Efanesoctocog Alfa Prophylaxis for Patients with Severe Hemophilia A
Efanesoctocog Alfa Prophylaxis for Patients with Severe Hemophilia A
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DOI：
10.1056/nejmoa2209226
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发表时间：
2023-01-26
影响因子：
158.5
通讯作者：
Knobe, Karin
中科院分区：
文献类型：
--
作者：
von Drygalski, Annette;Chowdary, Pratima;Knobe, Karin
defanesoctocog alfa通过克服血管性血友病因子施加的半衰期上限提供高持续的因子VIII活性。efanesoccog alfa预防和治疗既往治疗过的严重血友病A患者出血发作的有效性、安全性和药代动力学尚不清楚。方法：我们进行了一项3期研究，涉及12岁或以上的严重血友病a患者。在a组中，患者接受每周一次的efanesoctocog alfa预防治疗（每公斤体重50 IU），持续52周。在B组，患者接受依需efanesoctocog alfa治疗26周，随后每周一次efanesoctocog alfa预防26周。主要终点为A组的年平均出血率；关键的次要终点是A组预防期间的年化出血率与研究前因子VIII预防期间的出血率的患者内比较。其他终点包括出血发作的治疗、安全性、药代动力学、身体健康、疼痛和关节健康的变化。结果A组133例患者，年化出血率中位数为0（四分位数范围0 ~ 1.04），估计年化出血率中位数为0.71（95%可信区间[CI] 0.52 ~ 0.97）。平均年化出血率从2.96 （95% CI, 2.00 - 4.37）下降到0.69 (95% CI, 0.43 - 1.11)，这一发现显示了研究前因子VIII预防的优势(P
BACKGROUNDEfanesoctocog alfa provides high sustained factor VIII activity by overcoming the von Willebrand factor-imposed half-life ceiling. The efficacy, safety, and pharmacokinetics of efanesoctocog alfa for prophylaxis and treatment of bleeding episodes in previously treated patients with severe hemophilia A are unclear.METHODSWe conducted a phase 3 study involving patients 12 years of age or older with severe hemophilia A. In group A, patients received once-weekly prophylaxis with efanesoctocog alfa (50 IU per kilogram of body weight) for 52 weeks. In group B, patients received on-demand treatment with efanesoctocog alfa for 26 weeks, followed by once-weekly prophylaxis with efanesoctocog alfa for 26 weeks. The primary end point was the mean annualized bleeding rate in group A; the key secondary end point was an intrapatient comparison of the annualized bleeding rate during prophylaxis in group A with the rate during prestudy factor VIII prophylaxis. Additional end points included treatment of bleeding episodes, safety, pharmacokinetics, and changes in physical health, pain, and joint health.RESULTSIn group A (133 patients), the median annualized bleeding rate was 0 (interquartile range, 0 to 1.04), and the estimated mean annualized bleeding rate was 0.71 (95% confidence interval [CI], 0.52 to 0.97). The mean annualized bleeding rate decreased from 2.96 (95% CI, 2.00 to 4.37) to 0.69 (95% CI, 0.43 to 1.11), a finding that showed superiority over prestudy factor VIII prophylaxis (P