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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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 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.

Detaljer

Författare
  • Peter Volkers
  • Kay-Martin Hanschmann
  • Thierry Calvez
  • Hervé Chambost
  • Peter W Collins
  • Virginie Demiguel
  • Daniel P Hart
  • Charles R M Hay
  • Jenny Goudemand
  • Rolf Ljung
  • Ben P Palmer
  • Elena Santagostino
  • Ella M van Hardeveld
  • Marijke van den Berg
  • Brigitte Keller-Stanislawski
Enheter & grupper
Externa organisationer
  • University Hospital of Wales
  • University of Manchester
  • The United Kingdom National Haemophilia Database, Manchester, UK.
  • Maggiore Hospital Policlinico
  • Paul Ehrlich Institute
  • Paris-Sorbonne University
  • Aix-Marseille University
  • Santé Publique France
  • Royal London School of Medicine and Dentistry
  • PedNet Haemophilia Registry
  • Lille University Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Hematologi
  • Kardiologi

Nyckelord

Originalspråkengelska
Sidor (från-till)398-407
TidskriftHaemophilia
Volym25
Utgivningsnummer3
Tidigt onlinedatum2019
StatusPublished - 2019
PublikationskategoriForskning
Peer review utfördJa