Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNFα inhibitors

The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated with tumor necrosis factor-alpha (TNFα) inhibitors and to compare with levels in healthy subjects. Biomarkers were measured in an observational cohort of 49 SpA patients (ankylosing spondylitis, n = 32, and psoriatic arthritis, n = 17) initiating TNFα inhibitor therapy (infliximab, n = 38; etanercept, n = 8; and adalimumab, n = 3) and compared with levels in healthy subjects. Clinical parameters and biomarkers were measured at baseline, weeks 2, 6, and every 6–12 weeks for up to 3 years. Patients with co-morbidities (n = 4), missing baseline samples (n = 3), and adverse events (n = 5) were excluded. Patients with SpA had compared with healthy subjects elevated IL-6 (median 8.5 ng/l (range, 0.98–64) vs. 1.3 (0.33–26)), VEGF (105 ng/l (22–752) vs. 45 (12–351)), YKL-40 (74 μg/l (14–572) vs. 43 (20–184)), and MMP-3 (43 μg/l (9.1–401) vs. 16 (2.5–47), p ≤ 0.001), whereas total aggrecan was lower (662 μg/l (223–2,219) vs. 816 (399–2,190),p ≤ 0.001). Two weeks after first treatment, all biomarker levels changed towards normal levels (p ≤ 0.03) in clinical responders (n = 24), and persistent reductions over 3 years were found in IL-6, VEGF, YKL-40, and MMP-3. Only MMP-3 decreased (p ≤ 0.02) in non-responders (n = 13). The study demonstrated changes of plasma IL-6, VEGF, YKL-40, MMP-3, and total aggrecan and a potential value for monitoring disease activity and treatment response in SpA patients. Larger prospective studies are required to clarify clinical utility of these biomarkers.