FREQUENCY OF INHIBITOR DEVELOPMENT IN HEMOPHILIACS TREATED WITH LOW-PURITY FACTOR-VIII

Clinical studies evaluating highly purified monoclonal-antibody-derive d and recombinant-DNA-derived clotting factor concentrates in previous ly untreated (PUPS) severe factor VIII (FVIII) deficient haemophilia p atients, have documented an increased frequency of inhibitors compared with that seen in patients who have received less pure products. Howe ver, a valid comparison of inhibitor frequency in patients treated wit h pure and less pure products has not been possible because appropriat e studies have not been done in PUPS treated with the less pure produc ts. To determine the frequency of inhibitor development in PUPS treate d solely with less pure plasma-derived products (specific activities < 5 FVIII U/mg protein), we reviewed the records of all haemophilia pati ents born between 1975 and 1985 and treated with such products at any of seven centres. 89 patients with severe FVIII deficiency (< 1%) were observed and tested for inhibitors from birth to 5 years old or until 30 bleeding episodes had been treated. 25 of the 89 patients develope d inhibitors (28%), and 21 of these 25 were high-titre responders (> 5 Bethesda units). This frequency of inhibitor development is greater t han that reported in patients treated with monoclonal FVIII products, but the latter patients may not have been followed as long as the pati ents in our report. Our data may make possible a meaningful comparison with the frequency of inhibitor development in PUPS treated solely wi th recombinant-DNA-derived FVIII.