title: 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.
abstract: 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.
authors.affiliation: Department of Rheumatology, Copenhagen University Hospital, Herlev and Gentofte, Denmark. susanne_juhl_ped@dadlnet.dk
authors.forename: Susanne Juhl
authors.initials: SJ
authors.lastname: Pedersen
authors.forename: Merete Lund
authors.initials: ML
authors.lastname: Hetland
authors.forename: Inge Juul
authors.initials: IJ
authors.lastname: Sørensen
authors.forename: Mikkel
authors.initials: M
authors.lastname: Ostergaard
authors.forename: Hans Jørgen
authors.initials: HJ
authors.lastname: Nielsen
authors.forename: Julia Sidenius
authors.initials: JS
authors.lastname: Johansen
mesh_terms: D054392:Adipokines; D000328:Adult; D000368:Aged; D053674:Aggrecans / Q000096:biosynthesis*; D015415:Biomarkers / Q000378:metabolism; D000071451:Chitinase-3-Like Protein 1; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood* / Q000378:metabolism; D037102:Lectins / Q000097:blood*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D008875:Middle Aged; D025241:Spondylarthritis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood* / Q000378:metabolism
chemical_list: D054392:Adipokines; D053674:Aggrecans; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D015850:Interleukin-6; D037102:Lectins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D019278:Matrix Metalloproteinase 3