- Paper Report
- Open Access
Anti-tumour necrosis factor (TNF)-α therapy (etanercept)
- Maya Buch1
© Biomed Central Ltd 2002
- Received: 27 June 2002
- Accepted: 15 August 2002
- Published: 22 August 2002
- Rheumatoid arthritis
- Tumour Necrosis Factor-α
The role of tumour necrosis factor (TNF)-α in rheumatoid arthritis (RA) pathogenesis is clearly recognised as is the benefit of its blockade. Its effects include release of enzymes involved in extracellular matrix degradation (matrix metalloproteinases or MMPs), such as stromelysin 1 (MMP-3) and collagenase 1 (MMP-1). Tissue inhibitor of matrix metalloproteinase (TIMP)-1 partly regulates MMP action. In RA an imbalance between MMP and TIMP activity has been suggested.
Infliximab was previously shown to reduce serum levels of MMP-1 and MMP-3. In the current study the authors studied whether etanercept (25mg subcutaneously twice weekly) similarly modulated serum MMP as well as TIMP levels, and also whether it modulated synovial expression of these mediators.
Of the 60 patients studied 78% achieved ≥ ACR20 response (some on additional Disease-modifying antirheumatic drugs [DMARDs]). ELISA measurements showed that median serum MMP-3 and MMP-1 levels were significantly decreased at 8 and 12 weeks after treatment. TIMP-1 was downregulated only after 8 weeks. Hence the significant reduction at 12 weeks in MMP-1:TIMP-1 and MMP-3:TIMP-1 ratios can only be attributed to the downregulation of serum MMP-1 and -3 respectively rather than significant changes in TIMP levels. Baseline serum levels of MMP-3 and TIMP-1 correlated with baseline C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Additionally, baseline MMP-3 correlated with change in DAS28 score after 12 weeks of therapy.
Synovial MMP-1, MMP-3 and TIMP-1 expression showed no change with therapy.
ELISA, Immunohistochemical analysis, Computerised image analysis.