Approval of Upadacitinib in Pediatric Patients with Active Polyarticular Juvenile Idiopathic Arthritis or Active Psoriatic Arthritis: A Regulatory Perspective

On April 26, 2024, FDA approved Rinvoq (upadacitinib, extended-release [ER] tablets) and Rinvoq LQ (1 mg/mL oral solution), a new pediatric immediate-release (IR) formulation, for the treatment of active polyarticular juvenile idiopathic arthritis (pJIA) and active psoriatic arthritis (PsA) in patients 2 years of age and older. The approved dosing regimens include a weight-tiered twice daily (BID) regimen with IR oral solution and a once-daily (QD) regimen with ER tablets. The objective of this article is to summarize the FDA's major review findings and considerations supporting these approvals from a regulatory perspective. This clinical development program included a single study (Study 1) conducted in pediatric subjects aged 2 to less than 18 years with JIA with active polyarthritis to evaluate the pharmacokinetics (PK), safety, and tolerability of multiple doses of upadacitinib. No clinical trials or dedicated PK studies were conducted in pediatric patients with PsA. Efficacy was extrapolated from adults with rheumatoid arthritis (RA) or PsA to pediatric patients with pJIA or PsA, respectively, based on a PK-matching approach considering disease similarity, similar response to treatment, and comparable PK exposure. PK data analysis and simulations showed that the approved upadacitinib pediatric dosing regimen, including a BID regimen with IR oral solution and QD regimen with ER tablet, provide comparable PK exposure (Cmax and AUC) in pediatric subjects with pJIA or PsA as compared to the approved 15 mg ER tablet QD regimen in adults with RA or PsA, respectively, supporting the efficacy extrapolation from adults to pediatric subjects.