Model-Informed Abatacept Dose Recommendation in Pediatric Patients With Acute Graft Versus Host Disease.

This study uses a population pharmacokinetic (PPK) approach to provide abatacept dosing recommendations in pediatric patients 2 to < 6 years of age receiving unrelated donor hematopoietic stem cell transplantation (HSCT) due to hematologic malignancies (HMs), for the prophylaxis of acute graft-versus-host disease (aGVHD). An intermediate PPK model was developed and refined to include data from 904 patients aged 2-17 years with juvenile idiopathic arthritis administered with subcutaneous abatacept. Then, PK simulations were performed using the final PPK model for virtual pediatric patients aged 2 to < 6 years administered with either intravenous abatacept, fixed abatacept doses, or loading doses followed by maintenance dosing. The final model characterized abatacept exposure well using a linear, two-compartment model including absorption parameters (KA and F1), and generated parameter estimates comparable to previously published models. Further simulations of abatacept exposure in 10,000 virtual patients aged 2 to <6 years revealed that a 15-mg/kg loading dose followed by 12-mg/kg maintenance doses achieved exposure levels similar to adults at risk of aGVHD, and therefore was selected for these patients. Additionally, an exposure-response (E-R) safety analysis in patients aged ≥6 years with HMs undergoing HSCT showed no significant relationship between abatacept exposure and occurrence of infection, confirming the safety of abatacept in these patients. The recommended dosing regimen for pediatric patients aged 2 to <6 years at risk of aGVHD is a 15-mg/kg loading dose on Day -1, followed by 12 mg/kg for the remaining doses on Days 5, 14, and 28.