PII-118 - EXTRAPOLATION APPROACH FOR UPADACITINIB IN JUVENILE IDIOPATHIC ARTHRITIS LEVERAGING PHARMACOKINETICS, EXPOSURE-RESPONSE, AND REAL-WORLD PATIENT DATA.

Y. Qian¹, L. Schlachter², D. Eckert², S. Stodtmann², A. Shmagel¹, Y. Peng¹, W. Liu³, M. Mohamed¹; ¹AbbVie Inc., ²AbbVie Deutschland GmbH & Co. KG, ³AbbVie Inc.

Background: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood with unmet medical needs. Upadacitinib is a Janus Kinase inhibitor that has been approved for treatment of various immune mediated diseases including rheumatoid arthritis (RA) and psoriatic arthritis (PsA), the adult forms of two JIA subtypes: polyarticular course JIA (pcJIA) and juvenile PsA (JPsA), respectively. This work aimed to characterize upadacitinib pharmacokinetics in pediatric patients and apply a modeling and simulation approach to extrapolate efficacy from adult RA and PsA to pcJIA and JPsA, respectively.

Methods: Two Phase 1 studies in pediatric patients with pcJIA (2 to < 18 years; N=51) and atopic dermatitis (2 to < 12 years; N=33) were conducted, where patients received upadacitinib using either immediate-release twice-daily (BID) oral solution or extended-release once-daily (QD) tablets based on their body weight and ability to swallow tablets. A population pharmacokinetic model was developed to describe the observed data from both studies while leveraging prior analyses in adults. Pharmacokinetic simulations were then conducted to compare upadacitinib plasma exposures in pediatric patients relative to the target exposures in adult patients. Efficacy simulations were conducted using previously developed exposure-response models in the adult indications and using pcJIA and JPsA patients’ information extracted from real-world databases (PremiOM JIA Data and Market Clarity Data, respectively).

Results: Pharmacokinetics of upadacitinib in pediatric patients were adequately described by the population pharmacokinetic model. Model-predicted median upadacitinib plasma exposures following the administration of the proposed weight-based dosing regimen (Table 1) in pediatric patients were within 20% of those in adult RA and PsA patients receiving the approved 15 mg QD regimen. Simulations for key efficacy endpoints demonstrated that upadacitinib efficacy in pcJIA and JPsA is predicted to be non-inferior to efficacy in adults with RA and PsA, respectively.

Conclusion: The proposed pediatric regimen is predicted to achieve comparable upadacitinib plasma exposures and efficacy to those achieved in adults with the approved 15 mg QD dose. Further assessments are warranted to inform upadacitinib benefit-risk profile in JIA.