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Research ArticleArticle

Beneficial Effects of Adalimumab on Biomarkers Reflecting Structural Damage in Patients with Ankylosing Spondylitis

WALTER P. MAKSYMOWYCH, PROTON RAHMAN, KAM SHOJANIA, WOJCIECH P. OLSZYNSKI, GLEN T.D. THOMSON, SHAILA BALLAL, ROBERT L. WONG and ROBERT D. INMAN
The Journal of Rheumatology October 2008, 35 (10) 2030-2037;
WALTER P. MAKSYMOWYCH
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  • For correspondence: walter.maksymowych@ualberta.ca
PROTON RAHMAN
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KAM SHOJANIA
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WOJCIECH P. OLSZYNSKI
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GLEN T.D. THOMSON
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SHAILA BALLAL
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ROBERT L. WONG
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ROBERT D. INMAN
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Abstract

Objective

We analyzed the effects of adalimumab on biomarkers predictive of structural damage in inflammatory arthritis.

Methods

In a 24-week randomized controlled trial, patients with active ankylosing spondylitis (AS) received adalimumab 40 mg or placebo every other week. Efficacy measures included ASsessment in Ankylosing Spondylitis International Working Group response, Bath AS Disease Activity Index (BASDAI), Total Back Pain, Bath AS Functional Index, C-reactive protein (CRP), and patient’s global assessment of disease activity. Urinary type II collagen C-telopeptides (CTX-II), serum type I collagen N-telopeptides (NTX), and serum metalloproteinase-3 (MMP-3) were assessed using ELISA for treatment-group differences at baseline, 12, and 24 weeks. We determined correlations between changes in biomarkers and AS efficacy outcomes.

Results

A total of 82 patients (38 adalimumab, 44 placebo) enrolled. At 12 and 24 weeks, significant reductions in urinary CTX-II and MMP-3, but not NTX concentrations, were observed for adal-imumab versus placebo (p < 0.001). Significant baseline correlations were noted between CRP and CTX-II (r = 0.71), MMP-3 (r = 0.45), and NTX (r = 0.37) (p ≤ 0.001), as well as between CTX-II and NTX (r = 0.49; p < 0.0001). Changes in CTX-II and MMP-3 at 12 weeks correlated significantly with changes in BASDAI (r = 0.31 and 0.33), and CRP (r = 0.40 and 0.43) (p ≤0.005). Change in CTX-II at 12 weeks also correlated significantly with change in MMP-3 (r = 0.41; p < 0.0001).

Conclusion

Adalimumab suppresses biomarkers that reflect matrix turnover in patients with AS.

Key Indexing Terms:
  • ANKYLOSING SPONDYLITIS
  • ADALIMUMAB
  • RANDOMIZED CONTROLLED TRIAL
  • METALLOPROTEINASE 3
  • URINARY TYPE II COLLAGEN C-TELOPEPTIDE

Footnotes

  • W.P. Maksymowych, MB, CHB, FRCP(UK), FRCPC, FACP, Professor, Department of Medicine, University of Alberta; P. Rahman, MD, MSc, FRCPC, Associate Professor, Department of Medicine, Memorial University; K. Shojania, MD, Clinical Associate Professor, Department of Medicine, University of British Columbia; W.P. Olszynski, MD, PhD, Clinical Professor, University of Saskatchewan; G.T.D. Thomson, MD, FRCPC, Clinical Associate Professor, Centre for Inflammatory and Arthritis Disease Studies, University of Manitoba; S. Ballal, MS, Manager, Statistics; R.L. Wong, MD, Senior Medical Director, Abbott Laboratories; R.D. Inman, MD, BA, Professor, Department of Medicine, University of Toronto.

  • Supported by Abbott Laboratories. Prof. Maksymowych is a Scientist of the Alberta Heritage Foundation for Medical Research.

    • Accepted for publication May 21, 2008.
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The Journal of Rheumatology
Vol. 35, Issue 10
1 Oct 2008
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Beneficial Effects of Adalimumab on Biomarkers Reflecting Structural Damage in Patients with Ankylosing Spondylitis
WALTER P. MAKSYMOWYCH, PROTON RAHMAN, KAM SHOJANIA, WOJCIECH P. OLSZYNSKI, GLEN T.D. THOMSON, SHAILA BALLAL, ROBERT L. WONG, ROBERT D. INMAN
The Journal of Rheumatology Oct 2008, 35 (10) 2030-2037;

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Beneficial Effects of Adalimumab on Biomarkers Reflecting Structural Damage in Patients with Ankylosing Spondylitis
WALTER P. MAKSYMOWYCH, PROTON RAHMAN, KAM SHOJANIA, WOJCIECH P. OLSZYNSKI, GLEN T.D. THOMSON, SHAILA BALLAL, ROBERT L. WONG, ROBERT D. INMAN
The Journal of Rheumatology Oct 2008, 35 (10) 2030-2037;
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