Efficacy of rFIXFc versus N9-GP Prophylaxis in Patients with Hemophilia B: Matching-Adjusted Indirect Comparison of B-LONG and PARADIGM 2 Trials.

IF 2.1 Q3 HEMATOLOGY
Maria Elisa Mancuso, Daniel Eriksson, Aletta Falk, Zalmai Hakimi, Piotr Wojciechowski, Marlena Wdowiak, Robert Klamroth
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引用次数: 0

Abstract

Purpose: For patients with hemophilia B, extended half-life factor IX (FIX) products are available for prophylaxis and for treating bleeds. Different methods are used to extend the half-lives of recombinant FIX Fc fusion protein (rFIXFc) and nonacog beta pegol (N9-GP). This affects their biodistribution and plasma FIX levels, although differences do not always correlate with clinical outcomes. A matching-adjusted indirect comparison (MAIC) of prophylaxis with rFIXFc and N9-GP was performed, based on licensed dosing in the European Union.

Patients and methods: Combined rFIXFc data from the weekly and individualized interval prophylaxis arms of the B-LONG clinical trial, and N9-GP data from the 40 IU/kg once-weekly prophylaxis arm of PARADIGM 2 were used in a MAIC. Individual patient data for rFIXFc (n=87) were matched to aggregated data for N9-GP (n=29). Estimated annualized bleeding rates (ABRs) for rFIXFc were recalculated using a Poisson regression model with adjustment for over-dispersion, and compared with ABRs reported for N9-GP, using incidence rate ratios (IRRs) with 95% confidence interval (CI).

Results: There was no evidence of significant differences in estimated ABRs between prophylaxis with rFIXFc and N9-GP. Analysis of pooled rFIXFc weekly and interval-adjusted dosing compared with N9-GP 40 IU/kg once weekly produced estimated ABRs of 2.59 versus 2.51 (IRR 1.03; 95% CI 0.56-1.89), as well as 1.34 versus 1.22 (IRR 1.10; 95% CI 0.42-2.91) and 1.13 versus 1.29 (IRR 0.88; 95% CI 0.47-1.63) for overall, spontaneous, and traumatic bleeding events, respectively.

Conclusion: The study did not reveal any significant differences in the efficacy of rFIXFc and N9-GP prophylaxis. Given differences in trough levels (rFIXFc dosing was targeted to achieve a trough 1-3 IU/dL above baseline versus a reported estimated N9-GP mean trough of 27.3 IU/dL), interpreting plasma FIX levels as potential surrogate efficacy markers requires consideration of compound-specific pharmacokinetic profiles.

Abstract Image

Abstract Image

rFIXFc与N9-GP预防在B型血友病患者中的疗效:B- long和范式2试验的匹配调整间接比较
目的:对于B型血友病患者,延长半衰期因子IX (FIX)产品可用于预防和治疗出血。采用不同的方法延长重组FIXFc融合蛋白(rFIXFc)和nonacog beta pegol (N9-GP)的半衰期。这影响了它们的生物分布和血浆FIX水平,尽管差异并不总是与临床结果相关。基于欧盟许可剂量,对rFIXFc和N9-GP的预防进行了匹配调整间接比较(MAIC)。患者和方法:综合rFIXFc数据来自B-LONG临床试验的每周和个体化间隔预防组,N9-GP数据来自范式2的每周40 IU/kg预防组。rFIXFc的个体患者数据(n=87)与N9-GP的汇总数据(n=29)相匹配。使用泊松回归模型重新计算rFIXFc的估计年化出血率(ABRs),并使用95%可信区间(CI)的发生率比(IRRs)与N9-GP报告的ABRs进行比较。结果:没有证据表明rFIXFc预防和N9-GP预防之间的估计abr有显著差异。将rFIXFc每周一次和间隔调整剂量与N9-GP每周一次40 IU/kg相比进行分析,估计abr为2.59对2.51 (IRR 1.03;95% CI 0.56-1.89),以及1.34 vs 1.22 (IRR 1.10;95% CI 0.42-2.91)和1.13对1.29 (IRR 0.88;95% CI 0.47-1.63)分别用于整体、自发性和外伤性出血事件。结论:本研究未发现rFIXFc和N9-GP预防的疗效有显著差异。鉴于波谷水平的差异(rFIXFc剂量的目标是达到高于基线的波谷1-3 IU/dL,而据报道估计N9-GP平均波谷为27.3 IU/dL),解释血浆FIX水平作为潜在的替代疗效标志物需要考虑化合物特异性药代动力学特征。
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来源期刊
CiteScore
3.50
自引率
0.00%
发文量
94
审稿时长
16 weeks
期刊介绍: The Journal of Blood Medicine is an international, peer-reviewed, open access, online journal publishing laboratory, experimental and clinical aspects of all topics pertaining to blood based medicine including but not limited to: Transfusion Medicine (blood components, stem cell transplantation, apheresis, gene based therapeutics), Blood collection, Donor issues, Transmittable diseases, and Blood banking logistics, Immunohematology, Artificial and alternative blood based therapeutics, Hematology including disorders/pathology related to leukocytes/immunology, red cells, platelets and hemostasis, Biotechnology/nanotechnology of blood related medicine, Legal aspects of blood medicine, Historical perspectives. Original research, short reports, reviews, case reports and commentaries are invited.
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