Abstract Number: PB0991
Meeting: ISTH 2020 Congress
Background: Pharmacokinetic (PK)-guided treatment can be applied to individualize replacement therapy in hemophilia patients, as inter-individual differences in PK parameters influence coagulation factor VIII (FVIII) and factor IX (FIX) activity levels. Worldwide introduction of extended half-life (EHL) concentrates has further underlined this. Moreover, PK-guided dosing has the potential to increase insight into PK-pharmacodynamics (PK-PD) of factor concentrates in bleeding disorders e.g. associations between factor levels, bleeding (risk) and patient activity patterns.
Aims: Investigate the reliability and feasibility of PK-guided prophylactic dosing of factor concentrates in hemophilia A and B patients.
Methods: On May 1st 2019, a non-randomized, prospective observational cohort study was initiated for hemophilia A and B patients of all ages on prophylaxis, both standard half-life (SHL) and EHL concentrates (Netherlands trial Register:7523). Medical Ethical Committee approval was obtained. After informed consent, individual PK profiling is performed and patients start (iterative) PK-guided treatment for 36 weeks. The predicted dosing regimen is validated by a minimum of four factor levels. Detailed information on doses, blood sampling, bleeding events, activity patterns, expectations before and experiences after initiation of PK-guided dosing are documented.
Results: The first 15 patients have been included. Important results and conclusions will be presented, addressing current knowledge gaps in replacement therapy using SHL and novel EHL factor concentrates. Clinical dilemma’s and challenges will be discussed and dwelled upon and include unexpected PK parameters, limitations of population PK models as provided by clinical trials, factor targeting during sporting activities and factor assay discrepancies which influence PK-guided dosing and clinical decision making.
Conclusions: The prospective OPTI-CLOT TARGET study, which implements PK-guided prophylaxis with factor concentrates, will provide new insights on how to manage prophylactic replacement therapy more optimally. Moreover, it may lead to a better understanding of the relationships between factor levels, bleeding (risk) and patient activity patterns, in order to optimize personalized treatment.
To cite this abstract in AMA style:Goedhart MHJ, Bukkems LH, Coppens M, Fijnvandraat K, Meijer K, Leebeek FWG, Mathôt RAA, Cnossen MH, for the OPTI-CLOT Study Group . How to Treat Hemophilia A and B Patients Prophylactically on Standard and Extended Half-Life Factor Concentrates under Pharmacokinetic (PK) Guidance? First Experiences of a Prospective Cohort Study (OPTI-CLOT TARGET) [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/how-to-treat-hemophilia-a-and-b-patients-prophylactically-on-standard-and-extended-half-life-factor-concentrates-under-pharmacokinetic-pk-guidance-first-experiences-of-a-prospective-cohort-study-o/. Accessed November 30, 2021.
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