重度 A 型血友病出血结局的匹配调整间接比较：比较 valoctocogene roxaparvovec 基因治疗、emicizumab 预防治疗和 FVIII 替代预防治疗。
Matching-adjusted indirect comparison of bleeding outcomes in severe haemophilia A: Comparing valoctocogene roxaparvovec gene therapy, emicizumab prophylaxis, and FVIII replacement prophylaxis.
机构信息
Department of Translational Medicine, Lund University, Lund, Sweden.
Department for Hematology, Oncology and Radiation Physics, Skåne University Hospital, Malmö, Sweden.
出版信息
Haemophilia. 2023 Jul;29(4):1087-1094. doi: 10.1111/hae.14818. Epub 2023 Jun 22.
INTRODUCTION
Head-to-head evaluation of valoctocogene roxaparvovec, the first gene therapy approved for haemophilia A, with emicizumab is not available. Therefore, phase 3 trial data were indirectly compared.
AIM
To compare bleeding rates in trials evaluating 6 × 10 vg/kg valoctocogene roxaparvovec (GENEr8-1; NCT03370913), 1.5 mg/kg emicizumab dosed every week (HAVEN 3; NCT02847637), and FVIII prophylaxis (270-902) in participants with severe haemophilia A (FVIII ≤1 IU/dL).
METHODS
Valoctocogene roxaparvovec versus emicizumab and FVIII prophylaxis as used in 270-902 versus emicizumab cross-trial comparisons were performed using matching-adjusted indirect comparison (MAIC). Individual participant data from GENEr8-1 and 270-902 were weighted to equalise aggregate participant baseline characteristics from HAVEN 3. After MAIC weighting, annualised bleeding rates (ABR) and proportions of participants without bleeds were compared for treated bleeds, all bleeds, treated joint bleeds, and treated spontaneous bleeds.
RESULTS
After MAIC weighting, ABR for all bleeds was statistically significantly lower with valoctocogene roxaparvovec than emicizumab (rate ratio [95% CI], .55 [.33-.93]). Additionally, significantly higher proportions of participants had no treated joint bleeds (odds ratio [95% CI], 2.75 [1.20-6.31]) and no treated bleeds (3.25 [1.53-6.90]) with valoctocogene roxaparvovec versus emicizumab. When compared with the mainly standard half-life FVIII prophylaxis regimens in 270-902, mean ABRs (except for all bleeds) were significantly lower, and significantly higher proportions reported 0 bleeds for all outcomes with emicizumab.
CONCLUSION
Valoctocogene roxaparvovec provided generally lower bleeding rates and higher probability of no bleeds, including treated joint bleeds, than emicizumab. Emicizumab was more effective than FVIII prophylaxis regimens used in 270-902.
简介
目前尚无获批用于治疗 A 型血友病的基因治疗药物 valoctocogene roxaparvovec（商品名：Genocto）与emicizumab 的头对头比较的临床试验数据。因此，本研究采用间接比较的方法对这两种药物的 3 期临床试验数据进行了比较。
目的
比较 6×10 10vg/kg 剂量 valoctocogene roxaparvovec（GENEr8-1；NCT03370913）、1.5mg/kg 剂量 emicizumab 每周 1 次（HAVEN 3；NCT02847637）和重度 A 型血友病（FVIII≤1IU/dL）患者采用 FVIII 预防性治疗（270-902）的出血率。
方法
采用匹配调整间接比较（MAIC）对 GENEr8-1 与 270-902 交叉试验比较中 valoctocogene roxaparvovec 与 emicizumab 及 FVIII 预防性治疗的结果进行分析。从 HAVEN 3 中对 GENEr8-1 和 270-902 的个体参与者数据进行加权，使汇总参与者基线特征在 HAVEN 3 中均衡。MAIC 加权后，比较治疗性出血、所有出血、治疗性关节出血和治疗性自发性出血的年化出血率（ABR）和无出血参与者的比例。
结果
MAIC 加权后，valoctocogene roxaparvovec 治疗的所有出血的 ABR 显著低于 emicizumab（率比[95%CI]，.55[.33-.93]）。此外，valoctocogene roxaparvovec 治疗组的参与者无治疗性关节出血（优势比[95%CI]，2.75[1.20-6.31]）和无治疗性出血（3.25[1.53-6.90]）的比例显著高于 emicizumab 治疗组。与 270-902 中的主要标准半衰期 FVIII 预防性治疗方案相比，除所有出血外，valoctocogene roxaparvovec 治疗组的平均 ABR 显著降低，emicizumab 治疗组所有结局均有更高比例的参与者报告无出血。
结论
valoctocogene roxaparvovec 治疗的出血率总体低于 emicizumab，且包括治疗性关节出血在内的无出血率更高。与 270-902 中的 FVIII 预防性治疗方案相比，emicizumab 更为有效。
Zotero 插件