Efficacy, Safety, and Population Pharmacokinetics of Eltrombopag in Children with Different Severities of Aplastic Anemia

Abstract Eltrombopag was approved as a first‐line treatment for patients older than 2 years old with severe aplastic anemia (SAA). However, data on eltrombopag in children with different types of aplastic anemia (AA), especially non‐severe AA (NSAA), are limited. We performed a prospective, single‐arm, and observational study to investigate eltrombopag's efficacy, safety, and pharmacokinetics in children with NSAA, SAA, and very severe AA (VSAA). The efficacy and safety were assessed every 3 months. The population pharmacokinetic (PPK) model was used to depict the pharmacokinetic profile of eltrombopag. Twenty‐three AA children with an average age of 7.9 (range of 3.0‐14.0) years were enrolled. The response (complete and partial response) rate was 12.5%, 50.0%, and 100.0% after 3, 6, and 12 months in patients with NSAA. For patients with SAA and VSAA, these response rates were 46.7%, 61.5%, and 87.5%. Hepatotoxicity occurred in one patient. Fifty‐three blood samples were used to build the PPK model. Body weight was the only covariate for apparent clearance (CL/F) and volume of distribution. The allele‐T carrier of adenosine triphosphate‐binding cassette transporter G2 was found to increase eltrombopag's clearance. However, when normalized by weight, the clearance between the wild‐type and variant showed no statistical difference. In patients with response, children with NSAA exhibited lower area under the curve from time zero to infinity, higher CL/F, and higher weight‐adjusted CL/F than those with SAA or VSAA. However, the differences were not statistically significant. The results may support further individualized treatment of eltrombopag in children with AA.