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

J Thromb Haemost. 2019 Aug;17(8):1240-1246. doi: 10.1111/jth.14527. Epub 2019 Jun 28.

Abstract

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.

Keywords: bone; factor IX; hemarthrosis; hemophilia; joint.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Drug Administration Schedule
  • Factor IX / administration & dosage
  • Factor IX / genetics
  • Factor IX / metabolism*
  • Factor IX / pharmacokinetics
  • Half-Life
  • Hemarthrosis / diagnostic imaging
  • Hemarthrosis / drug therapy*
  • Hemarthrosis / genetics
  • Hemarthrosis / metabolism
  • Hemophilia B / drug therapy*
  • Hemophilia B / genetics
  • Hemophilia B / metabolism
  • Hemostatics / administration & dosage*
  • Hemostatics / pharmacokinetics
  • Joints / diagnostic imaging
  • Joints / drug effects*
  • Joints / pathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / pharmacokinetics
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacokinetics

Substances

  • Hemostatics
  • Recombinant Proteins
  • nonacog beta pegol
  • Polyethylene Glycols
  • Factor IX