Rheumatoid arthritis treated with tenidap and piroxicam. Clinical associations with cytokine modulation by tenidap.
OBJECTIVE
To compare the effects of tenidap and piroxicam on acute-phase protein and cytokine levels in the blood of rheumatoid arthritis (RA) patients and to explore their associations with clinical disease activity.


METHODS
A double-blind, randomized, crossover trial in 49 patients with active RA compared 6 weeks of treatment with tenidap (120 mg/day) versus 6 weeks of treatment with piroxicam (20 mg/day).


RESULTS
Median values for C-reactive protein (CRP), Westergren erythrocyte sedimentation rate (ESR), serum amyloid A (SAA) protein, and interleukin-6 (IL-6) were significantly lower after tenidap treatment compared with piroxicam treatment, even in the presence of stable background treatment with prednisone, methotrexate, or prednisone plus methotrexate. The median within-patient treatment differences (after tenidap minus after piroxicam) in the CRP, ESR, SAA, and IL-6 values were -1.7 mg/dl, -10.0 mm/hour, -22.0 micrograms/ml, and -3.7 pg/ml, respectively, and represent -60.4%, -17.7%, -35.5%, and -26.1% of the respective baseline levels. IL-6 levels were positively correlated with CRP and SAA. Plasma IL-1 beta was generally below the level of detection. Tumor necrosis factor alpha levels were similar after tenidap and after piroxicam. Treatment differences for 4 of 7 clinical parameters favored tenidap, but did not reach statistical significance. IL-6, CRP, and ESR were significantly correlated with clinical treatment differences. Tenidap and piroxicam toleration were similar, although tenidap-treated patients exhibited a reversible increase in urinary protein excretion.


CONCLUSIONS
Tenidap was differentiated from piroxicam by lower levels of acute-phase proteins, ESR, and IL-6 after tenidap treatment. These treatment differences were significantly correlated with clinical parameters.
Littman
B H
BH
Central Research Division, Pfizer Inc., Groton, CT 06340.
Drury
C E
CE
Zimmerer
R O
RO
Stack
C B
CB
Law
C G
CG
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D018592:Cross-Over Studies; D016207:Cytokines / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D000078183:Oxindoles; D010147:Pain Measurement; D010894:Piroxicam / Q000627:therapeutic use*; D011507:Proteinuria / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D007211:Indoles; D007375:Interleukin-1; D015850:Interleukin-6; D000078183:Oxindoles; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; D010894:Piroxicam; D002097:C-Reactive Protein; C062866:tenidap