Changes in Hypertrophic Synovium Status in Adult Patients With Severe Hemophilia A Receiving Emicizumab Prophylaxis: The RESOLVE Study.

BACKGROUND: Evidence on the impact of emicizumab on joint health, particularly hypertrophic synovium (HS), remains limited. OBJECTIVES: To evaluate changes in HS, using point-of-care ultrasound and clinical examination in People with Haemophilia (PwH) switching from replacement therapy to emicizumab. METHODS: The RESOLVE study is a retrospective observational, multicenter cohort study including adults with severe hemophilia A (FVIII<1%), with and without anti-FVIII inhibitors, who started a treatment with emicizumab and were followed for at least 2 years. Clinical data, annualized bleeding rates (ABR,AjBR), HJHS, and HEAD-US assessments were collected during replacement therapy and after ≥2-year emicizumab. HS was graded according to the HEAD-US protocol. Changes in HS represented the primary outcome. RESULTS: Fifty-two PwH (mean±SDage: 37.9±12.1years) were enrolled, with data on 298 joints. Emicizumab prophylaxis resulted in a significant reduction in ABR and AjBR compared with replacement therapy, with an increase in participants achieving ABR zero and AjBRzero. At baseline, HS was present in 22.5% of joints. After ≥2-year-emicizumab, HS was improved/resolved in 53.7% of affected joints, while it persisted in 38.8% and worsened in 7.5% of joints. New-onset HS was developed in 6.1% of previously unaffected joints. Baseline structural joint damage was strongly associated with the presence and persistence of HS. CONCLUSIONS: In this real-world setting, emicizumab provides bleeding protection and is associated with reduction/resolution of HS in more than 50% of affected joints. In case of persistent HS, a tailored approach to joint health management may be needed to fully prevent or reverse HS.