Disparities Between Guideline Recommendations, Implementation of Pharmacokinetic Dosing for Bleeding Disorders

Researchers identified 10 topics that highlight barriers and facilitators for the implementation of pharmacokinetic (PK)-guided dosing in clinical practice. The review findings were published in Blood Reviews. 

“Clinical guidelines and expert groups recommend the use of [PK]-guided dosing of factor replacement therapy for the treatment of bleeding disorders, especially for patients with hemophilia,” explained researchers. 

This scoping review identified 110 articles describing PK-guided dosing in patients with bleeding disorders, mainly hemophilia A. The findings were categorized into 2 overarching themes—efficacy and feasibility—and each theme had 5 topics associated with it.

The efficacy of PK-guided dosing was a key topic discussed in the review. While some studies reported positive outcomes, such as a reduction in factor consumption and lower hospitalization rates, contradictory results were found in other studies. Some studies showed no difference in factor consumption compared to standard dosing, while others reported an increase in factor consumption after switching to PK-guided therapy. 

“These contradictions highlight the need for future research to elucidate current ambiguities,” researchers said.

The feasibility of implementing PK-guided dosing was another important theme discussed. Cost reduction was identified as a facilitator for implementation, as PK-guided dosing has been associated with a potential decrease in factor consumption. 

Several studies reported dose reduction ranging from 7% to 31% with PK-guided dosing, compared to standard prophylaxis. Additionally, fewer consultations and hospitalizations were observed during PK-guidance. 

However, the suggestion that PK-guided dosing reduces factor consumption remains controversial, as some studies did not find any differences or even reported an increase in factor consumption, researchers said. The review also highlighted the lack of studies considering the cost of sampling and PK calculations, and the under-reporting of cost-effectiveness in hemophilia B.

Future studies should focus on standardizing dosing regimens and targeted trough levels under PK guidance to provide more consistent and reliable results, researchers advised. The cost of sampling and PK calculations also should be considered to evaluate the overall cost-effectiveness of PK-guided dosing. 

Furthermore, there is a need to explore the feasibility and effectiveness of PK-guided dosing in other bleeding disorders beyond hemophilia A, such as hemophilia B, researchers said.

“The contradicting results, especially with regards to the efficacy of PK-guided dosing, highlight the knowledge gaps and the necessity for more research on implementation strategies,” researchers concluded.

Reference:
Goedhart TMHJ, Janssen A, Mathôt RAA, Cnossen MH; OPTI-CLOT Study Group and SYMPHONY Consortium. The road to implementation of pharmacokinetic-guided dosing of factor replacement therapy in hemophilia and allied bleeding disorders. Identifying knowledge gaps by mapping barriers and facilitators. Blood Rev. 2023;101098. doi:10.1016/j.blre.2023.101098