ASDAS, BASDAI and different treatment responses and their relation to biomarkers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNFα inhibitors

Susanne Juhl Pedersen; Inge Juul Sørensen; Patrick Garnero; Julia Sidenius Johansen; Ole Rintek Madsen; Niels Tvede; Michael Sejer Hansen; Gorm Thamsborg; Lis Smedegaard Andersen; Ole Majgaard; Anne Gitte Loft; Jon Erlendsson; Karsten Asmussen; Anne Grethe Jurik; Jakob Møller; Maria Hasselquist; Dorrit Mikkelsen; Thomas Skjødt; Robert Lambert; Annette Hansen; Mikkel Østergaard

doi:10.1136/ard.2010.138883

ASDAS, BASDAI and different treatment responses and their relation to biomarkers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNFα inhibitors

Susanne Juhl Pedersen, Inge Juul Sørensen, Patrick Garnero, Julia Sidenius Johansen, Ole Rintek Madsen, Niels Tvede, Michael Sejer Hansen, Gorm Thamsborg, Lis Smedegaard Andersen, Ole Majgaard, Anne Gitte Loft, Jon Erlendsson, Karsten Asmussen, Anne Grethe Jurik, Jakob Møller, Maria Hasselquist, Dorrit Mikkelsen, Thomas Skjødt, Robert Lambert, Annette HansenMikkel Østergaard

86 Citations (Scopus)

Abstract

Objectives: To investigate the relation between ankylosing spondylitis disease activity score (ASDAS), Bath ankylosing spondylitis disease activity index (BASDAI) and treatment response and biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), YKL-40), angiogenesis (vascular endothelial growth factor (VEGF)), cartilage (C-terminal crosslinking telopeptide of type II collagen (CTX-II), matrix metalloproteinase-3 (MMP-3), total aggrecan, cartilage oligomeric matrix protein) and bone (C-terminal crosslinking telopeptide of type I collagen, osteocalcin) turnover in 60 patients with axial spondyloarthritis initiating tumour necrosis factor alpha (TNFα) inhibitor therapy. Methods: ASDAS (CRP-based), BASDAI and biomarkers were determined before and seven times during 46 weeks of TNFα inhibitor therapy. Results: Very high ASDAS were associated with high levels of inflammatory biomarkers, while high BASDAI were not related to any biomarkers. Mixed modeling demonstrated significant longitudinal associations between ASDAS and IL-6, VEGF, MMP-3 and osteocalcin and between BASDAI and CRP, IL-6 and VEGF. Major improvement in ASDAS was associated with larger percentage decreases in biomarkers of inflammation, angiogenesis, MMP-3 and increases in aggrecan and osteocalcin. BASDAI response was associated with larger decreases in CRP and IL-6. Biomarkers with moderate/ high differences in responsiveness for major versus no/ clinically important improvement in ASDAS were CRP, IL-6, VEGF, aggrecan and osteocalcin, and VEGF and CTX-II for BASDAI response versus non-response. Conclusion: Levels and changes of 10 biomarkers in patients with axial spondyloarthritis during anti-TNFα therapy were documented. Construct validity and responsiveness of IL-6, VEGF, MMP-3, total aggrecan and osteocalcin were demonstrated. ASDAS was more associated with these biomarkers than BASDAI, and may better reflect the inflammatory disease processes. ClinicalTrials.gov identifier NCT00133315.

Original language	English
Journal	Annals of the Rheumatic Diseases
Volume	70
Issue number	8
Pages (from-to)	1375-81
Number of pages	7
ISSN	0003-4967
DOIs	https://doi.org/10.1136/ard.2010.138883
Publication status	Published - Aug 2011

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Pedersen, S. J., Sørensen, I. J., Garnero, P., Johansen, J. S., Madsen, O. R., Tvede, N., Hansen, M. S., Thamsborg, G., Andersen, L. S., Majgaard, O., Loft, A. G., Erlendsson, J., Asmussen, K., Jurik, A. G., Møller, J., Hasselquist, M., Mikkelsen, D., Skjødt, T., Lambert, R., ... Østergaard, M. (2011). ASDAS, BASDAI and different treatment responses and their relation to biomarkers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNFα inhibitors. Annals of the Rheumatic Diseases, 70(8), 1375-81. https://doi.org/10.1136/ard.2010.138883

ASDAS, BASDAI and different treatment responses and their relation to biomarkers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNFα inhibitors. / Pedersen, Susanne Juhl; Sørensen, Inge Juul; Garnero, Patrick et al.

