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

J Rheumatol. 2000 Jul;27(7):1656-60.


Objective: A 6 month prospective randomized double blind study was conducted to investigate hydroxychloroquine dose concentration-effect relationships in people with rheumatoid arthritis.

Methods: Patients were randomized in 2 groups: one group received 200 mg hydroxychloroquine sulfate daily (A) and one group received 400 mg daily (B). Each month, 8 disease variables were assessed, adverse events recorded, and 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 activity was noted for 6 criteria with no statistical differences between groups: pain (assessed by a visual analog scale), joint scores (swelling and tenderness), impairment in daily living activity (18 activities graded 0 to 8), patient assessment of disease state, and erythrocyte sedimentation rate. Hydroxychloroquine steady-state blood concentrations (Month 6) were significantly different between groups (mean +/- SD): 450.6 +/- 285.3 ng/ml (A) vs 870.3 +/- 329.3 ng/ml (B) (p = 0.0001). Steady-state concentrations were correlated with the daily dose (r = 0.63, p = 0.005), the improvement in activity of daily living (r = 0.49, p = 0.03), and the improvement in joint tenderness score (r = 0.47, p = 0.038).

Conclusion: The data indicate that hydroxychloroquine is an effective therapy, but there were no further improvements observed in the group receiving 400 mg daily compared to those receiving 200 mg. There were some correlations between hydroxychloroquine steady-state blood concentrations and effects.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / drug therapy*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hydroxychloroquine / administration & dosage*
  • Hydroxychloroquine / pharmacokinetics
  • Hydroxychloroquine / toxicity
  • Male
  • Middle Aged
  • Prospective Studies
  • Treatment Outcome


  • Hydroxychloroquine