Collagen Turnover Biomarkers Associate with Active Psoriatic Arthritis and Decrease with Guselkumab Treatment in a Phase 3 Clinical Trial (DISCOVER-2)

INTRODUCTION: Guselkumab, a novel interleukin-23p19 subunit monoclonal antibody, has been shown to effectively improve the diverse manifestations of active psoriatic arthritis (PsA) in two phase 3 trials (DISCOVER-1, DISCOVER-2). Serum concentrations of extracellular matrix (ECM) biomarkers at baseline and following treatment with guselkumab were evaluated in patients with active PsA, and the relationship of these biomarkers with baseline PsA characteristics and clinical response to guselkumab treatment was explored. METHODS: Serum samples were collected at weeks 0, 4, 24, and 52 from a selected subset (N = 260) of the 739 biologic-naïve patients with PsA treated with guselkumab 100 mg every 4 or 8 weeks or placebo in DISCOVER-2. Demographically matched healthy controls (N = 76) were used for comparison. The samples were analyzed for ECM biomarkers associated with collagen degradation (C1M, C2M, C3M, C4M, C6M, C10C) and collagen formation (PRO-C1, PRO-C2, PRO-C3, PRO-C4, PRO-C6). RESULTS: Baseline concentrations of collagen degradation biomarkers C1M, C3M, C4M, and C6M and collagen formation biomarkers PRO-C3 and PRO-C6 were significantly higher (i.e., ≥ 1.25-fold and false discovery rate adjusted p < 0.05) in PsA patients than in healthy controls. Serum C1M, C3M, C4M, and C6M levels declined from baseline in guselkumab-treated patients in both dosing regimens. In addition, guselkumab-treated ACR20 responders (≥ 20% improvement in American College of Rhematology response criteria) had significantly lower C1M levels than ACR20 nonresponders. CONCLUSION: These data demonstrate that serum collagen biomarkers are elevated in patients with PsA compared with healthy controls and that treatment with guselkumab decreases levels of C1M, C3M, C4M, and C6M. Importantly, C1M serves as a biomarker that associates with improvement of joint signs and symptoms. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03158285. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40744-022-00444-x.