Effects of Etanercept and Adalimumab on Serum Levels of Cartilage Remodeling Markers in Women with Rheumatoid Arthritis

Tumor necrosis factor alpha inhibitor (TNF alpha I) therapy is associated with a significant inhibition of radiographic progression, resulting in improved physical function and quality of life among patients with rheumatoid arthritis (RA). The mechanism by which TNF alpha I prevent joint destruction is still unknown. In this study, the effect of 15-month anti-TNF-alpha therapy in combination with methotrexate on circulating levels of biochemical markers of cartilage turnover in female RA patients was assessed. Serum levels of collagen type II C-terminal cleavage neoepitope (C2C), C-terminal propeptide of type II collagen (PIICP), cartilage oligomeric matrix protein (COMP), and matrix metalloproteinase-3 (MMP-3) were evaluated using immunoassays at baseline and 15 months after the start of TNF alpha I treatment. Baseline COMP, C2C, and MMP-3 levels and C2C/PIICP ratios were significantly higher in women with RA compared with those observed in the healthy subjects. No differences in PIICP levels between the controls and the women with RA were observed. After 15 months of TNF alpha I treatment, serum levels of C2C, COMP, and MMP-3 decreased, whereas the levels of PIICP increased but were still not different from those of the controls. These changes were accompanied by significantly reduced C2C/PIICP ratios. Before the start of TNF alpha I therapy, serum levels of COMP significantly correlated with the patients' ages (p < 0.05) and their 28-joint disease activity score values based on their erythrocyte sedimentation rates (DAS28-ESR; p < 0.05). Moreover, multiple linear regression analysis showed that baseline COMP levels retained a significant association with DAS28-ESR value (beta = 287.74, p = 0.022, R-2 model = 0.25) after model adjustments. The largest area under the ROC curve was obtained for C2C/PIICP ratios (AUC: 0.830, 95% CI: 0.727-0.932, p < 0.001). Our results suggest that long-term anti-TNF-alpha therapy combined with MTX has a beneficial effect on cartilage remodeling that is associated with clinical improvement among RA patients. Serum C2C/PIICP ratios may help to monitor the effectiveness of anti-TNF-alpha treatment among RA patients.

Automated summary

Tumor necrosis factor alpha inhibitor (TNF alpha I) therapy, combined with methotrexate, can effectively inhibit radiographic progression and improve physical function and quality of life among patients with rheumatoid arthritis (RA). The study evaluated the effect of 15-month anti-TNF-alpha therapy on cartilage turnover markers in female RA patients and found significant changes in serum levels of biochemical markers and ratios. Baseline COMP levels were associated with disease activity and could be used as a predictor. The C2C/PIICP ratio showed promising potential as a biomarker for monitoring the effectiveness of anti-TNF-alpha treatment.