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

Rui Zhong1,2, Kelly Maxwell3, Julie Passarell3

  • 1Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Journal of Clinical Pharmacology
|February 13, 2026
PubMed

Insights

This study recommends a 15-mg/kg loading dose followed by 12-mg/kg maintenance doses of abatacept for pediatric patients aged 2 to <6 years undergoing hematopoietic stem cell transplantation to prevent acute graft-versus-host disease (aGVHD). This regimen ensures safe and effective abatacept exposure.

Area of Science:

  • Pharmacology and Therapeutics
  • Pediatric Hematology
  • Immunology

Background:

  • Acute graft-versus-host disease (aGVHD) is a significant complication following hematopoietic stem cell transplantation (HSCT).
  • Abatacept is utilized for aGVHD prophylaxis, but optimal dosing in young pediatric patients requires definition.
  • Hematologic malignancies (HMs) are common indications for HSCT in pediatric populations.

Purpose of the Study:

  • To establish population pharmacokinetic (PPK) models for abatacept in pediatric patients.
  • To determine optimal abatacept dosing regimens for children aged 2 to <6 years undergoing HSCT for HMs to prevent aGVHD.
  • To evaluate the safety of abatacept exposure in this vulnerable population.

Main Methods:

  • Developed and refined an intermediate PPK model using data from 904 pediatric patients (2-17 years) with juvenile idiopathic arthritis.
  • Conducted PK simulations with the final PPK model for virtual pediatric patients (2 to <6 years) under various dosing scenarios.
  • Performed an exposure-response (E-R) safety analysis in patients aged ≥6 years with HMs undergoing HSCT.

Main Results:

  • The final PPK model characterized abatacept exposure using a linear, two-compartment model with comparable parameter estimates to prior studies.
  • Simulations indicated that a 15-mg/kg loading dose followed by 12-mg/kg maintenance doses achieved adult-like exposure levels in virtual pediatric patients (2 to <6 years).
  • The E-R safety analysis demonstrated no significant association between abatacept exposure and infection occurrence in older pediatric HSCT patients.

Conclusions:

  • A recommended dosing regimen of a 15-mg/kg loading dose on Day -1, followed by 12 mg/kg on Days 5, 14, and 28, is proposed for pediatric patients aged 2 to <6 years at risk of aGVHD.
  • This regimen is predicted to provide safe and effective abatacept exposure for aGVHD prophylaxis in this age group.
  • The study confirms the safety profile of abatacept concerning infection risk in pediatric HSCT patients.

Keywords:
abataceptgraft‐versus‐host diseasepediatric dose selectionpopulation pharmacokinetics

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