Klamroth Robert, Kragh Nana, Arnaud Alix, Guyot Patricia, Wilson Amanda, Wojciechowski Piotr, Wdowiak Marlena, Margas Wojciech, Bystrická Linda, Tosetto Alberto
Vivantes Klinikum im Friedrichshain, Berlin, Germany.
Medical Faculty, Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, University of Bonn, Bonn, Germany.
Adv Ther. 2025 Jan;42(1):427-441. doi: 10.1007/s12325-024-03032-3. Epub 2024 Nov 22.
In the Phase 3 XTEND-1 trial, (NCT04161495) efanesoctocog alfa prophylaxis provided superior bleed protection versus pre-study factor VIII (FVIII) replacement therapy in patients with severe haemophilia A. The aim of this study was to indirectly compare bleed outcomes between efanesoctocog alfa and standard/extended half-life (SHL and EHL) FVIII replacement therapies in adolescent and adult patients with severe haemophilia A without inhibitors.
A systematic literature review was conducted to identify Phase 3 trials of EHL and SHL FVIII replacement therapies for comparison with efanesoctocog alfa data from XTEND-1. Matching-adjusted indirect comparisons were used to compare annualised bleeding rates (ABRs) for any, treated, joint, and spontaneous bleeds between efanesoctocog alfa and comparators. The estimates from respective comparisons were pooled using random-effect meta-analyses to evaluate the overall difference between efanesoctocog alfa and comparator therapies.
Four EHL therapies (rurioctocog alfa pegol, efmoroctocog alfa, turoctocog alfa pegol, damoctocog alfa pegol) and two octocog alfa SHL therapies were included. In meta-analyses, efanesoctocog alfa was associated with significantly lower ABRs for any [mean difference (95% CI) - 2.24 ( - 3.24; - 1.25)], spontaneous [ - 1.52 ( - 2.33; - 0.72)], and joint bleeds [ - 1.60 ( - 2.32; - 0.88)] versus EHL therapies, and with significantly lower ABRs for any [ - 3.61 ( - 4.43; - 2.79)], treated [ - 1.55 ( - 1.89; - 1.20)], spontaneous [ - 2.52 ( - 3.31; - 1.72)], and joint bleeds [ - 3.42 ( - 4.77; - 2.08)] versus SHL therapies.
Efanesoctocog alfa was associated with significantly lower ABRs (any, spontaneous and joint) compared with EHL or SHL prophylaxis therapies. Patients had, on average, 2.2 and 3.6 fewer bleeds per year versus EHL and SHL therapies, respectively.
在3期XTEND - 1试验（NCT04161495）中，对于重度甲型血友病患者，艾美赛珠单抗预防治疗在出血保护方面优于研究前的凝血因子VIII（FVIII）替代疗法。本研究的目的是间接比较艾美赛珠单抗与标准/延长半衰期（SHL和EHL）FVIII替代疗法在无抑制剂的重度甲型血友病青少年和成年患者中的出血结局。
进行了一项系统的文献综述，以确定EHL和SHL FVIII替代疗法的3期试验，以便与XTEND - 1中的艾美赛珠单抗数据进行比较。使用匹配调整间接比较来比较艾美赛珠单抗与对照药物之间任何、治疗、关节和自发性出血的年化出血率（ABR）。使用随机效应荟萃分析汇总各自比较的估计值，以评估艾美赛珠单抗与对照疗法之间的总体差异。
纳入了四种EHL疗法（聚乙二醇重组人凝血因子VIII、重组人凝血因子VIII、聚乙二醇化重组人凝血因子VIII、重组人凝血因子VIII聚乙二醇化）和两种SHL凝血因子VIII疗法。在荟萃分析中，与EHL疗法相比，艾美赛珠单抗在任何[平均差异（95%CI）-2.24（-3.24；-1.25）]、自发性[-1.52（-2.33；-0.72）]和关节出血[-1.60（-2.32；-0.88）]方面的ABR显著更低；与SHL疗法相比，在任何[-3.61（-4.43；-2.79）]、治疗性[-1.55（-1.89；-1.20）]、自发性[-2.52（-3.31；-1.72）]和关节出血[-3.42（-4.77；-2.08）]方面的ABR显著更低。
与EHL或SHL预防疗法相比，艾美赛珠单抗的ABR（任何、自发性和关节）显著更低。与EHL和SHL疗法相比，患者平均每年的出血次数分别减少2.2次和3.6次。
