Antibody response to recombinant human coagulation factor VIII in a new rat model of severe hemophilia A

Journal of Thrombosis and Haemostasis : JTH
K M LövgrenB Wiinberg

Abstract

Neutralizing antibodies toward FVIII replacement therapy (inhibitors) are the most serious treatment-related complication in hemophilia A (HA). A rat model of severe HA (F8(-/-) ) has recently been developed, but an immunological characterization is needed to determine the value of using the model for research into inhibitor development. Characterize the antibody response towards recombinant human coagulation factor VIII (rhFVIII) in the HA rat, following a human prophylactic dosing regimen. Two identical studies were performed, which included a total of 17 homozygous HA rats (F8(-/-) , 0% FVIII activity), 12 heterozygous rats (F8(+/-) ), and 12 wild-type (F8(+/+) ) rats. All rats received intravenous injections of rhFVIII at 50 IU kg(-1) twice weekly for 4 weeks. Predosing blood samples were analyzed for binding and neutralizing anti-rhFVIII antibodies at weeks 1-7. In both studies, antibodies developed after 4-6 administrations of rhFVIII, and neutralizing antibodies reached levels similar to human patients (range 1-111 BU, median 6.0 BU) at the end of the study. There was no significant difference between the two studies or between genotypes in time to response or levels reached for binding and neutralizing antibodies. Inter...Continue Reading

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Citations

Apr 10, 2016·Journal of Thrombosis and Haemostasis : JTH·K R SørensenM Kjelgaard-Hansen
Jul 22, 2016·Haemophilia : the Official Journal of the World Federation of Hemophilia·K M LövgrenB Wiinberg
Sep 10, 2016·Haemophilia : the Official Journal of the World Federation of Hemophilia·K R ChristensenL N Nielsen
Jul 28, 2016·Haemophilia : the Official Journal of the World Federation of Hemophilia·L F D van VulpenR E G Schutgens
Apr 6, 2019·Expert Review of Hematology·Sarah J SchepLize F D van Vulpen
Mar 21, 2020·Journal of Thrombosis and Haemostasis : JTH·Karin M LövgrenParis Margaritis

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