The Impact of Pharmacokinetic-Guided Prophylaxis on Clinical Outcomes and Healthcare Resource Utilization in Hemophilia A Patients: Real-World Evidence from the CHESS II Study

Abstract

Background

Using a pharmacokinetic (PK)-guided approach to personalize the dose and frequency of prophylactic treatment can help achieve and maintain targeted factor VIII (FVIII) trough levels in patients with hemophilia A.

Objective

Investigate clinical and healthcare resource use outcomes in patients with hemophilia A treated with or without PK-guided prophylaxis using data from the Cost of Haemophilia in Europe: A Socioeconomic Survey (CHESS) II database.

Methods

CHESS II was a cross-sectional, retrospective, burden-of-illness study incorporating data from eight European countries. Patients were eligible for this analysis if they were male, ≥18 years of age, and diagnosed with congenital hemophilia A of any severity. The clinical endpoints included annualized bleeding rate (ABR), presence and number of problem/target joints, and occurrence of joint surgeries. Healthcare resource utilization endpoints included the number of hematologist consultations and bleed-related hospitalizations or emergency department admissions. Data from November 2018 to October 2020 were included and were stratified according to treatment regimen and use of PK-guided dosing.

Results

Altogether, 281 patients on prophylaxis had available FVIII trough level data. Mean (SD) age was 35.7 (13.8) years. A specific FVIII trough level was targeted in 120 (42.7%) patients and 47 (39.2%) received PK-guided dosing. Patients receiving PK-guided dosing had a mean (SD) ABR of 2.8 (2.1) and target joint number of 0.5 (0.7), compared with 3.9 (2.7) and 0.9 (1.4), respectively, for patients receiving non–PK-guided treatment. The mean (SD) number of hematologist consultations was 7.1 (5.3) for patients receiving PK-guided dosing versus 10.7 (5.7) for those who were not. A higher proportion of patients in the non–PK-guided group required hospitalization during their lifetime compared with the PK-guided group.

Conclusion

This analysis of real-world data suggests that PK-guided dosing for prophylaxis has a beneficial impact on clinical and healthcare resource utilization outcomes in patients with hemophilia A.

Keywords:

• hemophilia A
• recombinant factor VIII
• prophylaxis
• PK-guided dosing
• personalized treatment
• CHESS II

Abbreviations

ABR, annualized bleeding rate; CHESS, Cost of Haemophilia in Europe: A Socioeconomic Survey; EHL, extended half-life; FVIII, factor VIII; ICU, intensive care unit; OLS, ordinary least-squares regression; PCC, Pearson’s correlation coefficient; PK, pharmacokinetic; PPIE, Patient and Public Involvement and Engagement; SD, standard deviation.

Data Sharing Statement

The datasets generated and/or analyzed during the current study are held under license by the University of Chester and are not publicly available. Upon reasonable request, and subject to review, the corresponding author will provide the analyses that support the findings of this research. Subject to certain criteria, conditions, and exceptions, access to the related data for researchers who provide a methodologically sound proposal may be considered by data owners HCD Economics and the University of Chester. The data will be provided after its de-identification, in compliance with applicable privacy laws, data protection, and requirements for consent and anonymization.

Ethics Approval and Informed Consent

All patient participants provided informed consent and the study protocol was approved by the Research Ethics Sub Committee of the Faculty of Health and Social care within the University of Chester. The approval stipulated that the study was to be carried out in correspondence with regional and relevant guidelines.

Acknowledgments

Under the direction of the authors, medical writing and editorial support was provided by Laura Harrison, PhD, of Excel Medical Affairs (Fairfield, CT, USA) and was funded by Takeda Development Center Americas, Inc., Lexington, MA, USA. The abstract of this paper was presented at ISTH 2021 as a poster presentation with interim findings. The poster’s abstract was published in Special Issue: Abstracts of the ISTH 2021 Virtual Congress of the International Society of Thrombosis and Haemostasis, July 17–21, 2021 in Research and Practice in Thrombosis and Haemostasis: https://onlinelibrary.wiley.com/doi/10.1002/rth2.12589.

Author Contributions

All authors contributed to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

EFG, TB, and JOH are employees of HCD Economics. SXS is an employee of Takeda Development Center Americas, Inc. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was funded by Takeda Development Center Americas, Inc., Lexington, MA, USA. Takeda were involved in study conception, design, and interpretation of results, as well as drafting and submission of the manuscript.