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Inhibitor development according to FVIII concentrates in previously untreated patients with severe hemophilia A : update from the PedNet registry

Fischer, K. ; Olivieri, M. ; Ranta, Susanna ; Pinto, Fernando ; Labarque, V. ; Zápotocká, E. ; Motwani, J. ; Kenet, Gili ; Königs, Christoph and Nolan, Beatrice , et al. (2026) In Journal of Thrombosis and Haemostasis
Abstract

Background Treatment of severe hemophilia A (SHA) with FVIII concentrates is complicated by the development of neutralizing inhibitors in about 30% during the first 50 exposure days (EDs). Despite extensive research, inhibitor risk of different FVIII concentrates remains to be elucidated. Objectives This study aimed to analyze inhibitor development according to (classes of) individual FVIII concentrates in previously untreated patients (PUPs) with SHA. Methods PUPs with SHA born between 2000 and 2024 were followed until inhibitor development or 50 EDs. Inhibitor development according to classes of FVIII concentrates (ie, plasma-derived [pdFVIII] vs recombinant [rFVIII] and standard vs extended half-life [SHL-rFVIII vs EHL-rFVIII]) and... (More)

Background Treatment of severe hemophilia A (SHA) with FVIII concentrates is complicated by the development of neutralizing inhibitors in about 30% during the first 50 exposure days (EDs). Despite extensive research, inhibitor risk of different FVIII concentrates remains to be elucidated. Objectives This study aimed to analyze inhibitor development according to (classes of) individual FVIII concentrates in previously untreated patients (PUPs) with SHA. Methods PUPs with SHA born between 2000 and 2024 were followed until inhibitor development or 50 EDs. Inhibitor development according to classes of FVIII concentrates (ie, plasma-derived [pdFVIII] vs recombinant [rFVIII] and standard vs extended half-life [SHL-rFVIII vs EHL-rFVIII]) and individual concentrates used by ≥40 PUPs were compared using multivariable Cox regression (generating rate ratios [RR] with 95% CIs). Results One thousand five hundred three PUPs were included. Inhibitors developed in 444 PUPs after a median of 12 EDs (cumulative incidence, 31.0%; CI, 28.6%-33.4%). Compared to SHL-rFVIII, inhibitor risk was similar for pdFVIII (RR, 0.89; CI, 0.69-1.14) and EHL-rFVIII (RR, 1.10; CI, 0.75-1.61). Nine individual FVIII concentrates (5 SHL-rFVIII, 1 EHL-rFVIII, and 3 pdFVIII) were compare to Advate ( n = 392): only KogenateFS/HelixateNexGen ( n = 307; RR, 1.40; CI, 1.07-1.82, P , .013) and Fanhdi ( n = 50; RR, 1.72; CI, 1.11-2.68; P , .024) showed increased inhibitor risk. Conclusion Inhibitor development occurred in 31.0% of PUPs, with similar incidence across SHL-rFVIII, EHL-rFVIII, and pdFVIII. Analysis of individual concentrates showed increased inhibitor risk for Kogenate FS/Helixate NexGen (SHL-rFVIII) and for the first time for Fanhdi (pdFVIII). In the absence of formal PUP studies, PedNet will continue evaluating the inhibitor risk according to individual FVIII concentrates.

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Contribution to journal
publication status
epub
subject
keywords
antibodies, neutralizing, factor VIII, hemophilia A, previously untreated patients (PUPs), registries
in
Journal of Thrombosis and Haemostasis
publisher
Elsevier
external identifiers
  • pmid:42119947
  • scopus:105040557111
ISSN
1538-7933
DOI
10.1016/j.jtha.2026.04.031
language
English
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yes
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Publisher Copyright: © 2026 International Society on Thrombosis and Haemostasis.
id
9851a8a0-247c-43cf-bef5-e60761f46feb
date added to LUP
2026-06-11 09:34:20
date last changed
2026-09-04 22:16:24
@article{9851a8a0-247c-43cf-bef5-e60761f46feb,
  abstract     = {{<p>Background Treatment of severe hemophilia A (SHA) with FVIII concentrates is complicated by the development of neutralizing inhibitors in about 30% during the first 50 exposure days (EDs). Despite extensive research, inhibitor risk of different FVIII concentrates remains to be elucidated. Objectives This study aimed to analyze inhibitor development according to (classes of) individual FVIII concentrates in previously untreated patients (PUPs) with SHA. Methods PUPs with SHA born between 2000 and 2024 were followed until inhibitor development or 50 EDs. Inhibitor development according to classes of FVIII concentrates (ie, plasma-derived [pdFVIII] vs recombinant [rFVIII] and standard vs extended half-life [SHL-rFVIII vs EHL-rFVIII]) and individual concentrates used by ≥40 PUPs were compared using multivariable Cox regression (generating rate ratios [RR] with 95% CIs). Results One thousand five hundred three PUPs were included. Inhibitors developed in 444 PUPs after a median of 12 EDs (cumulative incidence, 31.0%; CI, 28.6%-33.4%). Compared to SHL-rFVIII, inhibitor risk was similar for pdFVIII (RR, 0.89; CI, 0.69-1.14) and EHL-rFVIII (RR, 1.10; CI, 0.75-1.61). Nine individual FVIII concentrates (5 SHL-rFVIII, 1 EHL-rFVIII, and 3 pdFVIII) were compare to Advate ( n = 392): only KogenateFS/HelixateNexGen ( n = 307; RR, 1.40; CI, 1.07-1.82, P , .013) and Fanhdi ( n = 50; RR, 1.72; CI, 1.11-2.68; P , .024) showed increased inhibitor risk. Conclusion Inhibitor development occurred in 31.0% of PUPs, with similar incidence across SHL-rFVIII, EHL-rFVIII, and pdFVIII. Analysis of individual concentrates showed increased inhibitor risk for Kogenate FS/Helixate NexGen (SHL-rFVIII) and for the first time for Fanhdi (pdFVIII). In the absence of formal PUP studies, PedNet will continue evaluating the inhibitor risk according to individual FVIII concentrates.</p>}},
  author       = {{Fischer, K. and Olivieri, M. and Ranta, Susanna and Pinto, Fernando and Labarque, V. and Zápotocká, E. and Motwani, J. and Kenet, Gili and Königs, Christoph and Nolan, Beatrice and Blatný, J. and Carcao, Manuel and Van Geet, C. and de Kovel, Marloes and Andersson, Nadine G.}},
  issn         = {{1538-7933}},
  keywords     = {{antibodies, neutralizing; factor VIII; hemophilia A; previously untreated patients (PUPs); registries}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Thrombosis and Haemostasis}},
  title        = {{Inhibitor development according to FVIII concentrates in previously untreated patients with severe hemophilia A : update from the PedNet registry}},
  url          = {{http://dx.doi.org/10.1016/j.jtha.2026.04.031}},
  doi          = {{10.1016/j.jtha.2026.04.031}},
  year         = {{2026}},
}