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Randomized Controlled Trial
. 2025 Feb;23(2):458-465.
doi: 10.1016/j.jtha.2024.10.018. Epub 2024 Oct 28.

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

Matteo Nicola Dario Di Minno  1 , Ilenia Lorenza Calcaterra  2 , Erminia Baldacci  3 , Renato Marino  4 , Federica Valeri  5 , Rita Carlotta Santoro  6 , Gianluigi Pasta  7 , Carlo Martinoli  8 ; Italian Association of Haemophilia Centers Musculoskeletal Working Group
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Free article
Randomized Controlled Trial

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

Matteo Nicola Dario Di Minno et al. J Thromb Haemost. 2025 Feb.
Free article

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Abstract

Background: 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.

Objectives: We explored the efficacy of intensive factor VIII (FVIII) replacement treatment in PwH with HS.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: hemophilia A; joint diseases; synovitis.

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Conflict of interest statement

Declaration of competing interests Matteo Nicola Dario Di Minno has acted as consultant/advisor and/or speaker for Bayer Healthcare, CSL Behring, Novo Nordisk, Pfizer, Roche, Sobi, Biomarin, and Takeda, outside the submitted work. Ilenia Calcaterra has acted as consultant/advisor and/or speaker for Bayer Healthcare, CSL Behring, Novo Nordisk, Pfizer, Roche, Sobi, Biomarin, and Takeda, outside the submitted work. Erminia Baldacci has acted as consultant/advisor and/or speaker for Bayer Healthcare, CSL Behring, Novo Nordisk, Pfizer, Roche, Sobi, and Takeda, outside the submitted work. Renato Marino has acted as consultant/advisor and/or speaker for Bayer Healthcare, CSL Behring, Novo Nordisk, Roche, Sobi, and Takeda, outside the submitted work. Federica Valeri has received honoraria for attending advisory boards and/or for speaking from Bayer Healthcare, Novo Nordisk, Pfizer, Sobi, and Takeda, outside the submitted work. Rita Carlotta Santoro has acted as consultant/advisor and/or speaker for Bayer Healthcare, CSL Behring, Novo Nordisk, Pfizer, Roche, Sobi, Biomarin, and Takeda, outside the submitted work. Gianluigi Pasta has received honoraria for attending symposia/congresses and/or for speaking and/or consulting, and/or has received research funding from Bayer, Novo Nordisk, Pfizer, Roche, Sobi, and Takeda. Carlo Martinoli has acted as paid consultant for Pfizer, and received speaker fees from Pfizer, Sobi, Takeda, Novartis, and Novo Nordisk, outside the submitted work.

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