In: Annals of the Rheumatic Diseases, Vol. 70, No. 8, 08.2011, p. 1375-81.

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

Pedersen, SJ, Sørensen, IJ, Garnero, P, Johansen, JS , Madsen, OR, Tvede, N, Hansen, MS, Thamsborg, G, Andersen, LS, Majgaard, O, Loft, AG, Erlendsson, J, Asmussen, K, Jurik, AG, Møller, J, Hasselquist, M, Mikkelsen, D, Skjødt, T, Lambert, R, Hansen, A & Østergaard, M 2011, 'ASDAS, BASDAI and different treatment responses and their relation to biomarkers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNFα inhibitors', Annals of the Rheumatic Diseases, vol. 70, no. 8, pp. 1375-81. https://doi.org/10.1136/ard.2010.138883

@article{fc14d7ec1cb7434db91ffe0146bc815d,

title = "ASDAS, BASDAI and different treatment responses and their relation to biomarkers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNFα inhibitors",

abstract = "Objectives: To investigate the relation between ankylosing spondylitis disease activity score (ASDAS), Bath ankylosing spondylitis disease activity index (BASDAI) and treatment response and biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), YKL-40), angiogenesis (vascular endothelial growth factor (VEGF)), cartilage (C-terminal crosslinking telopeptide of type II collagen (CTX-II), matrix metalloproteinase-3 (MMP-3), total aggrecan, cartilage oligomeric matrix protein) and bone (C-terminal crosslinking telopeptide of type I collagen, osteocalcin) turnover in 60 patients with axial spondyloarthritis initiating tumour necrosis factor alpha (TNFα) inhibitor therapy. Methods: ASDAS (CRP-based), BASDAI and biomarkers were determined before and seven times during 46 weeks of TNFα inhibitor therapy. Results: Very high ASDAS were associated with high levels of inflammatory biomarkers, while high BASDAI were not related to any biomarkers. Mixed modeling demonstrated significant longitudinal associations between ASDAS and IL-6, VEGF, MMP-3 and osteocalcin and between BASDAI and CRP, IL-6 and VEGF. Major improvement in ASDAS was associated with larger percentage decreases in biomarkers of inflammation, angiogenesis, MMP-3 and increases in aggrecan and osteocalcin. BASDAI response was associated with larger decreases in CRP and IL-6. Biomarkers with moderate/ high differences in responsiveness for major versus no/ clinically important improvement in ASDAS were CRP, IL-6, VEGF, aggrecan and osteocalcin, and VEGF and CTX-II for BASDAI response versus non-response. Conclusion: Levels and changes of 10 biomarkers in patients with axial spondyloarthritis during anti-TNFα therapy were documented. Construct validity and responsiveness of IL-6, VEGF, MMP-3, total aggrecan and osteocalcin were demonstrated. ASDAS was more associated with these biomarkers than BASDAI, and may better reflect the inflammatory disease processes. ClinicalTrials.gov identifier NCT00133315.",

author = "Pedersen, {Susanne Juhl} and S{\o}rensen, {Inge Juul} and Patrick Garnero and Johansen, {Julia Sidenius} and Madsen, {Ole Rintek} and Niels Tvede and Hansen, {Michael Sejer} and Gorm Thamsborg and Andersen, {Lis Smedegaard} and Ole Majgaard and Loft, {Anne Gitte} and Jon Erlendsson and Karsten Asmussen and Jurik, {Anne Grethe} and Jakob M{\o}ller and Maria Hasselquist and Dorrit Mikkelsen and Thomas Skj{\o}dt and Robert Lambert and Annette Hansen and Mikkel {\O}stergaard",

year = "2011",

month = aug,

doi = "10.1136/ard.2010.138883",

language = "English",

volume = "70",

pages = "1375--81",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "B M J Group",

number = "8",

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TY - JOUR

T1 - ASDAS, BASDAI and different treatment responses and their relation to biomarkers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNFα inhibitors

