Abstract
Previously treated patients (PTP), who have not developed an inhibitor (inh.) so far, are considered to be tolerant to factor VIII and at low risk for inh. development. Therefore inh. detection in a PTP should raise concerns about the concomitant variables such as product neo-antigenicity or way of application.
To find out about the current situation regarding inh. development in PTP in Germany, we conduct a retrospective study. A questionnaire was sent to 87 haemophilia treating centers, so far 46 of them answered. 28 PTP-inh. developments during the last 5 years were reported. Age of the patient (median 35), severity of haemophilia A (18 severe, 2 moderate, 8 mild), exposuer days (median 30) and gene mutation (intron-22-inversions 31%, large deletions 13%, missense mutations 25%, stop mutation 6%, small deletion 13%) were recorded. 8 different factor VIII concentrates were given during inh. development (5 plasma derived, 3 recombinant). Way of application (16 times bolus infusion, 3 times continuous infusion, 5 times both), former change of product, infused amount until inh. development, inh. characteristic, concomitant diseases and medication were registered.
In conclusion most of the patients were over 18 years old (17/28) when the inh. developed. Most of them had severe haemophilia A (18/28) and had at least one change of product before inh. detection. Our data are still too small to draw any conclusion concerning product neo-antigenicity or treatment modalities. Nevertheless it became obvious that inh. development in PTP is still a serious and underestimated problem in haemophilia treatment today. Secondly data showed that there is a variety of PTP definitions in Germany, referring to age of pat, number of exposure days and former change of product. An international definition for PTP would be helpful. A national haemophilia register would make it easier to evaluate data in the future and a prospective, not product related study should be conducted.
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