Álvarez Román María Teresa, Kragh Nana, Guyot Patricia, Wilson Amanda, Wojciechowski Piotr, Margas Wojciech, Wdowiak Marlena, Santagostino Elena, Arnaud Alix
Thrombosis and Haemostasis Unit, University Hospital La Paz, Madrid, Spain.
Sobi, Swedish Orphan Biovitrum AB, 112 76, Stockholm, Sweden.
Adv Ther. 2025 Jan;42(1):442-455. doi: 10.1007/s12325-024-03031-4. Epub 2024 Nov 22.
The phase 3 XTEND-1 trial (NCT04161495) demonstrated that efanesoctocog alfa prophylaxis provided superior bleed protection compared with pre-trial factor VIII (FVIII) prophylaxis in patients with severe haemophilia A. The aim of this study was to indirectly compare the efficacy of efanesoctocog alfa with non-factor replacement therapy emicizumab in adolescent and adult patients with severe haemophilia A without inhibitors.
A systematic literature review was conducted to identify phase 3 trials of emicizumab. Matching-adjusted indirect comparisons were used to compare annualised bleeding rates (ABRs) for any, treated, joint, and spontaneous bleeds, and joint health (measured using Hemophilia Joint Health Score [HJHS]), between efanesoctocog alfa and emicizumab. Estimated effects for different emicizumab regimens were pooled using random-effect meta-analysis to evaluate the overall difference in bleed outcomes between efanesoctocog alfa and emicizumab.
One emicizumab trial was included (HAVEN 3), which investigated three dosing regimens. In meta-analyses, efanesoctocog alfa once-weekly (Q1W) was associated with significantly lower ABRs for any (incidence rate ratio [95% CI] 0.33 [0.20; 0.53]), any treated (0.49 [0.30; 0.80]) and treated joint (0.51 [0.28; 0.91]) bleeds compared with emicizumab Q1W in non-inhibitor patients with prior prophylaxis or on-demand treatment. Efanesoctocog alfa Q1W was also associated with a significantly better improvement from baseline in HJHS Joint Score (mean difference [95% CI] -2.06 [-3.97; -0.14]) and Total Score (-2.37 [-4.36; -0.39]) versus emicizumab Q1W or every 2 weeks.
Efanesoctocog alfa prophylaxis was associated with significantly lower rates of any, treated, and joint bleeds and improved joint health compared with emicizumab in patients with severe haemophilia A.
3期XTEND-1试验（NCT04161495）表明，在重度A型血友病患者中，与试验前的凝血因子VIII（FVIII）预防治疗相比，艾美赛珠单抗预防治疗在预防出血方面效果更佳。本研究的目的是间接比较艾美赛珠单抗与非凝血因子替代疗法艾美赛珠单抗在无抑制物的重度A型血友病青少年和成年患者中的疗效。
进行了一项系统的文献综述，以确定艾美赛珠单抗的3期试验。采用匹配调整间接比较法，比较艾美赛珠单抗与艾美赛珠单抗在任何、治疗、关节和自发性出血方面的年化出血率（ABR），以及关节健康状况（使用血友病关节健康评分[HJHS]进行测量）。使用随机效应荟萃分析汇总不同艾美赛珠单抗方案的估计效应，以评估艾美赛珠单抗与艾美赛珠单抗在出血结局方面的总体差异。
纳入了一项艾美赛珠单抗试验（HAVEN 3），该试验研究了三种给药方案。在荟萃分析中，与接受过预防治疗或按需治疗的无抑制物患者中每1周一次（Q1W）的艾美赛珠单抗相比，每周一次（Q1W）的艾美赛珠单抗在任何出血（发生率比[95%CI]0.33[0.20；0.53]）、任何治疗性出血（0.49[0.30；0.80]）和治疗性关节出血（0.51[0.28；0.91]）方面的年化出血率显著更低。与每1周一次或每2周一次的艾美赛珠单抗相比，每周一次（Q1W）的艾美赛珠单抗在HJHS关节评分（平均差异[95%CI]-2.06[-3.97；-0.14]）和总分（-2.37[-4.36；-0.39]）方面从基线的改善也显著更好。
在重度A型血友病患者中，与艾美赛珠单抗相比，艾美赛珠单抗预防治疗与任何出血、治疗性出血和关节出血的发生率显著降低以及关节健康状况改善相关。
