Effect of emicizumab prophylaxis on bone and joint health markers in people with haemophilia A without factor VIII inhibitors in the HAVEN 3 study

Abstract

Introduction Emicizumab prophylaxis significantly reduces bleeding events; however, the associated impact on bone/joint health is unknown. Aim To explore the effect of emicizumab prophylaxis on bone/joint health in people with haemophilia A (PwHA) without FVIII inhibitors enrolled in HAVEN 3 (NCT02847637). Methods Haemophilia joint health scores (HJHS; v2.1) were evaluated at baseline and Weeks 49 and 97 in PwHA receiving emicizumab (n = 134), and at baseline and Weeks 49, 73 and 97 in PwHA who switched to emicizumab after 24 weeks of no prophylaxis (n = 17). Bone and joint biomarkers were measured in 117 PwHA at baseline and at Weeks 13, 25, 49 and 73. Results HJHS was lower for PwHA who were previously on FVIII prophylaxis, aged <40 years or had no target joints at baseline compared with PwHA who were receiving no prophylaxis, aged ≥40 years or with target joints. Clinically significant mean (95% confidence interval) improvements from baseline of −2.13 (−3.96, −.29) in HJHS joint‐specific domains were observed at Week 49 in PwHA with at least one target joint at study entry (n = 71); these changes were maintained through Week 97. Improvements in HJHS from baseline were also observed for PwHA aged 12–39 years. Biomarkers of bone resorption/formation, cartilage degradation/synthesis, and inflammation did not change significantly during emicizumab prophylaxis. Conclusions Clinically relevant improvements in HJHS were observed in younger PwHA and those with target joints after 48 weeks of emicizumab in HAVEN 3. Biomarkers of bone/joint health did not show significant changes during 72 weeks of emicizumab prophylaxis.

Gene therapy for hemophilia: looking beyond factor expression

“…33 Recently, Kiialainen et al . 34 reported a clinically relevant improvement in Hemophilia Joint Health Score (HJHS) in hemophilia A patients without inhibitors under emicizumab prophylaxis. This is the first evaluation of the impact of a “stable hemostasis” on joint health, without peak and trough levels of regular factor replacement and it opens the debate as to whether patients reaching stable factor levels after gene therapy will have similar improvement.…”

“…It is already known that tertiary prophylaxis with factor replacement improves function, quality of life, activity, and pain, although it did not impact joint structure assessment by magnetic resonance imaging (MRI). 33 Recently, Kiialainen et al 34 reported a clinically relevant improvement in Hemophilia Joint Health Score (HJHS) in hemophilia A patients without inhibitors under emicizumab prophylaxis. This is the first evaluation of the impact of a "stable hemostasis" on joint health, without peak and trough levels of regular factor replacement and it opens the debate as to whether patients reaching stable factor levels after gene therapy will have similar improvement.…”

Sports participation, Injuries and Bleeds in People with Haemophilia

“…This study showed high sports participation by young Dutch PWH, similar to the general Dutch general population 127 . Previous studies in Dutch 24,26 , British 92 , Australian 71 , Irish 90 and Israeli 132 PWH already reported high participation in PWH. These were cross-sectional studies, most of them 24,26,71,90,132 only reporting being active in sports or not.…”

“…Previous studies in Dutch 24,26 , British 92 , Australian 71 , Irish 90 and Israeli 132 PWH already reported high participation in PWH. These were cross-sectional studies, most of them 24,26,71,90,132 only reporting being active in sports or not. Maximal follow-up was three months 132 .…”

“…Although emicizumab is claimed to have activity levels similar to 10 IU/dl FVIII, the effects of this on prevalence and prevention on sports injuries and sports-induced bleeds need to be studied. With the increase in sports participation, sports and physical activity seem to become more important outcome measures in haemophilia research, including in studies on the clinical application and efficacy of emicizumab [85][86][87][88][89][90] .…”