Improved joint health in subjects with severe haemophilia A treated prophylactically with recombinant factor VIII Fc fusion protein

Haemophilia. 2018 Jan;24(1):77-84. doi: 10.1111/hae.13353. Epub 2017 Oct 30.

Abstract

Introduction: Joint arthropathy is the long-term consequence of joint bleeding in people with severe haemophilia.

Aim: This study assessed change in joint health over time in subjects receiving recombinant factor VIII Fc fusion protein (rFVIIIFc) prophylaxis.

Methods: ALONG is the phase 3 pivotal study in which the benefit of rFVIIIFc as a prophylactic treatment for bleeding control was shown in previously treated severe haemophilia patients ≥12 years of age (arm 1: 25-65 IU/kg every 3-5 days, arm 2: 65 IU/kg weekly and arm 3: episodic). After completing ALONG, subjects had the option to enrol into the extension study (ASPIRE). This interim, post hoc analysis assessed changes in joint health over ~2.8 years in these patients.

Results: Forty-seven subjects had modified Haemophilia Joint Health Score (mHJHS) data at A-LONG baseline, ASPIRE baseline and ASPIRE Year 1 and Year 2. Compared with A-LONG baseline (23.4), mean improvement at ASPIRE Year 2 was -4.1 (95% confidence interval [CI], -6.5, -1.8; P = .001). Regardless of prestudy treatment regimen, subjects showed continuous improvement in mHJHS from A-LONG baseline through ASPIRE Year 2 (prestudy prophylaxis: -2.4, P = .09; prestudy episodic treatment: -7.2, P = .003). Benefits were seen in subjects with target joints (-5.6, P = .005) as well as those with severe arthropathy (-8.8, P = .02). The mHJHS components with the greatest improvement at ASPIRE Year 2 were swelling (-1.4, P = .008), range of motion (-1.1, P = .03) and strength (-0.8, P = .04).

Conclusions: Prophylaxis with rFVIIIFc may improve joint health over time regardless of prestudy prophylaxis or episodic treatment regimens.

Keywords: arthropathy; factor VIII; haemarthrosis; haemophilia; joint health; prophylaxis.

MeSH terms

  • Adolescent
  • Adult
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Factor VIII / therapeutic use*
  • Hemophilia A / complications
  • Hemophilia A / drug therapy*
  • Hemophilia A / pathology
  • Humans
  • Immunoglobulin Fc Fragments / therapeutic use*
  • Joint Diseases / complications
  • Joint Diseases / diagnosis
  • Joints / physiopathology*
  • Male
  • Middle Aged
  • Range of Motion, Articular
  • Recombinant Fusion Proteins / therapeutic use*
  • Severity of Illness Index
  • Young Adult

Substances

  • Immunoglobulin Fc Fragments
  • Recombinant Fusion Proteins
  • factor VIII-Fc fusion protein
  • Factor VIII