Prophylactic administration of glycoPEGylated factor IX provides protection and joint outcome superior to recombinant factor IX after induced joint bleeding

Background Following induced joint hemorrhage, hemophilia B results in the abnormal persistence of iron deposition, inflammation, and neovascularity of the synovial tissue, as well as deterioration of the bone articular surface and strength. Previously, we demonstrated that a factor IX (FIX) replace...

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Published inJournal of thrombosis and haemostasis Vol. 17; no. 8; pp. 1240 - 1246
Main Authors Sun, Junjiang, Livingston, Eric W., Broberg, Mie L., Johansen, Peter B., Ley, Carsten D., Knudsen, Tom, Ezban, Mirella, Bateman, Ted, Monahan, Paul E., Taves, Sarah
Format Journal Article
LanguageEnglish
Published England Wiley Subscription Services, Inc 01.08.2019
Subjects
Bleeding
bone
Coagulation factors
Computed tomography
factor IX
Factor IX deficiency
hemarthrosis
Hemophilia
Hemorrhage
joint
Pharmacodynamics
Rodents
factor IX
hemophilia
bone
joint
hemarthrosis
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Summary:Background Following induced joint hemorrhage, hemophilia B results in the abnormal persistence of iron deposition, inflammation, and neovascularity of the synovial tissue, as well as deterioration of the bone articular surface and strength. Previously, we demonstrated that a factor IX (FIX) replacement protein with extended circulating FIX activity, glycoPEGylated FIX nonacog beta pegol (N9‐GP), could improve synovial and osteochondral parameters in F9 knockout mice when administered after joint injury. Objective We explored the use of N9‐GP prior to unilateral joint hemorrhage and compared to unmodified recombinant FIX (rFIX). Methods Pharmacodynamics, histology, and microcomputed tomography were used to assess the effects of prophylactic administration of glycoPEGylated FIX. Results In comparison to rFIX, N9‐GP significantly improved soft tissue histological parameters, as well as bone outcome at 2 weeks post injury, while performing equally in reduction of blood present in the joint space assessed 1 day after injury. Conclusions These results indicate that, in comparison to rFIX, the prophylactic use of extended half‐life FIX provides superior protection from bleeding‐induced joint damage, manifested by improved correction of histologic parameters.
ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/jth.14527