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

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 include...

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Bibliographic Details
Published in:Journal of rheumatology 2008-10, Vol.35 (10), p.2030-2037
Main Authors: MAKSYMOWYCH, Walter P, RAHMAN, Proton, SHOJANIA, Kam, OLSZYNSKI, Wojciech P, THOMSON, Glen T. D, BALLAL, Shaila, WONG, Robert L, INMAN, Robert D
Format: Article
Language:English
Subjects:
Adalimumab
Adult
Antibodies, Monoclonal - therapeutic use
Antibodies, Monoclonal, Humanized
Biological and medical sciences
Biomarkers - blood
Biomarkers - urine
C-Reactive Protein - analysis
Collagen Type I - blood
Collagen Type II - urine
Diseases of the osteoarticular system
Diseases of the spine
Female
Humans
Immunomodulators
Inflammatory joint diseases
Male
Matrix Metalloproteinase 3 - blood
Medical sciences
Middle Aged
Peptides - blood
Pharmacology. Drug treatments
Severity of Illness Index
Spondylitis, Ankylosing - blood
Spondylitis, Ankylosing - drug therapy
Spondylitis, Ankylosing - urine
Tumor Necrosis Factor-alpha - antagonists & inhibitors
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Summary: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
ISSN:0315-162X
1499-2752