Abstract
IMPORTANCE: Eltrombopag has been recommended for pediatric immune thrombocytopenia (ITP). Response and adverse drug reactions (ADRs) varied widely between individuals, even at the same dose of eltrombopag. The appropriate eltrombopag concentration in ITP has not been reported. OBJECTIVE: This study aims to explore the appropriate eltrombopag concentration in pediatric ITP. METHODS: This was a single-center, prospective cohort study. Children diagnosed with refractory persistent/chronic ITP and platelet count < 30×10(9)/L were treated with eltrombopag and followed up for at least 2 months. Concentration was detected by high-performance liquid chromatography-mass spectrometry at least 2 weeks after eltrombopag. The clinical characteristics-concentration, concentration-response, and concentration-ADRs were analyzed. RESULTS: A total of 30 patients were enrolled, comprising 13 males and 17 females, with a median age of 72 (45‒94) months. The median dose and concentration were 1.39 (1.09‒1.56) mg/kg and 2.70 (2.25‒4.13) mg/L, respectively. Of the enrolled patients, 14 responded to treatment, whereas 16 did not. Additionally, five experienced adverse drug reactions. No linear correlation was observed between eltrombopag concentration and clinical characteristics. The concentration was lower in the response group than in the nonresponse group, but there was no significant difference (t = 0.755, P = 0.457). Patients who experienced ADRs had a higher concentration than those without ADRs (t = 2.538, P = 0.017). The area under the receiver operating characteristic curve of ADRs was 0.78 (95% confidence interval: 0.56‒1.00). Youden's index identified the cutoff point as 4.33 mg/L, with a sensitivity of 88% and a specificity of 60%. Logistic regression analysis demonstrated that a higher platelet count before eltrombopag predicted a favorable response. INTERPRETATION: Eltrombopag proves efficacious and well-tolerated for treating pediatric ITP. However, prolonged and high-dose administration may increase the likelihood of ADRs. Thus, examining the appropriate eltrombopag concentration assists in directing individualized management of pediatric ITP.