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• W3082058144 abstract "Sickle cell anemia (SCA) is a common and devastating inherited blood disorder, affecting millions of people across the world. Without treatment, SCA results in tremendous morbidity and early mortality. Hydroxyurea is the primary and most well‐established pharmacologic therapy with proven benefits to ameliorate the clinical course of SCA, primarily due to its ability to increase the expression of fetal hemoglobin (HbF), which prevents sickling of red blood cells. The optimal induction of HbF depends upon selection and maintenance of the proper dose that maximizes benefits and minimizes toxicity. Due to the significant interpatient variability in hydroxyurea pharmacokinetics, pharmacodynamics, and dosing, most patients treated with hydroxyurea receive suboptimal doses and have only modest treatment responses. Recognizing this variability, using a precision medicine approach, we developed and prospectively evaluated an individualized dosing model for children with SCA, designed to optimize the hydroxyurea dose and clinical response. We utilize novel laboratory methods and a sparse sampling strategy requiring only 10 μL of blood collected 15 minutes, 60 minutes, and 180 minutes after a test dose. We use Bayesian adaptive control to estimate hydroxyurea exposure and to select an individual, optimal starting dose. This dosing model has resulted in HbF responses >30–40%, levels beyond what is achieved with traditional weight‐based dosing and trial and error dose escalation. This hydroxyurea dosing strategy, if widely implemented, has the potential to change the treatment paradigm of hydroxyurea therapy and improve outcomes for the millions of patients with SCA across the world." @default.
• W3082058144 created "2020-09-08" @default.
• W3082058144 creator A5017286562 @default.
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• W3082058144 date "2020-10-08" @default.
• W3082058144 modified "2023-10-05" @default.
• W3082058144 title "Changing the Clinical Paradigm of Hydroxyurea Treatment for Sickle Cell Anemia Through Precision Medicine" @default.
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• W3082058144 doi "https://doi.org/10.1002/cpt.2028" @default.
• W3082058144 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7902468" @default.
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