Factors Related to Blood Hydroxychloroquine Concentration in Patients With Systemic Lupus Erythematosus

Abstract

Objective To identify factors associated with blood concentrations of hydroxychloroquine (HCQ) and its major metabolite, N‐desethylhydroxychloroquine (DHCQ), in patients with systemic lupus erythematosus (SLE; lupus) receiving long‐term oral HCQ treatment. Methods SLE patients who had been taking HCQ for more than 3 months were recruited. Various clinical characteristics, laboratory values, and SLE Disease Activity Index (SLEDAI) scores were examined. The concentrations of HCQ and DHCQ ([HCQ] and [DHCQ]) were measured by liquid chromatography mass spectrometry, and the relationship between [HCQ], [DHCQ], and [HCQ]:[DHCQ] ratio to various factors was investigated. Results In total, 189 SLE patients receiving long‐term HCQ treatment were included in the analysis. The median (interquartile range [IQR]) [HCQ] was 515 (IQR 353–720) ng/ml, the median [DHCQ] was 417 (IQR 266–591) ng/ml, and the median [HCQ]:[DHCQ] ratio was 1.3 (range 1.0–1.7). [HCQ] was closely associated with [DHCQ] (r = 0.81, P < 0.0001). The weight‐adjusted oral HCQ dose was strongly associated with both [HCQ] (P < 0.001) and [DHCQ] (P < 0.001). Time since last dose was associated with [HCQ] (P < 0.001). No statistically significant association was found between renal function or smoking and [HCQ] or [DHCQ]. Use of additional immunosuppressants increased both [HCQ] and [DHCQ] after adjusting for possible confounders (P = 0.04 and P = 0.03, respectively). The lower SLEDAI score was significantly related to higher [HCQ], after adjusting for age, sex, weight‐adjusted HCQ dose, time since last dose, number of other immunosuppressants, and smoking status (P = 0.007). Conclusion Various factors affected blood levels of [HCQ], [DHCQ], or the [HCQ]:[DHCQ] ratio of SLE patients receiving long‐term oral HCQ treatment. Notably, higher [HCQ] was associated with a lower SLEDAI score in our typical outpatient clinic population with lupus.