Population pharmacokinetics and exposure‐response analyses for efficacy and safety of upadacitinib in patients with axial spondyloarthritis

Abstract

Abstract Upadacitinib is an orally administered, selective, Janus kinase inhibitor that is approved for several auto‐immune conditions, such as axial spondyloarthritis, an inflammatory rheumatic disease that includes ankylosing spondylitis (AS) and non‐radiographic axial spondyloarthritis (nr‐axSpA). The approvals of upadacitinib for the treatment of AS and nr‐axSpA were based on the safety and efficacy data for upadacitinib 15 mg once‐daily compared to placebo from the SELECT‐AXIS 1 and SELECT‐AXIS 2 studies. Population pharmacokinetic analyses based on data from 244 patients with axSpA showed that the pharmacokinetics of upadacitinib were comparable in subjects with AS and nr‐axSpA. Exposure‐response relationships were characterized for key efficacy and safety end points using data from 482 patients with axSpA. The exposure‐response analyses for efficacy based on Assessment of SpondyloArthritis International Society (ASAS)20 and ASAS40 responses at week 14, showed a clear differentiation from placebo with no evidence of increased responses with increasing upadacitinib plasma exposures. There were no clear exposure‐response trends observed for safety end points that included serious infections, herpes zoster, pneumonia, lymphopenia (grade ≥3), neutropenia (grade ≥3), or a greater than 2 g/dL decrease in hemoglobin from baseline through week 14. The exposure‐response analyses for efficacy and safety presented here supported the favorable benefit–risk profile with the use of upadacitinib 15 mg once‐daily for the treatment of axSpA.