Indiana Hemophilia and Thrombosis Center, Indianapolis, IN, USA.
Haemophilia. 2014 Jan;20(1):e23-31. doi: 10.1111/hae.12329.
Recombinant activated factor VII (rFVIIa) is indicated for treatment of bleeding in congenital haemophilia with inhibitors (CHwI) using 90 μg kg(-1) every 2-3 h (EU and US) or a single 270 μg kg(-1) dose (EU only) with ~90% efficacy reported for both regimens. Dosing of rFVIIa varies, and home treatment makes assessment of frequency of doses >90 μg kg(-1), the intervals before additional treatment, and the risk for thromboembolic events (TEs) more difficult. This post hoc analysis assessed the safety and distribution of rFVIIa dosing in CHwI and the impact of >240 μg kg(-1) dosing on subsequent bypassing agent (BPA) dosing interval and frequency. Data regarding on-demand or prophylactic rFVIIa dosing, TE incidence and subsequent BPA dosing after high rFVIIa doses were compiled from multiple sources incorporating safety surveillance. A total of 61 734 rFVIIa doses were reported in 481 patients treated for 3947 bleeds and for 43 135 prophylaxis days. Over half (52%) exceeded 120 μg kg(-1), 37% exceeded 160 μg kg(-1) and 15% exceeded 240 μg kg(-1). Subsequent doses of BPA(s) were administered after 38% of initial and 49% of any rFVIIa dose >240 μg kg(-1), and were most frequently administered ≥24 h after initial (40%) or any (53%) doses >240 μg kg(-1). No TEs were reported. The findings of this analysis show that rFVIIa doses >90 μg kg(-1) are utilized for 'real-world' treatment of children and adults. When additional BPA was administered following an rFVIIa dose >240 μg kg(-1), reported intervals were prolonged, often ≥24 h. No safety issues were identified in the 61,734 doses analysed.
重组活化因子 VII（rFVIIa）被批准用于治疗伴有抑制剂的先天性血友病（CHwI）出血，剂量为每 2-3 小时 90μg/kg（欧盟和美国）或单次 270μg/kg（仅欧盟），两种方案的有效率约为 90%。rFVIIa 的剂量不同，家庭治疗使得评估 >90μg/kg 的剂量频率、追加治疗前的间隔时间以及血栓栓塞事件（TE）的风险更加困难。本事后分析评估了 CHwI 中 rFVIIa 给药的安全性和分布情况，以及 >240μg/kg 剂量对随后旁路剂（BPA）给药间隔和频率的影响。从多个来源整合安全性监测数据，收集了关于按需或预防性 rFVIIa 给药、TE 发生率以及高 rFVIIa 剂量后随后 BPA 给药的资料。共报告了 481 例患者接受 61734 次 rFVIIa 治疗 3947 次出血和 43135 次预防治疗的剂量。超过一半（52%）超过 120μg/kg，37%超过 160μg/kg，15%超过 240μg/kg。初始剂量 >240μg/kg 后有 38%和任何 rFVIIa 剂量 >240μg/kg 后有 49%的患者随后给予 BPA(s)，初始剂量 >240μg/kg 后最常于 40%和任何剂量 >240μg/kg 后 53%时给予。未报告 TEs。本分析结果表明，rFVIIa 剂量 >90μg/kg 用于儿童和成人的“真实世界”治疗。当给予 rFVIIa 剂量 >240μg/kg 后再给予 BPA 时，报告的间隔时间延长，通常 >24 小时。在分析的 61734 个剂量中未发现安全性问题。
