Concentration-effect relationship of hydroxychloroquine in patients with rheumatoid arthritis - A prospective, dose ranging study

Objective. A 6 month prospective randomized double blind study was conducte d to investigate hydroxychloroquine dose concentration-effect relationships in people with rheumatoid arthritis. Methods. Patients were randomized in 2 groups: one group received 200 mg hy droxychloroquine sulfate daily (A) and one group received 400 mg daily (B). Each month, 8 disease variables were assessed, adverse events recorded, an d hydroxychloroquine blood concentrations determined. Results. Twenty-three patients were included: 10 in group A and 13 in group B. After 6 months of therapy, a significant improvement in disease activit y was noted for 6 criteria with no statistical differences between groups: pain (assessed by a visual analog scale), joint scores (swelling and tender ness), impairment in daily Living activity (18 activities graded 0 to 8), p atient assessment of disease state, and erythrocyte sedimentation rate. Hyd roxychloroquine steady-state blood concentrations (Month 6) were significan tly different between groups (mean +/- SD): 450.6 +/- 285.3 ng/ml (A) vs 87 0.3 +/- 329.3 ng/ml(B) (p = 0.0001). Steady-state concentrations were corre lated with the daily dose (r = 0.63, p = 0.005), the improvement in activit y of daily living (r = 0.49, p = 0.03), and the improvement in joint tender ness score (r = 0.47, p = 0.038). Conclusion. The data indicate that hydroxychloroquine is an effective thera py, but there were no further improvements observed in the group receiving 400 mg daily compared to those receiving 200 mg. There were some correlatio ns between hydroxychloroquine steady-state blood concentrations and effects .