Product type and the risk of inhibitor development in nonsevere haemophilia A patients: a case-control study

Authors: van Velzen, AS., Eckhardt, CL., Peters, M., Oldenburg, J., Cnossen, M., Liesner, R., Morfini, M., Castaman, G., McRae, S., van der Bom, JG., and Fijnvandraat, K.

Publication: Br.J Haematol.;

Affiliations: Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children’s Hospital, Academic Medical Center, Amsterdam, the Netherlands; Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany; Department of Pediatric Oncology and Hematology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Haematology & Oncology and Children’s Haemophilia Comprehensive Care Centre, Great Ormond Street Children’s Hospital & Institute of Child Health, London, UK; Italian Association of Haemophilia Centres (AICE), Florence, Italy; Department of Oncology, Center for Bleeding Disorders, Careggi University Hospital, Firenze, Italy; Department of Haematology, Royal Adelaide Hospital, Adelaide, Australia; Sanquin Research and Department of Clinical Epidemiology, Center for Clinical Transfusion Research, Leiden University Medical Center, Leiden, the Netherlands

Abstract: Inhibitor development is a major complication of treatment with factor VIII concentrates in nonsevere haemophilia A. It has been suggested that plasma-derived factor VIII (FVIII) concentrates elicit fewer inhibitors than recombinant FVIII concentrates, but studies in severe haemophilia A patients have shown conflicting results. We designed a case-control study to investigate the clinical and genetic risk factors for inhibitor development in nonsevere haemophilia A patients. We investigated whether the type of FVIII concentrate was associated with inhibitor development in nonsevere haemophilia A patients. This nested case-control study includes 75 inhibitor patients and 223 controls, from a source population of the INSIGHT study, including all nonsevere haemophilia A patients (FVIII:C 2-40%) that were treated with FVIII concentrates in 33 European and one Australian centre. Cases and controls were matched for date of birth and cumulative number of exposure days (CED) to FVIII concentrate. A conditional logistic regression model was used to calculate unadjusted and adjusted odds ratios. No increased risk for inhibitor development was found for any type of FVIII concentrate; either when comparing recombinant FVIII concentrates to plasma-derived FVIII concentrates (adjusted odds ratio 0·96, 95% confidence interval (CI) 0·36-2·52) or for specific types of FVIII concentrates.