Pharmacokinetics and Safety of Ustekinumab in Patients with Juvenile Psoriatic Arthritis: Results of the Real-World Ustekinumab Pediatric Opportunistic Pharmacokinetics Study (U-POPS)

乌司奴单抗在幼年银屑病关节炎患者中的药代动力学和安全性:真实世界乌司奴单抗儿科机会性药代动力学研究 (U-POPS) 的结果

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Abstract

INTRODUCTION: The "Ustekinumab Pediatric Opportunistic Pharmacokinetics Study" (U-POPS) was conducted to evaluate the pharmacokinetics (PK) and safety of ustekinumab, an interleukin-12/23p40 antagonist, in patients with juvenile psoriatic arthritis (jPsA) who were already receiving ustekinumab via an opportunistic study design. U-POPS was based on the clinical hypothesis that PK should be similar in jPsA and pediatric psoriasis (PsO) populations to further strengthen the extrapolation paradigm between the two populations. METHODS: This real-world, open-label study enrolled participants 5 to < 18 years old with jPsA or 6 to < 18 years with PsO (internal control) who were on ustekinumab for ≥ 16 weeks and received ≥ 3 doses to ensure steady-state concentrations. Ustekinumab was prescribed by the treating physician and supplied outside of the study; PK samples were collected at intervals during a maximum of 16 weeks. The primary endpoint was the observed serum ustekinumab concentrations, which were compared to model-predicted values from prior PsO PK data. RESULTS: The study included 11 patients with jPsA (mean age, 15.1 years) and 20 with pediatric PsO (mean age, 12.6 years), yielding 100 PK samples. The median ustekinumab dose was 45 mg every 12 weeks. Observed serum ustekinumab concentration-time profiles aligned well with model-predicted concentration-time profiles from pediatric PsO patients. Treatment-emergent adverse events (TEAEs) occurred in 25.8% of patients (jPsA, n = 1; PsO, n = 7) and were consistent with those observed in other ustekinumab studies, with no serious TEAEs reported. CONCLUSIONS: The opportunistic U-POPS study confirmed the existing population PK model for ustekinumab and suggests that ustekinumab exposure and time course are similar between jPsA and pediatric PsO populations, with no new safety concerns. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05252533 (registration date: 02-16-2022); EudraCT Number, 2021-005085-18.

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