Equianalgesic effects of paracetamol and indomethacin in rheumatoid arthritis

The therapeutic and adverse effects of 2 weeks of treatment with high-dose indomethacin (150 mg/day) were compared with those of low-dose indomethacin (50 mg/day) combined with paracetamol (4 g/day) in a double-blind, double-dummy, cross-over study in 17 patients with active rheumatoid arthritis. Grip strength, Ritchie's index, joint circumference, joint pain, and patient's and physician's global assessments were estimated, and conventional laboratory parameters were followed. In addition, the time-concentration profiles of indomethacin and paracetamol were assessed during steady state. All patients had measurable plasma drug levels, indicating adequate compliance, and responders and nonresponders (five on each treatment) had equal drug levels, indicating that the variation in therapeutic efficacy was not secondary to pharmacokinetic differences. While there were fewer and milder side-effects during treatment with the drug combination, there was no difference in therapeutic efficacy. Hence, it appears that the main therapeutic profit of indomethacin in daily doses greater than 50 mg is enhanced analgesia. As such dosage involves pronounced side-effects, it seems more appropriate to employ the combination of 50 mg indomethacin and 4 g paracetamol, whereby similar analgesia can be obtained without an increase in side-effects.