F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Hemophilia of Georgia Center for Bleeding & Clotting Disorders of Emory, Emory University School of Medicine, Atlanta, Georgia, USA.
Haemophilia. 2022 Nov;28(6):1033-1043. doi: 10.1111/hae.14642. Epub 2022 Jul 29.
Emicizumab prophylaxis significantly reduces bleeding events; however, the associated impact on bone/joint health is unknown.
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).
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.
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.
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.
依库珠单抗预防治疗显著减少出血事件；然而，其对骨骼/关节健康的影响尚不清楚。
探讨在 HAVEN 3 研究（NCT02847637）中，未接受凝血因子 VIII 抑制剂治疗的血友病 A 患者（PwHA）中，依库珠单抗预防治疗对骨骼/关节健康的影响。
在接受依库珠单抗治疗的 PwHA（n=134）中，于基线和第 49 周、97 周时评估血友病关节健康评分（HJHS；v2.1），在接受依库珠单抗治疗 24 周后转为依库珠单抗治疗的 PwHA（n=17）中，于基线和第 49 周、73 周和 97 周时评估 HJHS。在 117 名 PwHA 中，在基线时以及第 13 周、25 周、49 周和 73 周时测量骨骼和关节生物标志物。
与未接受预防治疗、年龄≥40 岁或基线时无目标关节的 PwHA 相比，之前接受过凝血因子 VIII 预防治疗、年龄＜40 岁或基线时无目标关节的 PwHA 的 HJHS 更低。在研究入组时至少有一个目标关节的 PwHA（n=71）中，第 49 周时观察到 HJHS 关节特异性域的临床显著平均（95%置信区间）改善值为-2.13（-3.96，-.29）；这些改善在第 97 周时仍保持。年龄在 12-39 岁的 PwHA 的 HJHS 也观察到改善。在依库珠单抗预防治疗期间，骨吸收/形成、软骨降解/合成和炎症的生物标志物均无显著变化。
在 HAVEN 3 研究中，接受依库珠单抗治疗 48 周后，年轻的 PwHA 和有目标关节的 PwHA 的 HJHS 观察到有临床意义的改善。在依库珠单抗预防治疗 72 周期间，骨骼/关节健康的生物标志物没有显示出显著变化。
