|The following article features coverage from the 61st American Society of Hematology Annual Meeting and Exposition. Click here to read more of Hematology Advisor’s conference coverage.|
Bodyweight-adjusted treatment with rivaroxaban was well tolerated by pediatric patients with venous thromboembolism (VTE), according to research presented at the 61st American Society of Hematology (ASH) Annual Meeting in Orlando, Florida.
In the randomized phase 3 EINSTEIN-Jr study (ClinicalTrials.gov Identifier: NCT02234843), researchers evaluated 316 pediatric patients with VTE who received rivaroxaban, which is currently licensed for use in adults but not in children, in either tablet (121 patients) or suspension (195 patients) formulation. Dosage was adjusted for bodyweight, with patients weighing less than 12 kg receiving treatment thrice daily, patients weighing between 12 kg and 30 kg receiving treatment twice daily, and patients weighing 30 kg or more receiving treatment once daily. Total daily dose ranged from 2.4 mg to 20 mg.
Population pharmacokinetic (PK) modeling was used to measure 24-hour area under the plasma concentration-time curve, as well as trough and maximum steady-state plasma concentrations. To assess associations between PK parameters and recurrent VTE, change in thrombus burden at repeat imaging, and incidence of bleeding or adverse events, the researchers developed exposure-response graphs using adult reference ranges. Dose-exposure graphs were developed as well. “Our goal was [for] exposure to be the same in children as in adults,” noted Guy Young, MD, of the University of Southern California Keck School of Medicine in Los Angeles, during his presentation.
Bodyweight-adjusted rivaroxaban treatment regimens led to similar exposure in children as in adults receiving 20 mg rivaroxoban once daily, with the majority of individual PK parameter values falling within the adult reference range.
Two patients experienced symptomatic recurrent VTE. In asymptomatic patients, repeat imaging outcomes improved in 125 patients, normalized in 124, did not change in 16, and deteriorated in 1; the result of repeat imaging was uncertain for the remaining 48 patients. There were no major bleeding events, although 10 patients experienced clinically relevant nonmajor bleeding and 111 patients experienced trivial bleeding.
Once again, PK parameter values fell within the expected reference range irrespective of VTE and bleeding outcome, suggesting exposure was not significantly associated with efficacy, bleeding, or adverse events. No association was found between rivaroxaban formulation and any outcomes.
“Hopefully this will lead to approval and licensure of rivaroxaban for children of all ages,” said Dr Young, “especially of the child-friendly suspension [formulation] that was made for this trial.”
Disclosures: Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
- Young G, Lensing AWA, Monagle P, Male C, Kubitza D. Rivaroxaban for treatment of pediatric venous thromboembolism. An Einstein-Jr phase 3 dose-exposure-response evaluation. Oral presentation at: 61st ASH Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 164.