Concentration-effect relationship of hydroxychloroquine in rheumatoid arthritis--a cross sectional study.

OBJECTIVE: To determine the relationship between hydroxychloroquine concentration and effect in patients with rheumatoid arthritis (RA).
METHODS: Using a cross sectional study design, drug concentration and effect were measured at one time. Forty-three patients with RA, receiving hydroxychloroquine therapy for at least 6 months and not receiving glucocorticosteroids, gold or penicillamine therapy were enrolled. The main outcome measures were hydroxychloroquine concentration and disease activity measured as degree of synovitis, pain, duration and intensity of morning stiffness, impairment of activities of daily living, patients' and physicians' subjective assessment of disease, erythrocyte sedimentation rate, and rheumatoid factor (RF). Hemoglobin and albumin concentrations were also recorded.
RESULTS: Patients with none or mild intensity of morning stiffness, those with stiffness lasting less than 0.5 h and those with negative RF had significantly higher hydroxychloroquine blood concentrations than those in whom these measures indicated a more active disease (Mann-Whitney U test, p < 0.05). Similar trends were recorded for 3 other disease activity measures (p = 0.12-0.24). Analysis of all 9 individual disease activity measures indicated that the groups with less active disease had higher mean blood concentrations of hydroxychloroquine than those with measures indicating more active disease (p < 0.01).
CONCLUSION: Our data provide the first evidence of a concentration-response relationship for hydroxychloroquine in RA for individual disease activity measures. However, an unweighted summed score of disease activity did not correlate significantly with drug blood concentrations. A prospective study is necessary to confirm the relationship and to determine a therapeutic concentration range.