Routine Hydroxychloroquine Blood Concentration Measurement in Systemic Lupus Erythematosus Reaches Adulthood.

Abstract

The benefits of hydroxychloroquine (HCQ) treatment in patients with systemic lupus erythematosus (SLE) are now clearly recognized and it has been highly recommended that all patients with SLE should be prescribed this drug1. One less well-known benefit of HCQ is related to its pharmacokinetic properties (i.e., its long half-life) and to the availability of a blood assay to measure its blood concentration. Indeed, HCQ and its metabolite levels can be quantified by high performance liquid chromatography, which is available in many centers because this type of equipment is required to monitor other drugs (antidepressants, tyrosine kinase inhibitors, antibiotics, etc.). Methods of dosage may vary slightly, but for reasons of sensitivity and reproducibility, blood HCQ concentrations ([HCQ]) should be measured in whole blood (minimum 1 ml blood sampled in EDTA or in lithium heparinate tubs). In the 1980s, Tett, et al first described this method and studied the importance of [HCQ] measurement in patients with rheumatoid arthritis (RA). They first showed that there was a great variability in [HCQ] among individuals, including in healthy volunteers and adherent patients2,3. They also found a significant, although weak, correlation between [HCQ] and clinical efficacy in RA [corresponding to the so-called pharmacokinetic/pharmacodynamic (PK-PD) effect]3,4. These data were later confirmed by Munster, et al 5. When this blood measurement became available in our center in 2000, we decided to evaluate the PK-PD relationship of HCQ in patients with SLE. Among 143 unselected patients with SLE who were all receiving 400 mg/day of HCQ, the mean [HCQ] on day 0 was 1017 ± 532 ng/ml with more than a 10-fold range of drug concentrations found after similar doses6. We observed that low [HCQ] were associated with increased disease activity, and that low baseline [HCQ] … Address correspondence to Dr. N. Costedoat-Chalumeau, Hopital Cochin, 75014, Paris, France. E-mail: nathalie.costedoat{at}gmail.com