Abstract
BackgroundFollowing 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. ObjectiveWe explored the use of N9‐GP prior to unilateral joint hemorrhage and compared to unmodified recombinant FIX (rFIX). MethodsPharmacodynamics, histology, and microcomputed tomography were used to assess the effects of prophylactic administration of glycoPEGylated FIX. ResultsIn 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. ConclusionsThese 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.
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