Report on 4 cases with decreased recovery due to neutralizing antibodies specific for PEGylated recombinant factor VIII
(2023) In Journal of Thrombosis and Haemostasis 21(10). p.2771-2775- Abstract
Background: The immunogenicity, safety, and efficacy of recombinant factor VIII (rFVIII) have gained increasing interest after the introduction of extended half-life products with various modifications of the rFVIII molecule, such as covalent attachment of polyethylene glycol (PEG). Anti-PEG antibodies may be associated with a temporary reduction of FVIII recovery, but according to previous studies, they usually disappear after continuous dosing. Anti-PEG antibodies with an inhibitory capacity have never been demonstrated in patients treated with PEGylated rFVIII products. Objectives: To routinely switch from standard half-life to PEGylated extended half-life rFVIII products in patients with hemophilia A. Methods: From December 2022... (More)
Background: The immunogenicity, safety, and efficacy of recombinant factor VIII (rFVIII) have gained increasing interest after the introduction of extended half-life products with various modifications of the rFVIII molecule, such as covalent attachment of polyethylene glycol (PEG). Anti-PEG antibodies may be associated with a temporary reduction of FVIII recovery, but according to previous studies, they usually disappear after continuous dosing. Anti-PEG antibodies with an inhibitory capacity have never been demonstrated in patients treated with PEGylated rFVIII products. Objectives: To routinely switch from standard half-life to PEGylated extended half-life rFVIII products in patients with hemophilia A. Methods: From December 2022 until May 2023, 83 adults with hemophilia A attending Oslo Haemophilia Comprehensive Care Centre received a test dose with a PEGylated rFVIII product to switch treatment. Four patients presented with decreased recovery without the presence of an FVIII inhibitor. Accordingly, we performed a variant inhibitor test utilizing different rFVIII concentrates as a source of FVIII and enzyme-linked immunosorbent assay to search for anti-PEG antibodies. Results: We found inhibitory anti-PEG/anti-PEGylated rFVIII antibodies in 4 patients (5%), both persistent and transient, explaining the impaired recovery. The patients had neutralizing anti-PEG antibodies prior to the first dosing of PEGylated rFVIII. We demonstrated neutralizing antibodies (mainly immunoglobuline G) specific for PEG and all 3 commercially available PEGylated rFVIII products. Conclusion: The number of patients with inhibitory anti-PEG antibodies was significant, and the presence of inhibitors against PEGylated rFVIII emphasizes the importance of individual monitoring when switching FVIII concentrates to ensure safety and efficacy of the treatment.
(Less)
- author
- Hillarp, Andreas LU ; Holme, Pål A. ; Wåland, Erik P. ; Le, Marie S. ; Henriksson, Carola E. ; Tjønnfjord, Geir E. and Måseide, Ragnhild J.
- organization
- publishing date
- 2023-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- extended half-life FVIII products, FVIII recovery, hemophilia A, neutralizing anti-PEG antibodies, PEGylated recombinant FVIII products
- in
- Journal of Thrombosis and Haemostasis
- volume
- 21
- issue
- 10
- pages
- 5 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:85169051473
- pmid:37543216
- ISSN
- 1538-7933
- DOI
- 10.1016/j.jtha.2023.07.019
- language
- English
- LU publication?
- yes
- id
- dd3fb0d2-0ea4-4b29-bea8-a41354b06a7c
- date added to LUP
- 2023-11-30 13:42:27
- date last changed
- 2024-04-27 16:41:17
@article{dd3fb0d2-0ea4-4b29-bea8-a41354b06a7c,
abstract = {{<p>Background: The immunogenicity, safety, and efficacy of recombinant factor VIII (rFVIII) have gained increasing interest after the introduction of extended half-life products with various modifications of the rFVIII molecule, such as covalent attachment of polyethylene glycol (PEG). Anti-PEG antibodies may be associated with a temporary reduction of FVIII recovery, but according to previous studies, they usually disappear after continuous dosing. Anti-PEG antibodies with an inhibitory capacity have never been demonstrated in patients treated with PEGylated rFVIII products. Objectives: To routinely switch from standard half-life to PEGylated extended half-life rFVIII products in patients with hemophilia A. Methods: From December 2022 until May 2023, 83 adults with hemophilia A attending Oslo Haemophilia Comprehensive Care Centre received a test dose with a PEGylated rFVIII product to switch treatment. Four patients presented with decreased recovery without the presence of an FVIII inhibitor. Accordingly, we performed a variant inhibitor test utilizing different rFVIII concentrates as a source of FVIII and enzyme-linked immunosorbent assay to search for anti-PEG antibodies. Results: We found inhibitory anti-PEG/anti-PEGylated rFVIII antibodies in 4 patients (5%), both persistent and transient, explaining the impaired recovery. The patients had neutralizing anti-PEG antibodies prior to the first dosing of PEGylated rFVIII. We demonstrated neutralizing antibodies (mainly immunoglobuline G) specific for PEG and all 3 commercially available PEGylated rFVIII products. Conclusion: The number of patients with inhibitory anti-PEG antibodies was significant, and the presence of inhibitors against PEGylated rFVIII emphasizes the importance of individual monitoring when switching FVIII concentrates to ensure safety and efficacy of the treatment.</p>}},
author = {{Hillarp, Andreas and Holme, Pål A. and Wåland, Erik P. and Le, Marie S. and Henriksson, Carola E. and Tjønnfjord, Geir E. and Måseide, Ragnhild J.}},
issn = {{1538-7933}},
keywords = {{extended half-life FVIII products; FVIII recovery; hemophilia A; neutralizing anti-PEG antibodies; PEGylated recombinant FVIII products}},
language = {{eng}},
number = {{10}},
pages = {{2771--2775}},
publisher = {{Wiley-Blackwell}},
series = {{Journal of Thrombosis and Haemostasis}},
title = {{Report on 4 cases with decreased recovery due to neutralizing antibodies specific for PEGylated recombinant factor VIII}},
url = {{http://dx.doi.org/10.1016/j.jtha.2023.07.019}},
doi = {{10.1016/j.jtha.2023.07.019}},
volume = {{21}},
year = {{2023}},
}