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.

objectiveThis 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).

methodsIn 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.

resultsA 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.

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