Joint health

Joint damage has a major impact throughout the life of a patient with haemophilia A

Joint damage in haemophilia A is a result of repeated bleeding within joints and leads to pain, deformity and disability1. In a long-term joint outcomes study, over 85% of people with haemophilia A had joint damage by age 182.

The extent of joint damage does not correlate with the number of clinical bleeds, suggesting that subclinical bleeds contribute to the development of arthropathy1,3.

Joint damage in young boys with severe haemophilia A does not correlate with the number of clinical joint bleeds

jointdamage substudy

FVIII prophylaxis has been shown to preserve joint health3,4. FVIII may also play a direct role in controlling inflammation5 and preserving bone mineral density6.

Data on the effects of emicizumab on joint health are limited7.

To prevent joint and bone damage we need to be able to identify damage at an early stage. Although a number of biomarkers of collagen (a major component of bone and cartilage) have been described, few have an established association with clinical outcomes.

To understand how we can help to preserve joint health in people with inhibitors we need to increase our understanding of how treatment decisions impact joint and bone health, and to find ways to detect early signs of joint and bone damage.

Joint health biomarkers sub-study

Sub-study lead investigators

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Jess Snedeker

Head of the Institute for Biomechanics, ETH, Zürich, and Head of Biomechanics, University Clinic Balgrist, Zürich, Switzerland

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Sander Botter

Head of the Swiss Center for Musculoskeletal Biobanking, Balgrist Campus AG, Zürich, Switzerland

MOTIVATE will evaluate the impact of different treatment approaches on levels of established bone and joint health biomarkers. The sub-study also aims to identify and validate new markers of early-onset joint degeneration.

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What is needed for this analysis?

A blood sample of 6–10 mL collected before the start of the study (or within the first month of treatment) and once per year


  1. Valentino LA. <i>J Thromb Haemost</i> 2010; 8:1895-902
  2. Warren BB et al. <i>Blood Adv</i> 2020; 4:2451-9
  3. Manco-Johnson MJ et al. <i>N Engl J Med</i> 2007; 357:535-44
  4. Fischer K et al. <i>Blood</i> 2002; 99:2337-41
  5. Hua B et al. <i>Haemophilia</i> 2017; 23:e294-300
  6. Liel MS et al. <i>Br J Haematol</i> 2012; 158:140-3
  7. Knight T and Callaghan MU. <i>Ther Adv Hematol</i> 2018; 9:319-34