Sobi, Stockholm, Sweden.
Sobi, Basel, Switzerland.
Adv Ther. 2021 Feb;38(2):1263-1274. doi: 10.1007/s12325-020-01599-1. Epub 2020 Dec 30.
Prophylaxis with recombinant factor VIII (rFVIII) is the current standard of care for haemophilia A. Several approaches have been used to extend the half-life of rFVIII to improve prophylaxis outcomes. An indirect comparison of pivotal clinical trial data was performed to evaluate the relative efficacy of two extended half-life therapies approved for the prophylactic treatment of haemophilia A: recombinant FVIII-IgG Fc domain fusion protein (rFVIIIFc) and pegylated rFVIII (BAY 94-9027).
Matching-adjusted indirect comparison (MAIC) was conducted to compare the rFVIIIFc individualised prophylaxis arm of the A-LONG phase III clinical trial (n = 117) and the BAY 94-9027 approved dosing regimens of the PROTECT VIII phase II/III study (n = 110). Following matching for baseline characteristics, mean annualised bleeding rate (ABR) and the proportion of patients with zero bleeds were compared for rFVIIIFc and BAY 94-9027. Additional supportive analyses comparing rFVIIIFc individualised prophylaxis and the individual prophylaxis regimens included in the PROTECT VIII group (twice weekly, and every 5 and 7 days [Q5D and Q7D]) were conducted.
Mean ABR was lower in the rFVIIIFc individualised prophylaxis group versus the BAY 94-9027 pooled prophylaxis population (3.0 versus 4.9), providing a clinically relevant and statistically significant difference (mean difference [MD] - 1.9; 95% confidence interval [CI] - 3.5 to - 0.4). A statistically significant difference in ABR was also observed for rFVIIIFc compared with BAY 94-9027 Q7D (3.2 versus 6.4; MD - 3.3; 95% CI - 6.4 to - 0.2). The difference in the proportion of patients with zero bleeds between rFVIIIFc (46.5%) and BAY 94-9027 pooled prophylaxis population (38.2%) was not statistically significant (odds ratio 1.4; 95% CI 0.8 to 2.5).
This indirect treatment comparison indicates a statistically significant and clinically relevant difference in ABR favouring individualised prophylaxis with rFVIIIFc versus BAY 94-9027 prophylaxis. The proportion of patients with zero bleeds was numerically greater with rFVIIIFc treatment but did not achieve statistical significance.
重组因子 VIII（rFVIII）的预防治疗是目前治疗血友病 A 的标准方法。已经采用了几种方法来延长 rFVIII 的半衰期，以改善预防治疗的效果。本研究通过间接比较关键性临床试验数据，评估了两种已批准用于血友病 A 预防性治疗的延长半衰期疗法的相对疗效：重组 FVIII-IgG Fc 结构域融合蛋白（rFVIIIFc）和聚乙二醇化 rFVIII（BAY 94-9027）。
采用匹配调整间接比较（MAIC）比较了 A-LONG Ⅲ期临床试验中 rFVIIIFc 个体化预防治疗组（n=117）和 PROTECT VIII Ⅱ/Ⅲ期研究中 BAY 94-9027 批准剂量方案（n=110）的疗效。在匹配基线特征后，比较 rFVIIIFc 和 BAY 94-9027 组的年平均出血率（ABR）和无出血患者比例。还进行了比较 rFVIIIFc 个体化预防治疗与 PROTECT VIII 组中包括的个体化预防方案（每周 2 次、每 5 天和每 7 天[Q5D 和 Q7D]）的额外支持性分析。
rFVIIIFc 个体化预防治疗组的平均 ABR 低于 BAY 94-9027 汇总预防人群（3.0 比 4.9），差异具有临床意义和统计学意义（平均差值[MD]-1.9；95%置信区间[CI]-3.5 至-0.4）。rFVIIIFc 与 BAY 94-9027 Q7D 相比，ABR 也存在统计学显著差异（3.2 比 6.4；MD-3.3；95% CI-6.4 至-0.2）。rFVIIIFc（46.5%）与 BAY 94-9027 汇总预防人群（38.2%）之间无出血患者比例的差异无统计学意义（比值比 1.4；95% CI 0.8 至 2.5）。
这项间接治疗比较表明，rFVIIIFc 个体化预防治疗与 BAY 94-9027 预防治疗相比，在 ABR 方面具有统计学意义和临床意义的差异。rFVIIIFc 治疗组无出血患者比例更高，但未达到统计学意义。
