developed severe anaemia, which could be treated only by blood transfusion. In all cases, this anaemia was caused by the production of antibodies to erythropoietin, which neutralize both epoetin and any remaining endogenous erythropoietin.

What drives the immune response in this subgroup of patients is unclear. Interestingly, these 13 cases — plus another 30 or so incidences of anaemia that have arisen recently — have almost all occurred in Europe since 1998, and might possibly be the result of some change to the product formulation. Although the numbers affected might seem insignificant when compared with the 3 million patients who are treated with epoetin each year, the relatively sudden appearance of a serious adverse effect for a tried-and-tested product reminds us that much remains to be discovered about the immunogenicity of biopharmaceuticals.