We would like to express our gratitude to Dr. Huang for his interest and commentary on our publication, “Cost-Effectiveness Analysis of Pharmacokinetic-Guided Prophylaxis Versus Standard Prophylaxis in Adults with Severe Hemophilia A in China” [1]. We hope the following information will be useful in addressing his questions and comments.
The target patients in our study were Chinese adult patients with hemophilia A, and we need to set some baseline parameters to conduct model simulations. Chen et al.’s study [2] includes 35 adult patients with severe hemophilia A, a target population that is consistent with our study, and their study also reports some parameters that are needed for our studies. Hemophilia is a rare disease; it is hard to include plenty of patients in a rare disease study. Other studies [3] mentioned by Dr. Huang may have a greater focus on pediatric patients, which is different from the target population in our study. And the sample size of these studies is also limited, ranging from 15 to 79 patients [4–6].
There are several types of pharmacokinetic (PK) software available to calculate PK parameters and guide dose adjustment. As far as we know, the PK tool WAPPS-Hemo is mainly used in scientific research [7] myPKFiT is a medical device that calculates the prophylactic dose for ADVATE, which was approved by the National Medical Products Administration (NMPA) in 2020 and has a clear recommended dose. In the design of our study, we set the minimum injection dose at 10 IU/KG according to the instructions of myPKFiT. Additionally, this study was limited to ADVATE owing to the instructions of myPKFiT. Perhaps in the future, more studies will be conducted using different factor VIII (FVIII) levels.
As Dr. Huang mentioned, a higher target trough FVIII level could decrease the median annual bleeding rate to zero, and zero bleeding is the ideal goal for patients with hemophilia A. However, based on the clinical practice in China, guidelines for the management of hemophilia in China (2021) [8] show that the standard for trough level in prophylactic treatment is set at 1% (1 IU/dL). Meanwhile, Chinese expert consensus on PK-guided treatment for hemophilia A [7] mentions that “1% is the basic trough level”, and for patients receiving prophylactic treatment, experts recommend that PK analysis should be conducted to estimate if the trough level reaches 1%. Therefore, from the perspective of China, we set the 1 IU/dL as the minimum target trough level in this study.
The study conducted by Iannazzo et al. [9] was also a cost-effectiveness study that used PK parameters to calculate the results. In that study, the age and weight were set by using Austrian patients’ characteristics (median age 27.8 years; median weight 73.7 kg), which is the difference between the two studies. But the recombinant FVIII pharmacokinetic-driven prophylaxis of both studies was based on the same pharmacokinetic model; more details can be found in Björkman et al. [10].
Acknowledgements
Takeda Pharmaceutical Company Limited has provided the scientific review of the response letter.
Authorship
Both named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and gave their approval for this version to be published.
Author Contributions
Congling Gu drafted the first version of the letter. Yi Han carried out critical intellectual revision. Both authors read and approved the final manuscript.
Funding
No funding or sponsorship was received for this study or publication of this article.
Declarations
Conflict of Interest
Congling Gu is employee of Takeda International Trading Co. Ltd, Beijing, China. Yi Han has nothing to disclose.
Ethical Approval
This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
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