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

IF 5.5 2区医学 Q1 HEMATOLOGY Journal of Thrombosis and Haemostasis Pub Date : 2024-10-28 DOI:10.1016/j.jtha.2024.10.018

Matteo Nicola Dario Di Minno, Ilenia Lorenza Calcaterra, Erminia Baldacci, Renato Marino, Federica Valeri, Rita Carlotta Santoro, Gianluigi Pasta, Carlo Martinoli

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Abstract

Background and aims: Hypertrophic synovium (HS) is a marker of disease activity in patients with haemophilia (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.

Methods: In a randomized, open-label study, PwH with HS were randomized to receive pharmacokinetics-driven prophylaxis targeting a FVIII through level of 8%-12% (intensive treatment arm [ITA]) or 3-5% (standard treatment arm [STA]). The primary outcome was HS reduction/resolution in the two 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 (ABR) and a higher rate of ABR zero in the ITA than in the STA. HS reduction/resolution was reported by 35.9% of cases in the ITA and by 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. A COX regression showed that ITA was associated to HS reduction/resolution (Hazard ratio [HR]: 4.75, 95% confidence interval [CI]: 1.36-16.57, p=0.014) and to HS complete resolution (HR: 10.79, 95%CI: 1.38-84.45, p=0.023). The analysis on the 127 joints with HS (54 elbows, 41 knees and 32 ankles) consistently confirmed similar results.

Conclusions: 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 as compared to the STA.

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肥厚性滑膜血友病患者的强化 FVIII 替代治疗：随机研究。

背景和目的：肥厚性滑膜（HS）是血友病患者（PwH）疾病活动的标志。尽管一些建议提出要加强对血友病患者的预防，但目前尚无有效的时间表。我们探讨了强化因子 VIII（FVIII）替代治疗对血友病患者的疗效：在一项随机、开放标签研究中，患有 HS 的 PwH 被随机分配接受药代动力学驱动的预防治疗，目标是 FVIII 通过水平达到 8%-12%（强化治疗组 [ITA]）或 3%-5%（标准治疗组 [STA]）。两个治疗组的主要结果是HS减少/缓解：共有 39 名患者被随机分配到 ITA 治疗组，36 名患者被随机分配到 STA 治疗组。在研究过程中，我们发现与 STA 相比，ITA 的年出血率（ABR）更低，且 ABR 零发生率更高。据报告，35.9%的病例（ITA）和 8.4% 的病例（STA）HS 减少/消退。具体而言，在 ITA 中，10.3% 的病例实现了 HS 减少，25.6% 的病例完全消除了 HS，而在 STA 中，这一比例分别为 5.6% 和 2.8%。COX回归显示，ITA与HS缩小/消退（危险比[HR]：4.75，95%置信区间[CI]：1.36-16.57，P=0.014）和HS完全消退（HR：10.79，95%置信区间[CI]：1.38-84.45，P=0.023）相关。对127个患有HS的关节（54个肘关节、41个膝关节和32个踝关节）的分析也证实了类似的结果：在这项随机研究中，我们发现与STA相比，ITA的HS减少/缓解率高5倍，HS缓解率高10倍。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Thrombosis and Haemostasis 医学-外周血管病

CiteScore

24.30

自引率

3.80%

发文量

321

审稿时长

1 months

期刊介绍： The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.