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Recombinant factor VIII products and inhibitor development in previously untreated patients with severe haemophilia A : Combined analysis of three studies

Volkers, Peter; Hanschmann, Kay-Martin; Calvez, Thierry; Chambost, Hervé; Collins, Peter W; Demiguel, Virginie; Hart, Daniel P; Hay, Charles R M; Goudemand, Jenny and Ljung, Rolf LU , et al. (2019) In Haemophilia 25(3). p.398-407
Abstract

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... (More)

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.

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publication status
published
subject
keywords
antibodies, blood coagulation disorders, blood coagulation factor inhibitors, factor VIII, haemophilia A, neutralizing, recombinant factor VIII products
in
Haemophilia
volume
25
issue
3
pages
398 - 407
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • scopus:85065498351
ISSN
1351-8216
DOI
10.1111/hae.13747
language
English
LU publication?
yes
id
1937f55a-e354-48f9-87bd-abf14b8c48b4
date added to LUP
2019-05-13 16:35:43
date last changed
2019-06-11 04:04:23
@article{1937f55a-e354-48f9-87bd-abf14b8c48b4,
  abstract     = {<p>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.</p><p>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).</p><p>METHODS: We conducted a combined analysis of individual patient data from three large studies in previously untreated patients (PUPs) with severe haemophilia A.</p><p>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.</p><p>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.</p>},
  author       = {Volkers, Peter and Hanschmann, Kay-Martin and Calvez, Thierry and Chambost, Hervé and Collins, Peter W and Demiguel, Virginie and Hart, Daniel P and Hay, Charles R M and Goudemand, Jenny and Ljung, Rolf and Palmer, Ben P and Santagostino, Elena and van Hardeveld, Ella M and van den Berg, Marijke and Keller-Stanislawski, Brigitte},
  issn         = {1351-8216},
  keyword      = {antibodies,blood coagulation disorders,blood coagulation factor inhibitors,factor VIII,haemophilia A,neutralizing,recombinant factor VIII products},
  language     = {eng},
  number       = {3},
  pages        = {398--407},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Haemophilia},
  title        = {Recombinant factor VIII products and inhibitor development in previously untreated patients with severe haemophilia A : Combined analysis of three studies},
  url          = {http://dx.doi.org/10.1111/hae.13747},
  volume       = {25},
  year         = {2019},
}