A cross-sectional study of hydroxychloroquine concentrations and effects in people with systemic lupus erythematosus

To investigate the pharmacokinetics of hydroxychloroquine (HCQ) and relationships of HCQ concentration with disease activity variables (concentration-effect relationships) in patients with systemic lupus erythematosus (SLE).

HCQ concentration and disease activity were measured at a single time point in 60 patients with SLE receiving HCQ for at least 6 months. Some retrospective objective data on disease activity prior to HCQ commencement were available. Correlations were sought between HCQ blood concentrations and disease variables (Systemic Lupus Activity Measure (SLAM) scores, joint scores, morning stiffness, pain, well-being, general improvement, other medication use (including corticosteroids), and physician and patient assessments). Blood HCQ concentrations were also dichotomised into 'more' and 'less/no' disease activity, and mean blood concentrations in the two groups for each disease activity measure were compared.

The pharmacokinetics (dose-concentration relationships) of HCQ were highly variable in people with SLE. Apparent total clearance of HCQ from blood was 316 (± 319) mL/min (mean (± standard deviation). There was no correlation between SLAM score, patient global assessment or physician global assessment, and blood HCQ concentrations (r(2) = 0.2, 0.04 and 0.13, respectively; P > 0.05). However, during HCQ therapy, 64% (14 of 22 patients) had a reduction in prednisolone dose of 50% or more compared with pre-HCQ therapy.

No significant concentration-effect relationship for HCQ in the treatment of SLE was observed perhaps because consistently high enough blood HCQ concentrations were not achieved. Pharmacokinetic variability led to a wide range of blood HCQ concentrations. A concentration-targeting study for HCQ in SLE would be timely.