Short term efficacy of recombinant porcine factor VIII in patients with factor VIII inhibitors.
Adult
Aged
Animals
Autoantibodies
/ immunology
Blood Coagulation Tests
/ methods
Factor VIII
/ antagonists & inhibitors
Female
Hemophilia A
/ genetics
Hemorrhage
/ prevention & control
Humans
Infusions, Intravenous
Male
Recombinant Proteins
/ administration & dosage
Retrospective Studies
Safety
Swine
Treatment Outcome
FVIII inhibitors
Obizur
acquired haemophilia
recombinant porcine FVIII
Journal
Haemophilia : the official journal of the World Federation of Hemophilia
ISSN: 1365-2516
Titre abrégé: Haemophilia
Pays: England
ID NLM: 9442916
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
18
11
2019
revised:
30
03
2020
accepted:
07
04
2020
pubmed:
28
4
2020
medline:
20
5
2021
entrez:
28
4
2020
Statut:
ppublish
Résumé
Antibodies against factor VIII (FVIII), seen in acquired (AHA) and congenital haemophilia A, lead to severe bleeding diatheses. Current first-line treatment includes bypass agents. Recombinant porcine sequence FVIII (rpFVIII) was developed as an alternative therapy. To describe our institutional experience with the use of rpFVIII. A retrospective chart review of five patients treated with rpVIII between 2016 and 2019. Five patients (four AHA, one congenital haemophilia with inhibitors) were treated with rpFVIII. No patient had an adverse event during infusion. All patients initially exhibited a response evidenced by increased FVIII levels from baseline <1% to 81%-170%, normalization of the activated partial thromboplastin time (aPTT) and resolution of bleeding. However, all five patients were subsequently noted to have decreasing peak FVIII levels and aPTT prolongation, either within the initial treatment course or upon later re-administration. Resistance to rpFVIII was recognized after an average of 12.4 exposure days. Porcine FVIII inhibitor levels measured afterwards were present (detectable-170 Bethesda units) in all patients. Three out of four AHA subjects also developed an increase in the anti-human FVIII inhibitor titres after receiving rpFVIII. rpFVIII was safe and initially effective in all patients. However, its use is associated with development of an inhibitor to rpFVIII, decreasing its efficacy and duration of effect. Further, rpFVIII use may lead to an increase in patient anti-human FVIII inhibitor titres. A larger study is necessary to appropriately assess the incidence of these outcomes.
Sections du résumé
BACKGROUND
BACKGROUND
Antibodies against factor VIII (FVIII), seen in acquired (AHA) and congenital haemophilia A, lead to severe bleeding diatheses. Current first-line treatment includes bypass agents. Recombinant porcine sequence FVIII (rpFVIII) was developed as an alternative therapy.
AIM
OBJECTIVE
To describe our institutional experience with the use of rpFVIII.
METHODS
METHODS
A retrospective chart review of five patients treated with rpVIII between 2016 and 2019.
RESULTS
RESULTS
Five patients (four AHA, one congenital haemophilia with inhibitors) were treated with rpFVIII. No patient had an adverse event during infusion. All patients initially exhibited a response evidenced by increased FVIII levels from baseline <1% to 81%-170%, normalization of the activated partial thromboplastin time (aPTT) and resolution of bleeding. However, all five patients were subsequently noted to have decreasing peak FVIII levels and aPTT prolongation, either within the initial treatment course or upon later re-administration. Resistance to rpFVIII was recognized after an average of 12.4 exposure days. Porcine FVIII inhibitor levels measured afterwards were present (detectable-170 Bethesda units) in all patients. Three out of four AHA subjects also developed an increase in the anti-human FVIII inhibitor titres after receiving rpFVIII.
CONCLUSION
CONCLUSIONS
rpFVIII was safe and initially effective in all patients. However, its use is associated with development of an inhibitor to rpFVIII, decreasing its efficacy and duration of effect. Further, rpFVIII use may lead to an increase in patient anti-human FVIII inhibitor titres. A larger study is necessary to appropriately assess the incidence of these outcomes.
Substances chimiques
Autoantibodies
0
Recombinant Proteins
0
F8 protein, human
839MOZ74GK
Factor VIII
9001-27-8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
601-606Informations de copyright
© 2020 John Wiley & Sons Ltd.
Références
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