{"title":"肥厚性滑膜血友病患者的强化 FVIII 替代治疗:随机研究。","authors":"Matteo Nicola Dario Di Minno, Ilenia Lorenza Calcaterra, Erminia Baldacci, Renato Marino, Federica Valeri, Rita Carlotta Santoro, Gianluigi Pasta, Carlo Martinoli","doi":"10.1016/j.jtha.2024.10.018","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>We explored the efficacy of intensive factor VIII (FVIII) replacement treatment in PwH with HS.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Intensive FVIII replacement in hemophilia patients with hypertrophic synovium: a randomized study.\",\"authors\":\"Matteo Nicola Dario Di Minno, Ilenia Lorenza Calcaterra, Erminia Baldacci, Renato Marino, Federica Valeri, Rita Carlotta Santoro, Gianluigi Pasta, Carlo Martinoli\",\"doi\":\"10.1016/j.jtha.2024.10.018\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>We explored the efficacy of intensive factor VIII (FVIII) replacement treatment in PwH with HS.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":17326,\"journal\":{\"name\":\"Journal of Thrombosis and Haemostasis\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.5000,\"publicationDate\":\"2024-10-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Thrombosis and Haemostasis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jtha.2024.10.018\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Thrombosis and Haemostasis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jtha.2024.10.018","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
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。
Intensive FVIII replacement in hemophilia patients with hypertrophic synovium: a randomized study.
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.
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.