Inhibitor development in previously untreated patients with hemophilia A: a prospective long-term follow-up comparing plasma-derived and recombinant products.

Abstract	In order to assess inhibitor development in previously untreated patients (PUPs) with severe (factor VIII [FVIII]<1%) and moderate (FVIII 1 to 5%) hemophilia A, a prospective study was initiated in 1976. During the 23-year study period, 72 hemophiliacs were frequently exposed prophylactically or on demand to plasma-derived (pd) (n = 51) or recombinant FVIII (rFVIII) (n = 21) concentrates (median 270 exposure days [ED]). Inhibitor testing was performed before the first exposure and at regular intervals thereafter. Of the 72 hemophilia A patients, 22 (32%) developed an inhibitor after 15 ED in median (range 4 to 195); 17 (77%) were high responders (>5 Bethesda Units [BU]), and the remaining 5 patients (23%) were low responders (>0.6 to 5 BU). The severely affected patients (n = 46) showed a significantly higher frequency of inhibitor formation (43%) than did the moderate ones (8%). Comparing the severely affected patients receiving pd products exclusively (n = 35) with those treated with recombinant concentrate (n = 11), 37% of the pd group developed a high-titer inhibitor (>5 BU, median 290 ED in noninhibitor patients) and 36% of the recombinant group (median 49 ED in the noninhibitor patients). However, the exposure status of the recombinant noninhibitor patients is rather low and therefore remains a high risk of developing further inhibitors in the future. The mutation type profile revealed no difference between the pd- and the recombinant-treated patients.
Authors	Wolfhart Kreuz, Carmen Escuriola Ettingshausen, Alex Zyschka, Johannes Oldenburg, Inmaculada Martinez Saguer, Silke Ehrenforth, Thomas Klingebiel
Journal	Seminars in thrombosis and hemostasis (Semin Thromb Hemost) Vol. 28 Issue 3 Pg. 285-90 (Jun 2002) ISSN: 0094-6176 [Print] United States
PMID	12098090 (Publication Type: Journal Article)
Chemical References	Autoantibodies Recombinant Proteins F8 protein, human Factor VIII
Topics	Autoantibodies (blood) Cohort Studies Factor VIII (administration & dosage, immunology) Follow-Up Studies Hemophilia A (drug therapy, genetics, immunology) Hemophilia B (drug therapy, genetics, immunology) Humans Mutation Prospective Studies Recombinant Proteins (immunology) Risk Time Factors

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