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Multicenter Study
. 2020 Jun;189(6):1182-1191.
doi: 10.1111/bjh.16490. Epub 2020 Mar 22.

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

Alice S van Velzen  1 , Corien L Eckhardt  1 , Marjolein Peters  1 , Johannes Oldenburg  2 , Marjon Cnossen  3 , Ri Liesner  4 , Massimo Morfini  5 , Giancarlo Castaman  6 , Simon McRae  7 , Johanna G van der Bom  8 , Karin Fijnvandraat  1 ; INSIGHT consortium
Affiliations
Multicenter Study

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

Alice S van Velzen et al. Br J Haematol. 2020 Jun.

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.

Keywords: antibodies; factor VIII; haemophilia; risk factors.

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Conflict of interest statement

A.S.V. has given lectures at educational symposiums organised by Novo Nordisk, Baxter and Pfizer and has received unrestricted research funding from CSL Behring. C.L.E. has received an unrestricted grant from The Netherlands Organisation for Health Research and Development (ZonMW) and has given lectures at educational symposiums organised by Novo Nordisk and Baxter. G.C. participated in Advisory boards for Bayer, Shire, Sobi, Pfizer, CSL Behring, Novo Nordisk, Kedrion. J.G.B. has received payment for consultancy meetings with Bayer and Wyeth, has received grants from Bayer Schering Pharma, Baxter, CSL Behring, Novo Nordisk and Wyeth and has received payment for lectures from Bayer. K.F. is a member of the European Hemophilia Treatment and Standardization Board sponsored by Baxter, has received unrestricted research grants from CSL Behring, Pfizer and Bayer, and has given lectures at educational symposiums organised by Pfizer, Baxter and Bayer. The remaining authors declare no competing financial interests.

Figures

Figure 1
Figure 1
Inclusion of patients for case–control study from INSIGHT cohort.
See this image and copyright information in PMC

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