Serum levels of MMP-3 and cathepsin K in patients with ankylosing spondylitis: effect of TNFalpha antagonist therapy.

OBJECTIVE: To measure serum levels of MMP-3 and cathepsin K in patients with ankylosing spondylitis (AS) and in controls and to look for changes in these variables during TNFalpha antagonist therapy.
METHODS: We prospectively studied a group of patients who met New York criteria for AS and a group of healthy volunteers. We recorded age, disease duration, main features of the disease, BASDAI, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Serum MMP-3 and cathepsin K were assayed in duplicate using ELISA kits (Quantikine MMP-3, R&D Systems; and Cathepsin K, Biomedica). We also assayed IL-17 (Quantikine IL-17, R&D Systems) and BMP-7 (human BMP-7 DuoSet, R&D Systems). In patients treated with TNFalpha antagonists, the assays were repeated 10 weeks after treatment initiation. The Mann-Whitney test was used for between-group comparisons and the Wilcoxon test for evaluations of changes under treatment. Correlation testing was performed. P-values less than 0.05 were considered significant.
RESULTS: We studied 23 outpatients with AS and 21 controls, with mean age of 39.9 years and 41.2 years, respectively (NS). Disease duration was 10.1 years (1.3); most patients had axial disease (n=21) and carried HLA-B27 (n=19). At baseline, the mean BASDAI was 44.1 mm (4.1) and the mean CRP level was 22.3 mg/L (4.7). Serum MMP-3 levels were significantly higher in the patients than in the controls (4.71 vs. 2.79 ng/ml, P=0.04); levels were also higher for cathepsin K (6.4 vs. 3.6 pg/ml) and IL-17 (60.4 vs. 32 pg/ml), but the differences were not statistically significant. No difference was noted for BMP-7. The only positive correlation was between the ESR and the CRP level (P=0.0002). Thirteen patients were evaluated 10 weeks into TNFalpha antagonist therapy (adalimumab, n=7; etanercept, n=4; or infliximab, n=2). Serum MMP-3 decreased significantly (P=0.04); significant decreases were also noted for the ESR, CRP, and BASDAI.
CONCLUSION: MMP-3 is significantly increased in patients with active AS but fails to correlate significantly with conventional variables used to assess disease activity. TNFalpha antagonist therapy induces a significant decrease in MMP-3 levels, together with decreases in conventional variables (ESR, CRP, and BASDAI). MMP-3 may be a biomarker for disease activity in AS but supplies no additional information to the clinician.