Objective:
Multiple factors contribute to bone health, including physical activity, lifestyle, diet, and certain medical conditions. Emicizumab prophylaxis has been shown to reduce the frequency of bleeding episodes in persons with hemophilia A (PwHA). In this study, we explored the potential effect of emicizumab prophylaxis on joint health scores and biomarkers of bone health in PwHA without factor VIII (FVIII) inhibitors who participated in the HAVEN 3 clinical trial.
Methods:
The Hemophilia Joint Health Score (HJHS) is a tool used to assess joint function and gait, with a lower score indicating better joint health. We obtained HJHS scores from 107 PwHA before starting emicizumab and 48 weeks after starting emicizumab. We also measured biomarkers for bone and joint health in blood samples from 117 PwHA; blood samples were taken before starting emicizumab, and periodically after starting emicizumab (3, 6, 12, and 18 months). In total, 78 people received both the HJHS evaluations and biomarker testing.
Summary:
PwHA who were previously on FVIII prophylaxis and those with no target joints had lower HJHS (indicating better joint health) before starting emicizumab. Average HJHS values decreased 48 weeks after starting emicizumab, indicating improvement in joint function and health. There were 71 people with at least one target joint; among those we saw improvements from baseline in the average total HJHS (-2.25 [95% confidence interval: -4.12, -0.39]) and significant improvements in the joint-specific part of the HJHS, which excluded gait (-2.23 [95% confidence interval:-4.07, -0.38]). Improvement was consistent across HJHS for different joints. Before starting emicizumab, there were no significant differences in biomarkers for bone health between PwHA previously on FVIII prophylaxis or on on-demand treatment, or those with or without target joints. The average values measured for most of the markers were within normal ranges, or were similar to values for healthy individuals documented in the scientific literature; although there was a large variation among individuals tested. None of the measured biomarkers changed significantly during emicizumab prophylaxis. Among the adolescents in this study, levels for three of the biomarkers known to increase during periods of growth were higher than in the adults at each time point.
Conclusions:
This analysis showed clinically relevant improvements in HJHS (defined as a ≥2-point decrease in the joint-specific part of the HJHS) 48 weeks after starting emicizumab prophylaxis in PwHA without FVIII inhibitors. Average values for most of the biomarkers for bone and joint health were similar to values reported in healthy people without hemophilia A, and did not show significant changes during emicizumab prophylaxis. We saw no indication of worsening of the markers for bone and joint health. Additional data are needed to better understand the long-term effect of prophylaxis on bone and joint health.