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 μg/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‐1β was generally below the level of detection. Tumor necrosis factor α 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. Conclusion. 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 clincial parameters.