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.
Pedersen
Susanne Juhl
SJ
Department of Rheumatology, Copenhagen University Hospital, Herlev and Gentofte, Denmark. susanne_juhl_ped@dadlnet.dk
Hetland
Merete Lund
ML
Sørensen
Inge Juul
IJ
Ostergaard
Mikkel
M
Nielsen
Hans Jørgen
HJ
Johansen
Julia Sidenius
JS
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
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