Report on 4 cases with decreased recovery due to neutralizing antibodies specific for PEGylated recombinant factor VIII.
J Thromb Haemost
; 21(10): 2771-2775, 2023 10.
Article
em En
| MEDLINE
| ID: mdl-37543216
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 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator VIII
/
Hemofilia A
Tipo de estudo:
Diagnostic_studies
Limite:
Adult
/
Humans
Idioma:
En
Revista:
J Thromb Haemost
Ano de publicação:
2023
Tipo de documento:
Article