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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, and ROBERT D. INMAN, for the M03-606 Study Group
ABSTRACT. 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 adalimumab 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. (J Rheumatol First Release Sept 1 2008) Key Indexing Terms:
ANKYLOSING SPONDYLITIS From the Department of Medicine, University of Alberta, Edmonton, Alberta; Department of Medicine, Memorial University, St. John's, Newfoundland; Department of Medicine, University of British Columbia, Vancouver, British Columbia; University of Saskatchewan, Regina, Saskatchewan; Centre for Inflammatory and Arthritis Disease Studies, University of Manitoba, Winnipeg, Manitoba, Canada; Abbott Laboratories, Parsippany, New Jersey, USA; and Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Supported by Abbott Laboratories. Prof. Maksymowych is a Scientist of the Alberta Heritage Foundation for Medical Research. 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. Address reprint requests to Prof. W.P. Maksymowych, Department of Medicine, 562 Heritage Medical Research Building, University of Alberta, Edmonton, Alberta T6G 2S2. E-mail: walter.maksymowych@ualberta.ca Accepted for publication May 21, 2008.
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