CONCENTRATION-EFFECT RELATIONSHIP OF HYDROXYCHLOROQUINE IN RHEUMATOID-ARTHRITIS - A CROSS-SECTIONAL STUDY

Objective. To determine the relationship between hydroxychloroquine co ncentration and effect in patients with rheumatoid arthritis (RA). Met hods. Using a cross sectional study design, drug concentration and eff ect were measured at one time. Forty-three patients with RA, receiving hydroxychloroquine therapy for at feast 6 months and not receiving gl ucocorticosteroids, gold or penicillamine therapy were enrolled. The m ain outcome measures were hydroxychloroquine concentration and disease activity measured as degree of synovitis, pain, duration and intensit y of morning stiffness, impairment of activities of daily living, pati ents' and physicians' subjective assessment of disease, erythrocyte se dimentation rate, and rheumatoid factor (RF). Hemoglobin and albumin c oncentrations 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 hydroxychlo roquine blood concentrations than those in whom these measures indicat ed a more active disease (Mann-Whitney U test, p <0.05). Similar trend s 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 concentratio ns of hydroxychloroquine than those with measures indicating more acti ve 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 summ ed 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.