Anti-Inhibitor Coagulant Complex Prophylaxis in Hemophilia with Inhibitors
Anti-Inhibitor Coagulant Complex Prophylaxis in Hemophilia with Inhibitors
复制标题
DOI：
10.1056/nejmoa1104435
复制
发表时间：
2011-11-03
影响因子：
158.5
通讯作者：
Mantovani, Lorenzo
中科院分区：
文献类型：
--
作者：
Leissinger, Cindy;Gringeri, Alessandro;Mantovani, Lorenzo
背景：患有严重血友病A和因子VIII抑制物的患者发生严重出血并发症和进展为终末期关节疾病的风险增加。有效的策略，以防止出血，在这样的patients尚未established.MethodsWe招募患者血友病A谁是年龄大于2岁，有高滴度抑制剂，并使用浓缩物称为旁路剂出血的前瞻性，随机，交叉研究比较6个月的抗抑制剂凝血复合物（AICC），每周非连续3天，以85 U/kg体重（+/- 15%）的目标剂量进行主动输注，并进行6个月的按需治疗（AICC，目标剂量为85 U/kg [+/- 15%]，用于出血发作）。两个治疗期之间间隔3个月的洗脱期，在此期间，患者接受按需治疗出血。主要结果是在每个6个月的治疗periods.ResultsThirty-four例患者进行随机化，26例患者完成了两个治疗期间，可以评价每协议的疗效分析出血事件的数量。与按需治疗相比，预防性治疗使所有出血事件减少62%（P < 0.001），关节积血减少61%（P < 0.001），靶关节出血减少72%（6个月治疗期间单个关节>= 3个关节积血）（P < 0.001）。33例随机分配的患者接受了至少一次研究药物输注，并进行了安全性评价。一名患者有过敏反应的studydrug.ConclusionsAICC预防剂量评估显着和安全地降低关节和其他出血事件的频率严重血友病A和因子VIII抑制剂的患者。（由巴克斯特生物科学公司资助; Pro-FEIBA ClinicalTrials.gov编号，NCT 00221195。）
BackgroundPatients with severe hemophilia A and factor VIII inhibitors are at increased risk for serious bleeding complications and progression to end-stage joint disease. Effective strategies to prevent bleeding in such patients have not yet been established.MethodsWe enrolled patients with hemophilia A who were older than 2 years of age, had high-titer inhibitors, and used concentrates known as bypassing agents for bleeding in a prospective, randomized, crossover study comparing 6 months of anti-inhibitor coagulant complex (AICC), infused prophylactically at a target dose of 85 U per kilogram of body weight (+/- 15%) on 3 nonconsecutive days per week, with 6 months of on-demand therapy (AICC at a target dose of 85 U per kilogram [+/- 15%] used for bleeding episodes). The two treatment periods were separated by a 3-month washout period, during which patients received on-demand therapy for bleeding. The primary outcome was the number of bleeding episodes during each 6-month treatment period.ResultsThirty-four patients underwent randomization; 26 patients completed both treatment periods and could be evaluated per protocol for the efficacy analysis. As compared with on-demand therapy, prophylaxis was associated with a 62% reduction in all bleeding episodes (P < 0.001), a 61% reduction in hemarthroses (P < 0.001), and a 72% reduction in target-joint bleeding (>= 3 hemarthroses in a single joint during a 6-month treatment period) (P < 0.001). Thirty-three randomly assigned patients received at least one infusion of the study drug and were evaluated for safety. One patient had an allergic reaction to the study drug.ConclusionsAICC prophylaxis at the dosage evaluated significantly and safely decreased the frequency of joint and other bleeding events in patients with severe hemophilia A and factor VIII inhibitors. (Funded by Baxter BioScience; Pro-FEIBA ClinicalTrials.gov number, NCT00221195.)