Recombinant factor VIII products and inhibitor development in previously untreated patients with severe haemophilia A: Combined analysis of three studies.
View/ Open
Published version
Embargoed until: 5555-01-01
Embargoed until: 5555-01-01
Volume
25
Pagination
398 - 407
Publisher
DOI
10.1111/hae.13747
Journal
Haemophilia
Issue
ISSN
1351-8216
Metadata
Show full item recordAbstract
INTRODUCTION: Standard treatment of congenital haemophilia A is based on replacement therapy with coagulation factor VIII (FVIII) products. A major complication of FVIII therapy is the occurrence of IgG alloantibodies (inhibitors) that neutralize FVIII activity. AIM: The aim of the analysis was estimating the risk of high-titre inhibitor associated with the second-generation full-length product compared to third-generation full-length product and other recombinant FVIII (rFVIII). METHODS: We conducted a combined analysis of individual patient data from three large studies in previously untreated patients (PUPs) with severe haemophilia A. RESULTS: A total of 1109 PUPs were treated from 1993 to 2013 including 787 PUPs treated from 2004 onwards (primary analysis cohort). A total of 322 patients (29.0%) developed an inhibitor, of which 192 (17.3%) a high-titre inhibitor. In the primary analysis set, 29.9% of patients developed an inhibitor and 17.2% a high-titre inhibitor. The combined analysis indicated a lower risk of high-titre inhibitor development for the third-generation rFVIII product compared to the second-generation rFVIII product (primary analysis: adjusted hazard ratio (HR) = 0.72, 95% CI: 0.49 to 1.06). Adjusted HR for all inhibitor development was significantly lower for the third-generation product compared to the second-generation product. CONCLUSION: The trend of an increased risk of inhibitor development in PUPs for one recombinant product illustrates that extrapolation from one recombinant factor VIII product to other products might not be justified.
Authors
Volkers, P; Hanschmann, K-M; Calvez, T; Chambost, H; Collins, PW; Demiguel, V; Hart, DP; Hay, CRM; Goudemand, J; Ljung, RCollections
- Centre for Immunobiology [1097]
Language
Copyright statements
Related items
Showing items related by title, author, creator and subject.
-
Interaction of lifestyle, behaviour or systemic diseases with dental caries and periodontal diseases: consensus report of group 2 of the joint EFP/ORCA workshop on the boundaries between caries and periodontal diseases
Chapple, ILC; Bouchard, P; Cagetti, MG; Campus, G; Carra, M-C; Cocco, F; Nibali, L; Hujoel, P; Laine, ML; Lingstrom, P (2017-03) -
Peptide gene expression in gastrointestinal mucosal ulceration: ordered sequence or redundancy?
Wong, WM; Playford, RJ; Wright, NA (2000-02) -
WS04: Haemophilia: Recent History of Clinical Management (10-Feb1998)
History of Twentieth Century Medicine Group; History of Modern Biomedicine Research Group (22/05/2017)Selection of photos taken at the Witness Seminar “Haemophilia: Recent History of Clinical Management” held by the History of Twentieth Century Medicine Group, 10-Feb-1998. Participants: Dr Derek Bangham, Dr Ethel Bidwell, ...