Abstract

Objectives 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 bodyweight‐based upadacitinib doses using a twice‐daily (BID) oral solution or once‐daily (QD) 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 3 hours and 1 hour for the tablet and oral solution regimens, respectively; the harmonic mean functional half‐life was approximately 5 hours and 2 hours, respectively. Juvenile idiopathic arthritis (JIA) American College of Rheumatology (ACR)30/50/70/90/100 responses at Week 12 were 91.8/89.8/69.4/49.0/32.7%, respectively. Efficacy was generally maintained through Week 48, and improvement in additional efficacy endpoints 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. Conclusions This interim analysis demonstrates that the bodyweight‐based dosing regimen of upadacitinib was well tolerated and efficacious in pediatric patients with pcJIA.