Brunner Hermine I, Shmagel Anna, Horneff Gerd, Foeldvari Ivan, Antón Jordi, Ramanan Athimalaipet V, Qian Yuli, Unnebrink Kristina, Hao Shuai, Camp Heidi S, Khan Nasser, Liu Wei, Mohamed Mohamed-Eslam F
University of Cincinnati, Cincinnati Children's Hospital Medical Center, Ohio.
AbbVie Inc., North Chicago, Illinois.
Arthritis Care Res (Hoboken). 2025 May;77(5):584-593. doi: 10.1002/acr.25465. Epub 2024 Dec 22.
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).
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.
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.
This interim analysis demonstrates that the bodyweight-based dosing regimen of upadacitinib was well tolerated and efficacious in pediatric patients with pcJIA.
本研究旨在评估口服选择性JAK抑制剂乌帕替尼在多关节型幼年特发性关节炎（pcJIA）患儿中的药代动力学、疗效和安全性。
在一项开放标签的1期研究（SELECT-YOUTH）中，纳入年龄为2至<18岁的pcJIA患者，根据体重和吞咽片剂的能力，使用每日两次的口服溶液或每日一次的缓释片剂给予基于体重的乌帕替尼剂量。该研究包括为期7天的药代动力学评估，随后进行长达156周的长期疗效和安全性评估，包括一个额外的长期安全性队列。本次中期分析纳入了截至第48周收集的可用药代动力学、安全性数据和疗效数据。
共有57例患者接受了乌帕替尼治疗。乌帕替尼达到最大浓度的中位时间，片剂和口服溶液方案分别约为3小时和1小时；调和平均功能半衰期分别约为5小时和2小时。在第12周时，美国风湿病学会（ACR）制定的幼年特发性关节炎病情改善30%、50%、70%、90%和100%的应答率分别为91.8%、89.8%、69.4%、49.0%和32.7%。疗效一般维持到第48周，并且在其他疗效终点方面也观察到了改善。在中位暴露持续时间为412天时，57例患者中有52例报告了不良事件；其中6例发生了严重不良事件。不良事件的严重程度主要为轻至中度，与乌帕替尼已知的安全性特征一致。
本次中期分析表明，基于体重的乌帕替尼给药方案在pcJIA患儿中耐受性良好且有效。