AU - Pedersen, Susanne Juhl

AU - Sørensen, Inge Juul

AU - Garnero, Patrick

AU - Johansen, Julia Sidenius

AU - Madsen, Ole Rintek

AU - Tvede, Niels

AU - Hansen, Michael Sejer

AU - Thamsborg, Gorm

AU - Andersen, Lis Smedegaard

AU - Majgaard, Ole

AU - Loft, Anne Gitte

AU - Erlendsson, Jon

AU - Asmussen, Karsten

AU - Jurik, Anne Grethe

AU - Møller, Jakob

AU - Hasselquist, Maria

AU - Mikkelsen, Dorrit

AU - Skjødt, Thomas

AU - Lambert, Robert

AU - Hansen, Annette

AU - Østergaard, Mikkel

PY - 2011/8

Y1 - 2011/8

N2 - Objectives: To investigate the relation between ankylosing spondylitis disease activity score (ASDAS), Bath ankylosing spondylitis disease activity index (BASDAI) and treatment response and biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), YKL-40), angiogenesis (vascular endothelial growth factor (VEGF)), cartilage (C-terminal crosslinking telopeptide of type II collagen (CTX-II), matrix metalloproteinase-3 (MMP-3), total aggrecan, cartilage oligomeric matrix protein) and bone (C-terminal crosslinking telopeptide of type I collagen, osteocalcin) turnover in 60 patients with axial spondyloarthritis initiating tumour necrosis factor alpha (TNFα) inhibitor therapy. Methods: ASDAS (CRP-based), BASDAI and biomarkers were determined before and seven times during 46 weeks of TNFα inhibitor therapy. Results: Very high ASDAS were associated with high levels of inflammatory biomarkers, while high BASDAI were not related to any biomarkers. Mixed modeling demonstrated significant longitudinal associations between ASDAS and IL-6, VEGF, MMP-3 and osteocalcin and between BASDAI and CRP, IL-6 and VEGF. Major improvement in ASDAS was associated with larger percentage decreases in biomarkers of inflammation, angiogenesis, MMP-3 and increases in aggrecan and osteocalcin. BASDAI response was associated with larger decreases in CRP and IL-6. Biomarkers with moderate/ high differences in responsiveness for major versus no/ clinically important improvement in ASDAS were CRP, IL-6, VEGF, aggrecan and osteocalcin, and VEGF and CTX-II for BASDAI response versus non-response. Conclusion: Levels and changes of 10 biomarkers in patients with axial spondyloarthritis during anti-TNFα therapy were documented. Construct validity and responsiveness of IL-6, VEGF, MMP-3, total aggrecan and osteocalcin were demonstrated. ASDAS was more associated with these biomarkers than BASDAI, and may better reflect the inflammatory disease processes. ClinicalTrials.gov identifier NCT00133315.

AB - Objectives: To investigate the relation between ankylosing spondylitis disease activity score (ASDAS), Bath ankylosing spondylitis disease activity index (BASDAI) and treatment response and biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), YKL-40), angiogenesis (vascular endothelial growth factor (VEGF)), cartilage (C-terminal crosslinking telopeptide of type II collagen (CTX-II), matrix metalloproteinase-3 (MMP-3), total aggrecan, cartilage oligomeric matrix protein) and bone (C-terminal crosslinking telopeptide of type I collagen, osteocalcin) turnover in 60 patients with axial spondyloarthritis initiating tumour necrosis factor alpha (TNFα) inhibitor therapy. Methods: ASDAS (CRP-based), BASDAI and biomarkers were determined before and seven times during 46 weeks of TNFα inhibitor therapy. Results: Very high ASDAS were associated with high levels of inflammatory biomarkers, while high BASDAI were not related to any biomarkers. Mixed modeling demonstrated significant longitudinal associations between ASDAS and IL-6, VEGF, MMP-3 and osteocalcin and between BASDAI and CRP, IL-6 and VEGF. Major improvement in ASDAS was associated with larger percentage decreases in biomarkers of inflammation, angiogenesis, MMP-3 and increases in aggrecan and osteocalcin. BASDAI response was associated with larger decreases in CRP and IL-6. Biomarkers with moderate/ high differences in responsiveness for major versus no/ clinically important improvement in ASDAS were CRP, IL-6, VEGF, aggrecan and osteocalcin, and VEGF and CTX-II for BASDAI response versus non-response. Conclusion: Levels and changes of 10 biomarkers in patients with axial spondyloarthritis during anti-TNFα therapy were documented. Construct validity and responsiveness of IL-6, VEGF, MMP-3, total aggrecan and osteocalcin were demonstrated. ASDAS was more associated with these biomarkers than BASDAI, and may better reflect the inflammatory disease processes. ClinicalTrials.gov identifier NCT00133315.

U2 - 10.1136/ard.2010.138883

DO - 10.1136/ard.2010.138883

M3 - Journal article

SN - 0003-4967

VL - 70

SP - 1375

EP - 1381

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 8

ER -

ASDAS, BASDAI and different treatment responses and their relation to biomarkers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNFα inhibitors

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