RT Journal Article
SR Electronic
T1 Decrease in serum level of matrix metalloproteinases is predictive of the disease-modifying effect of osteoarthritis drugs assessed by quantitative MRI in patients with knee osteoarthritis
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 2095
OP 2101
DO 10.1136/ard.2009.122002
VO 69
IS 12
A1 J-P Pelletier
A1 J-P Raynauld
A1 J Caron
A1 F Mineau
A1 F Abram
A1 M Dorais
A1 B Haraoui
A1 D Choquette
A1 J Martel-Pelletier
YR 2010
UL http://ard.bmj.com/content/69/12/2095.abstract
AB Objectives To explore the impact of disease-modifying osteoarthritis drug (DMOAD) treatment on biomarker levels and their correlation with cartilage volume loss and disease symptoms in a 2-year phase III clinical trial in patients with knee OA. Methods 161 patients with knee OA (according-to-protocol population) were selected from a 2-year DMOAD trial studying the effect of licofelone (200 mg twice daily) versus naproxen (500 mg twice daily). Clinical evaluation of patients was carried out using the Western Ontario and McMaster Universities (WOMAC) questionnaire. Biomarker measurements of matrix metalloproteinase (MMP)-1, MMP-3, interleukin (IL)-6, C reactive protein (CRP), cartilage oligomeric matrix protein (COMP) and type I collagen C-terminal telopeptide (CTX-I) in serum, type II collagen C-terminal telopeptide (CTX-II) in urine, and knee MRI were performed at baseline and 2 years. Results Over time an increase occurred in all biomarker levels with the exception of IL-6, CRP and CTX-II which decreased. The increase in MMP-1 and MMP-3 was significantly less (p=0.05; p<0.01, respectively) in the licofelone group. The baseline MMP-1 level was significantly but inversely predictive of cartilage volume loss for the medial compartment in both univariate (p=0.04) and multivariate (p≤0.04) regression analyses, and COMP, a predictor for the lateral compartment, in both univariate and multivariate models (p<0.01). Baseline levels of IL-6 and CRP also showed a significant relationship with volume loss for the medial compartment (univariate analysis, p=0.04 and p=0.01, respectively; multivariate analysis, p=0.03, p=0.01). A significant association (univariate) was observed between the change in the levels of MMP-1 (p=0.03) and MMP-3 (p=0.02) and cartilage volume loss (lateral compartment) over 2 years. Baseline levels of CTX-I correlated (p=0.02) with an increase in the size of the bone marrow lesion in the medial compartment. The baseline CRP levels correlated with worsening of symptoms: WOMAC total index (p<0.01), pain (p<0.01) and function (p<0.01). Conclusion Higher baseline values of IL-6, CRP and COMP are predictive of greater risk of cartilage loss in OA. However, over time a reduction in MMP-1 and MMP-3 levels correlated best with reduction in cartilage volume loss and the effect of drug treatment. Baseline CRP was found to be a good predictor of the symptomatic response to treatment.