Discussion
PsA, hepatic disorder, axial disease, reduced disease, inflammation, axSpA, sacroiliitis, pain, sacroiliac joints
NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS, HEPATIC DISORDER, INFLAMMATION, DISEASE, NR-AXSPA, SACROILIITIS
Here, we demonstrate that based on two different definitions of axial involvement, patients with active PsA and axial involvement had greater clinical responses for measures related to their axial symptoms (as determined by BASDAI and ASDAS) with upadacitinib 15 mg (approved dose) versus placebo at week 12, which were maintained or further improved at week 24 in both SELECT-PsA 1 (non-bDMARD-IR population) and SELECT-PsA 2 (bDMARD-IR population). In addition, SELECT-PsA 1 patients often had similar or greater numerical responses compared to adalimumab across multiple endpoints related to axial disease activity. Clinical improvements observed with upadacitinib 15 mg were maintained long-term at week 56. Responses were consistent across patient populations (non-bDMARD-IR and bDMARD-IR), endpoints (BASDAI, individual BASDAI components including question 2 related to back pain, and ASDAS), and assessments for axial involvement (investigator alone or investigator and PRO-based criteria), demonstrating support for inhibition of the JAK-STAT signaling pathway to improve axial symptoms in patients with active PsA. Complementary to the efficacy of upadacitinib in PsA with axial involvement, upadacitinib 15 mg reduced disease activity and axial inflammation (as detected by magnetic resonance imaging [MRI]), as well as improved function, in patients with AS or non-radiographic axial spondyloarthritis (nr-axSpA), providing further support from dedicated AS and axSpA studies for the efficacy of JAK inhibitors to treat axial disease [PsA with axial involvement remains a topic of high clinical interest due to limited data on this specific patient population and no agreed upon classification or diagnostic criteria for axial involvement. Previous studies have utilized a variety of criteria to classify axial involvement in PsA, including applying CASPAR or Assessment of SpondyloArthritis international Society (ASAS) criteria, BASDAI cut-offs, presence of inflammatory back pain, sacroiliitis on imaging, and/or other criteria [In this post-hoc analysis of the SELECT-PsA trials, the safety profile of upadacitinib 15 mg was generally similar between patients with axial involvement using either criterion, as well as those without axial involvement. Minor variability in the rates of some TEAEs (eg, hepatic disorder in SELECT-PsA 1 [non-bDMARD-IR] or CPK elevation in SELECT-PsA 2 [bDMARD-IR]) were noted in patients with axial involvement, but no clear patterns were observed across the two studies. No new safety risks were identified with upadacitinib 15 mg treatment in this post-hoc analysis of the SELECT-PsA studies [Potential limitations of this post-hoc analysis should also be considered. First, axial involvement in the SELECT-PsA trials was determined by investigator judgement and was not consistently confirmed by imaging in all patients. Improvements in active MRI inflammation in the spine and sacroiliac joints has been demonstrated previously with upadacitinib treatment in patients with AS or nr-axSpA [