This study evaluated measures of
metalloproteinase gene expression in synovial biopsies as a means of differentiating the activities of two antirheumatic
therapies:
piroxicam and
tenidap. Synovial biopsies and quantitative in situ hybridization for
stromelysin (STR),
collagenase (COL),
tissue inhibitor of metalloproteinase-1 (TIMP), and actin
mRNA were performed in a subset of patients with
rheumatoid arthritis in a larger doubleblind randomized crossover trial comparing 120 mg/day of
tenidap for 6 weeks with 20 mg/day of
piroxicam for 6 weeks. There were no consistent differences between
tenidap and
piroxicam on COL or TIMP
mRNA expression, but STR
mRNA was significantly lower after
tenidap compared with
piroxicam (p = 0.037). There were no significant associations between measures of local or systemic clinical activity and STR, COL, or TIMP gene expression. However, changes in STR gene expression were significantly correlated with changes in serum
C-reactive protein (p = 0.016). Because
tenidap and
piroxicam are both potent inhibitors of
prostaglandin production, the effect of
tenidap on STR gene expression may be due to its additional
cytokine modulating activity. Clinical trials with data from synovial biopsies may be useful in evaluating the potential for disease-modifying effects of
antirheumatic drugs.