Effectiveness of interleukin (IL)-23 and IL-12/23 inhibitors and factors associated with response in psoriatic arthritis with axial involvement: the APxis-IL12-23 study

Abstract

OBJECTIVES: To assess the real-world effectiveness of two interleukin (IL)-23 inhibitors [guselkumab (GUS), risankizumab (RIS)] and an IL-12/23 inhibitor [ustekinumab (UST)] in patients with purely axial psoriatic arthritis (PsA) or mixed PsA (both axial and peripheral involvement), and identify response predictors. METHOD: In this retrospective multicentre study of patients treated with GUS, RIS, or UST, composite treatment response was defined as achieving a clinically important improvement (≥1.1) in Axial Spondyloarthritis Disease Activity Score-C-reactive protein (ASDAS-CRP) or ≥50% improvement from the initial Bath Ankylosing Spondylitis Disease Activity Index value (BASDAI50). Disease activity was evaluated using mixed models, and predictors were evaluated by modified Poisson regression. RESULTS: In total, 167 patients were included: 87.4% had mixed PsA and 12.6% purely axial PsA. Baseline therapies were GUS (47.9%), RIS (13.2%), and UST (38.9%). Significant decreases in ASDAS-CRP and BASDAI (p < 0.001) occurred over 12 months. The total cohort's composite response rate at 12 months was 26.4%. Notably, 12 month response rates were numerically higher for IL-23 inhibitors (GUS 30.4%, RIS 40.0%) than for UST (15.7%), although these differences lacked statistical significance. Fulfilling Assessment of Spondyloarthritis International Society (ASAS) criteria [relative risk (RR) = 7.25, p = 0.023] and baseline ASDAS-CRP > 2.1 (RR = 2.30, p < 0.001) independently predicted clinical response. CONCLUSION: IL-23 and IL-12/23 inhibitors improved disease activity in a predominantly mixed PsA cohort. Although IL-23 inhibitors exhibited higher numerical response rates, statistical superiority over UST was not confirmed. Effectiveness strongly correlated with baseline disease burden and ASAS criteria.