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Title: | A prospective controlled, randomized clinical trial of kidney transplant recipients developed personalized tacrolimus dosing using model-based Bayesian Prediction |
Author: | Lloberas Blanch, Núria Grinyó Boira, Josep M. Colom Codina, Helena Vidal Alabró, Anna Fontova, Pere Rigo Bonnin, Raúl Padró i Miquel, Ariadna Bestard Matamoros, Oriol Melilli, Edoardo Montero Pérez, Núria Coloma, Ana Manonelles, Anna Meneghini, Maria Favà Buch, Alexandre Torras Ambròs, Joan Cruzado, Josep Ma. |
Keywords: | Trasplantament renal Estadística bayesiana Immunosupressors Genètica Kidney transplantation Bayesian statistical decision Immunosupressive agents Genetics |
Issue Date: | 1-Oct-2023 |
Publisher: | Elsevier B.V. |
Abstract: | For three decades, tacrolimus (Tac) dose adjustment in clinical practice has been calculated empirically according to the manufacturer’s labeling based on a patient’s body weight. Here, we developed and validated a Population pharmacokinetic (PPK) model including pharmacogenetics (cluster CYP3A4/CYP3A5), age, and hematocrit. Our study aimed to assess the clinical applicability of this PPK model in the achievement of Tac Co (therapeutic trough Tac concentration) compared to the manufacturer’s labelling dosage. A prospective two-arm, randomized, clinical trial was conducted to determine Tac starting and subsequent dose adjustments in 90 kidney transplant recipients. Patients were randomized to a control group with Tac adjustment according to the manufacturer’s labeling or the PPK group adjusted to reach target Co (6-10 ng/ml) after the first steady state (primary endpoint) using a Bayesian prediction model (NONMEM). A significantly higher percentage of patients from the PPK group (54.8%) compared with the control group (20.8%) achieved the therapeutic target fulfilling 30% of the established superiority margin defined. Patients receiving PPK showed significantly less intra-patient variability compared to the control group, reached the Tac Co target sooner (5 days vs 10 days), and required significantly fewer Tac dose modifications compared to the control group within 90 days following kidney transplant. No statistically significant differences occurred in clinical outcomes. Thus, PPK-based Tac dosing offers significant superiority for starting Tac prescription over classical labeling-based dosing according to the body weight, which may optimize Tac-based therapy in the first days following transplantation. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1016/j.kint.2023.06.021 |
It is part of: | Kidney International, 2023, vol. 104, num.4, p. 840-850 |
URI: | http://hdl.handle.net/2445/208350 |
Related resource: | https://doi.org/10.1016/j.kint.2023.06.021 |
ISSN: | 0085-2538 |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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