Critical Overview of Clinical Studies on EHL FVIII Preparations
An international team of experts recently published a comprehensive work evaluating the methodology used in clinical trials of various extended half-life (EHL) factor VIII (FVIII) products. Their work does not directly compare the individual products but aims to assess the results of key registration clinical trials from the perspective of the hematologist and everyday clinical practice.
Similar and Different Aspects of Clinical Study Design
Overall, 900 pediatric, adolescent, and adult patients were included in eight registration studies. In addition to several similarities displayed by the individual studies, some significant differences were also noted. Important methodological differences include the study duration and its extended follow-up, the definition of the control group, intervals for prophylactic doses, the method of randomization, etc. The authors conclude that the individual studies cannot be directly compared, and a meta-analysis cannot be performed. Furthermore, clinical studies directly comparing (head-to-head) the efficacy and safety of the individual preparations are lacking in practice.
Personalizing Care for Patients with Hemophilia A
Despite the present differences, the study results clearly show that EHL FVIII preparations exhibit consistent efficacy in prophylactic regimens across varying dosing intervals. The extended biological half-life allows for longer dosing intervals and better adaptation of treatment considering the individual bleeding phenotype and lifestyle.
The ability to achieve higher trough levels of FVIII also contributes to individualized treatment. Current data indicates that commonly recommended FVIII trough levels in prophylactic treatment (> 1–3%) may not entirely prevent bleeding episodes. While there are patients who do not bleed even when their trough levels are < 1% for a shorter period, the current treatment goal is to support social and physical activities by achieving higher trough levels (> 3–5%) ideally without increasing the number of infusions.
However, studies with EHL FVIII have to some extent provided a limited view on how effectively different products maintain FVIII trough levels during prophylaxis. For example, only a few studies enabled the individualization of dosing intervals according to patient needs. There is also a lack of data from real clinical practice, which could generate algorithms for selecting the right product and optimal dosing regimen for each patient.
Conclusion
The methodology and results of registration clinical trials comprehensively compared in the cited work offer valuable information that physicians can use to find the optimal treatment regimen for a specific patient. They also highlight uncertainties and knowledge gaps that future clinical research should address.
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Source: Hermans C., Reding M. T., Astermark J. et al. Clinical studies of extended-half-life recombinant FVIII products for prophylaxis in adults and children: a critical review from the physician’s perspective. Crit Rev Oncol Hematol 2022 Jun; 174: 103678, doi: 10.1016/j.critrevonc.2022.103678.
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