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Inhibitor development and FVIII gene mutation analysis in a pediatric cohort treated with sucrose formulated, full‐length recombinant Factor VIII
Author(s) -
Kreuz W.,
Leissinger C,
Oldenburg J,
Lusher J,
Kelleher J,
Gorina E,
Kellermann E,
Larson P
Publication year - 2002
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1046/j.1365-2516.2002.d01-2_4.x
Subject(s) - medicine , recombinant dna , titer , incidence (geometry) , cohort , gastroenterology , prospective cohort study , immunology , antibody , gene , biochemistry , chemistry , physics , optics
Treatment of previously untreated patients (PUPs) and minimally treated patients (MTPs) with severe hemophilia A using FVIII concentrates is complicated by FVIII inhibitor formation in ∼30% of patients. The incidence of FVIII inhibitors was determined in a prospective clinical trial of sucrose‐formulated full‐length recombinant FVIII (rFVIII‐FS, KOGENATE ® Bayer; Kogenate ® FS) in pediatric patients. Methods: PUPs and MTPs (=4 exposure days‐EDs) with hemophilia A (<2% FVIII) were enrolled from 19 EU and 13 US centers. Sixty patients were evaluable for inhibitor formation (EU, 31; US, 29). Patients were tested regularly with the Nijmegen‐modified Bethesda assay (negative, ≤0.6 BU; Low Titer, >0.6‐5 BU; High Titer, >5 BU). Results: In the EU cohort (31 Caucasian), 4 patients developed inhibitors (3 Low; 1 High). Five high titer inhibitors developed in the US cohort (17 Caucasian; 5 Black; 7 Other). Median EDs at inhibitor detection was 8 [range, 3‐16], and at study end 1 EU and 4 US patients had <20 EDs. The incidence of inhibitors in patients achieving 20 ED was 16.4% (9/55). Conclusions: The rate of inhibitor formation in pediatric patients with severe hemophilia A treated with rFVIII‐FS is consistent with that observed with plasma‐derived and other recombinant FVIII products. Major gene disruptions were observed in all inhibitor patients.