OP0016 EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH ACTIVE NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED PHASE 3 TRIAL

Abstract

BackgroundJanus kinase (JAK) inhibitors have been recognized as a potential therapeutic option in ankylosing spondylitis (AS), also known as radiographic axial spondyloarthritis (r-axSpA).1 Upadacitinib (UPA), a JAK inhibitor, has demonstrated efficacy and safety in the treatment of AS2; however, no JAK inhibitor studies have been conducted in non-radiographic axSpA (nr-axSpA) to date.ObjectivesTo assess the efficacy and safety of UPA in patients (pts) with active nr-axSpA.MethodsSELECT-AXIS 2 (NCT04169373) was conducted under a master protocol comprising two independent studies, one in an AS population with an inadequate response to biologic disease-modifying antirheumatic drugs and one in an nr-axSpA population. The nr-axSpA study is a randomized, double-blind, placebo(PBO)-controlled, phase 3 trial that enrolled adults ≥18 years with a clinical diagnosis of nr-axSpA (who also fulfilled 2009 ASAS classification criteria for axSpA but did not meet the radiologic criterion of modified New York criteria), who had objective signs of active inflammation consistent with axSpA on MRI of the sacroiliac (SI) joints and/or high sensitivity C-reactive protein (hs-CRP) >upper limit of normal (2.87 mg/L) at screening, and who had BASDAI and pt’s assessment of total back pain scores ≥4 based on a 0 to 10 numeric rating scale at study entry. Pts were randomized 1:1 to receive oral UPA 15 mg once daily (QD) or PBO during a 52-week (wk) double-blind treatment period. The primary endpoint was ASAS40 response at wk 14. Multiplicity-controlled secondary endpoints assessed at wk 14 included BASDAI50, ASDAS ID (<1.3), ASDAS LDA (<2.1), ASDAS PR, and ASAS20, and the change from baseline (Δ) in ASDAS (CRP), SPARCC MRI SI joint inflammation score, total and nocturnal back pain, BASFI, ASQoL, ASAS HI, BASMI, and MASES. Treatment-emergent adverse events (TEAEs) are reported through wk 14 for pts who received ≥1 dose of study drug.ResultsOf 314 pts randomized at baseline, 313 received study drug (UPA 15 mg, n=156; PBO, n=157) and 295 (94%) received study drug through wk 14. Baseline demographic and disease characteristics were balanced across treatment groups and consistent with an active nr-axSpA population (58% female; mean age 42.1 years; mean BASDAI 6.9; mean hs-CRP 12.1 mg/L). A significantly higher ASAS40 response rate at wk 14 was achieved with UPA vs PBO (45% vs 23%; P<0.0001; Figure 1). Statistical significance was also achieved in the first 12 of the 14 multiplicity-controlled secondary endpoints (ie, all endpoints except BASMI and MASES) at wk 14 for UPA compared with PBO (P<0.01; Figure 1). The proportion of pts who experienced a TEAE was similar between treatment groups (UPA, 48%; PBO, 46%). Serious TEAEs and TEAEs leading to discontinuation were reported in 4 (2.6%) pts treated with UPA and 2 (1.3%) pts treated with PBO, respectively. Few pts had serious infection or herpes zoster (each 2 [1.3%] pts on UPA; each 1 [0.6%] pt on PBO, respectively). Uveitis was reported in 1 (0.6%) pt on UPA who had a history of uveitis and none on PBO. No malignancy other than non-melanoma skin cancer, major adverse cardiovascular events, venous thromboembolic events, inflammatory bowel disease (IBD), or death were reported in the study; 1 event of basal cell carcinoma occurred with PBO.ConclusionUPA 15 mg QD demonstrated significantly greater improvements in disease activity, pain, function, quality of life, and MRI-detected SI joint inflammation than PBO after 14 wks of treatment in pts with active nr-axSpA. The safety profile of UPA was consistent with what has been observed with other inflammatory musculoskeletal diseases,3–5 and no new risks were identified. These results support the potential use of UPA in pts with active nr-axSpA.