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

Susanne Juhl Pedersen; Merete Lund Hetland; Inge Juul Sørensen; Mikkel Ostergaard; Hans Jørgen Nielsen; Julia Sidenius Johansen; Susanne Juhl Pedersen; Merete Lund Hetland; Mikkel Østergaard; Julia Sidenius Johansen

doi:10.1007/s10067-010-1528-x

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

Susanne Juhl Pedersen, Merete Lund Hetland, Inge Juul Sørensen, Mikkel Ostergaard, Hans Jørgen Nielsen, Julia Sidenius Johansen, Susanne Juhl Pedersen, Merete Lund Hetland, Mikkel Østergaard, Julia Sidenius Johansen

56 Citations (Scopus)

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.

Original language	English
Journal	Clinical Rheumatology
Volume	29
Issue number	11
Pages (from-to)	1301-9
Number of pages	9
ISSN	0770-3198
DOIs	https://doi.org/10.1007/s10067-010-1528-x
Publication status	Published - Nov 2010

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Pedersen, S. J., Hetland, M. L., Sørensen, I. J., Ostergaard, M., Nielsen, H. J., Johansen, J. S., Pedersen, S. J., Hetland, M. L., Østergaard, M., & Johansen, J. S. (2010). 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. Clinical Rheumatology, 29(11), 1301-9. https://doi.org/10.1007/s10067-010-1528-x

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. / Pedersen, Susanne Juhl; Hetland, Merete Lund; Sørensen, Inge Juul et al.

In: Clinical Rheumatology, Vol. 29, No. 11, 11.2010, p. 1301-9.

Research output: Contribution to journal › Journal article › Research › peer-review

Pedersen, SJ, Hetland, ML, Sørensen, IJ, Ostergaard, M, Nielsen, HJ, Johansen, JS, Pedersen, SJ, Hetland, ML , Østergaard, M & Johansen, JS 2010, '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', Clinical Rheumatology, vol. 29, no. 11, pp. 1301-9. https://doi.org/10.1007/s10067-010-1528-x

Pedersen SJ, Hetland ML, Sørensen IJ, Ostergaard M, Nielsen HJ, Johansen JS et al. 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. Clinical Rheumatology. 2010 Nov;29(11):1301-9. doi: 10.1007/s10067-010-1528-x

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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.",

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T1 - 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

AU - Pedersen, Susanne Juhl

AU - Hetland, Merete Lund

AU - Sørensen, Inge Juul

AU - Ostergaard, Mikkel

AU - Nielsen, Hans Jørgen

AU - Johansen, Julia Sidenius

AU - Pedersen, Susanne Juhl

AU - Hetland, Merete Lund

AU - Østergaard, Mikkel

AU - Johansen, Julia Sidenius

PY - 2010/11

Y1 - 2010/11

N2 - 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.

AB - 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.

U2 - 10.1007/s10067-010-1528-x

DO - 10.1007/s10067-010-1528-x

M3 - Journal article

SN - 0770-3198

VL - 29

SP - 1301

EP - 1309

JO - Clinical Rheumatology

JF - Clinical Rheumatology

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ER -