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 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<or=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<or=0.005). Change in CTX-II at 12 weeks also correlated significantly with change in MMP-3 (r=0.41; p<0.0001).


CONCLUSIONS
Adalimumab suppresses biomarkers that reflect matrix turnover in patients with AS.
Maksymowych
Walter P
WP
Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. walter.maksymowych@ualberta.ca
Rahman
Proton
P
Shojania
Kam
K
Olszynski
Wojciech P
WP
Thomson
Glen T D
GT
Ballal
Shaila
S
Wong
Robert L
RL
Inman
Robert D
RD
D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002097:C-Reactive Protein / Q000032:analysis; D024042:Collagen Type I / Q000097:blood; D024043:Collagen Type II / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D008875:Middle Aged; D010455:Peptides / Q000097:blood; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D024042:Collagen Type I; D024043:Collagen Type II; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; C052929:collagen type I trimeric cross-linked peptide; D002097:C-Reactive Protein; D019278:Matrix Metalloproteinase 3; D000068879:Adalimumab