Effect of tenidap on metalloproteinase gene expression in rheumatoid arthritis: a synovial biopsy study.
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.
Littman
B H
BH
Pfizer Central Research, Groton, Connecticut (B.H.L); Hospital of the University of Pennsylvania and the Veterans Administration Medical Center, Philadelphia, Pennsylvania (H.R.S.); University of California San Diego Medical Center, San Diego, California (D.L.B., M.H.W., G.S.F.).
Schumacher
H R
HR
Boyle
D L
DL
Weisman
M H
MH
Firestein
G S
GS