Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Feb 6;4(2):326-333.
doi: 10.1002/rth2.12305. eCollection 2020 Feb.

Pharmacokinetic-tailored approach to hemophilia prophylaxis: Medical decision making and outcomes

Stacy E Croteau  1 , Allison P Wheeler  2 , Osman Khan  3 , Kristina M Haley  4 , Alexandra J Borst  5 , Susan Lattimore  4 , Cindy H T Yeung  6 , Alfonso Iorio  6   7
Affiliations

Pharmacokinetic-tailored approach to hemophilia prophylaxis: Medical decision making and outcomes

Stacy E Croteau et al. Res Pract Thromb Haemost. .

Abstract

Background: Clinical application of population pharmacokinetics (popPK) is of increasing interest to patients with hemophilia, providers, and payers. Routine use of popPK profiles in factor replacement prophylaxis decision making has the potential to maintain or improve efficacy and reduce product consumption.

Aim: To investigate the feasibility of implementation and longitudinal assessment of pharmacokinetic (PK)-tailored prophylaxis in routine clinical practice for hemophilia A and to describe factors that influence decision making for prescribed hemophilia prophylaxis.

Methods: This longitudinal, multicenter, prospective feasibility study of children and adults with hemophilia A without inhibitors used the Web Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) to generate PK profiles. Assessments over 12 weeks captured data on prescribed prophylaxis, popPK tool use, provider decision making, and patient-reported outcomes.

Results: Eighteen participants aged 6 to 39 years enrolled; half used extended half-life concentrates. Patient interest in their PK centered on general curiosity followed by a desire for participation in physical activity and decrease in infusion frequency. Providers used the WAPPS clinical calculator feature to simulate prophylaxis regimens under different dose, infusion, and trough conditions. Most targeted troughs were 1 to 3 IU/dL. The feasibility assessment demonstrated challenges with patient recruitment; however, the majority of participants successfully completed study assessments meeting feasibility targets.

Conclusion: A larger-scale study powered to evaluate the impact of PK-tailored prophylaxis on clinical and patient-reported outcomes is feasible with study design modifications to support increased recruitment rate. Shared decision making incorporating patient and provider goals is important and facilitated by regimen simulations with the clinical calculator.

Keywords: decision making; factor VIII; feasibility studies; half‐life; hemophilia A; pharmacokinetics.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Patient and provider reported factors contributing to their interest in a PK profile. FVIII, factor VIII; PK, pharmacokinetics.
Figure 2
Figure 2
Rank of provider‐reported factors contributing to their decision making for prophylaxis. FVIII, factor VIII.
See this image and copyright information in PMC

References

    1. Iorio A. Using pharmacokinetics to individualize hemophilia therapy. Hematology. 2017;2017:595–604. - PMC - PubMed
    1. Hazendonk H, van Moort I, Mathot RAA, Fijnvandraat K, Leebeek FWG, Collins PW, et al. Setting the stage for individualized therapy in hemophilia: What role can pharmacokinetics play? Blood Rev. 2018;32:265–71. - PubMed
    1. Chen SL. Economic costs of hemophilia and the impact of prophylactic treatment on patient management. Am J Manag Care. 2016;22:s126–s133. - PubMed
    1. Tegenge MA, Yang H, Forshee RA. Predicting dose sparing benefit and bleeding risk of pharmacokinetic‐based personalized prophylactic dosing of factor VIII products. Haemophilia. 2017;23:705–11. - PubMed
    1. Oldenburg J. Optimal treatment strategies for hemophilia: achievements and limitations of current prophylactic regimens. Blood. 2015;125:2038–44. - PubMed