39 - SAFE AND EFFECTIVE ANTICOAGULANT: RIVAROXABAN IN THE MANAGEMENT OF CHILDREN WITH GIANT CORONARY ANEURYSMS AFTER KAWASAKI DISEASE

Background: Rivaroxaban is a potential substitute for warfarin in pediatric patients with giant coronary artery aneurysm (GCAA) after KD. However, clinical data on rivaroxaban for this population are limited. We aimed to describe the case series of rivaroxaban off-label use, as well as the study of model- and clinical evidence-informed precision dosing in Chinese pediatric patients.

Methods: This prospective case series included patients diagnosed with GCAA after acute stage of KD who were recommended to receive long-term anticoagulant treatment between January to October in 2023. Rivaroxaban population pharmacokinetic models were extrapolated to Chinese children, incorporating with existing knowledge. Dosing regimens were proposed by model simulation and cross-validated by clinical evidence from the case series.

Results: Six patients received rivaroxaban with a median (range) rivaroxaban treatment duration of 185.5 (110, 261) days. (median [range] age, 14.6 (4.7, 130.8) months; median [range] weight, 9.9 [6.6, 33] kg;3 boys [50%]). No coronary artery thrombosis or major bleeding were observed. Four clinical relevant non-major bleedings and one minor bleeding occurred in three patients (50%). Because of bleeding events and/or significantly prolonged prothrombin time and activated partial thromboplastin time, six dose adjustments were made in four patients (66%) to balance thrombosis and bleeding risks. Instead of the recommended dosages from the 20 mg-equivalent dosing regimen, patients remained relatively stable at a reduced dosage of rivaroxaban. Two patients (33%) received a consistent, reduced dose and discontinued rivaroxaban until CAA regression. Therefore, the model- and clinical evidence-informed precision dosing strategy was applied to dose finding. Two published rivaroxaban population pharmacokinetic models were separately extrapolated to Chinese pediatric population. Dosing regimens proposed from the simulation of two models demonstrated great consistency. Calibrated with clinical evidence from the case series and real-world clinical practice, the 15 mg-equivalent, age- and bodyweight- adjusted dosing regimen was proposed.

Conclusion: Rivaroxaban is a safe and effective anticoagulant in the management of Chinese pediatric patients with GCAA after KD, but dose optimization is necessary for Chinese, even Asian, pediatric patients. For better use of limited clinical evidence, we adopted the model- informed precision dosing strategy to facilitate dose selection in clinical practice, and proposed the 15 mg-equivalent dosing regimen for Chinese pediatric patients with GCAA after KD. Future studies are needed to assess the safety and efficacy of the optimized dosing regimen before clinical application.