Pharmacokinetics, Efficacy, and Safety of Upadacitinib in Pediatric Patients With Polyarticular-Course Juvenile Idiopathic Arthritis: An Interim Analysis of an Open-Label, Phase 1 Trial

Arthritis Care Res (Hoboken). 2024 Nov 14. doi: 10.1002/acr.25465. Online ahead of print.

Abstract

Objective: This work aimed to evaluate the pharmacokinetics, efficacy, and safety of upadacitinib, an oral selective JAK inhibitor, in pediatric patients with polyarticular-course juvenile idiopathic arthritis (pcJIA).

Methods: In an open-label, phase 1 study (SELECT-YOUTH), enrolled patients, aged 2 to <18 years with pcJIA, received body weight-based upadacitinib doses using a twice-daily oral solution or once-daily extended-release tablet based on their body weight and ability to swallow tablets. The study included a 7-day pharmacokinetic assessment, followed by a long-term efficacy and safety evaluation for up to 156 weeks, including an additional long-term safety cohort. This interim analysis included available pharmacokinetic and safety data and efficacy data collected through week 48.

Results: A total of 57 patients received upadacitinib. The median time to maximum upadacitinib concentration was approximately three hours and one hour for the tablet and oral solution regimens, respectively; the harmonic mean functional half-life was approximately five hours and two hours, respectively. Juvenile idiopathic arthritis American College of Rheumatology 30, 50, 70, 90, and 100 responses at week 12 were 91.8%, 89.8%, 69.4%, 49.0%, and 32.7%, respectively. Efficacy was generally maintained through week 48, and improvement in additional efficacy end points was also observed. At a median exposure duration of 412 days, 52 of 57 patients reported adverse events; of these, 6 experienced serious adverse events. Adverse events were predominately mild to moderate in severity and consistent with the known safety profile of upadacitinib.

Conclusion: This interim analysis demonstrates that the bodyweight-based dosing regimen of upadacitinib was well tolerated and efficacious in pediatric patients with pcJIA.

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