Intensive FVIII replacement in hemophilia patients with hypertrophic synovium: a randomized study.

Hypertrophic synovium (HS) is a marker of disease activity in persons with hemophilia (PwH). Although some recommendations suggest intensifying prophylaxis in PwH with HS, no validated schedules are available. We explored the efficacy of intensive factor VIII (FVIII) replacement treatment in PwH with HS. In a randomized, open-label study, PwH with HS were randomized to receive pharmacokinetics-driven prophylaxis targeting a FVIII trough level of 8% to 12% (intensive treatment arm [ITA]) or 3% to 5% (standard treatment arm [STA]). The primary outcome was HS reduction/resolution in the 2 treatment arms. A total of 39 PwH were randomized to ITA and 36 to STA. During the study, we found a lower annual bleeding rate and a higher rate of annual bleeding rate zero in the ITA than in the STA. HS reduction/resolution was reported in 35.9% of cases in the ITA and 8.4% in the STA. In detail, in the ITA ,10.3% achieved HS reduction and 25.6% complete HS resolution, as compared to 5.6% and 2.8% in the STA. Cox regression showed that ITA was associated with HS reduction/resolution (hazard ratio: 4.75; 95% CI: 1.36-16.57; P = .014) and HS complete resolution (hazard ratio: 10.79; 95% CI: 1.38-84.45; P = .023). The analysis of the 127 joints with HS (54 elbows, 41 knees, and 32 ankles) consistently confirmed similar results. In this randomized study, we found a ∼5-fold higher rate of HS reduction/resolution and a ∼10-fold higher rate of HS resolution in the ITA than in the STA. Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Matteo Nicola Dario Di Minno, Ilenia Lorenza Calcaterra, Erminia Baldacci, Renato Marino, Federica Valeri, Rita Carlotta Santoro, Gianluigi Pasta, Carlo Martinoli, Italian Association of Haemophilia Centers Musculoskeletal Working Group. Intensive FVIII replacement in hemophilia patients with hypertrophic synovium: a randomized study. Journal of thrombosis and haemostasis : JTH. 2025 Feb;23(2):458-465

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PMID: 39476971

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