Very low blood hydroxychloroquine concentration as an objective marker of poor adherence to treatment of systemic lupus erythematosus

Abstract

Background: Poor adherence to treatment is difficult to diagnose accurately. Hydroxychloroquine (HCQ) has a long elimination half-life and its concentration in whole blood can be measured easily. Objective: To evaluate the utility of a very low blood HCQ concentration as a marker of poor compliance in patients with systemic lupus erythematosus (SLE). Methods: HCQ concentrations were determined on a blinded basis in 203 unselected patients with SLE. At the end of the study, the patients were informed of the results and retrospectively interviewed about their adherence to treatment. Results: 14 (7%) patients said that they had stopped taking HCQ (n = 8) or had taken it no more than once or twice a week (n = 6). Their mean (SD) HCQ concentration was 26 (46) ng/ ml. range (0-129 ng/ml) By contrast, the other patients had a mean HCQ concentration of 1079 ng/ml range (205-2629 ng/ml). The principal barriers to adherence were related to HCQ treatment characteristics. Adherence subsequently improved in 10 of the 12 patients whose blood HCQ concentrations were remeasured. Conclusions: Very low whole-blood HCQ concentrations are an objective marker of prolonged poor compliance in patients with SLE. Regular drug assays might help doctors in detect noncompliance and serve as a basis for counselling and supporting these patients.

Photoprotective effects of a broad-spectrum sunscreen in ultraviolet-induced cutaneous lupus erythematosus: A randomized, vehicle-controlled, double-blind study

“…[13][14][15]24 Moreover, some patients received antimalarials up to 6 weeks before the start of the study; these agents have a long terminal elimination half-life of more than 40 days. 37 The differences between the results in the vehicletreated and untreated areas might further be because of the fact that the vehicle might function as a physical sun blocker applied in an amount of 2 mg/cm 2 before phototesting. However, the number of patients with different CLE subtypes, such as SCLE, included in the study is too small to detect differences between the vehicle-treated and untreated areas.…”

Hydroxychloroquine and smoking in patients with cutaneous lupus erythematosus

“…33,42 It is well established that low blood hydroxychloroquine concentrations are associated with SLE disease activity, are a strong predictor of exacerbations, 43 and may help to diagnose poor adherence. 44 However, the association between hydroxychloroquine concentration and smoking is less clear. A 2007 study quantified hydroxychloroquine levels by high performance liquid chromatography, 45 and similar mean blood hydroxychloroquine concentrations were found in active smokers and nonsmokers.…”

Hydroxychloroquine directly reduces the binding of antiphospholipid antibody–β2-glycoprotein I complexes to phospholipid bilayers

“…20 The actual concentration of the drug at membranes and organelles where it is bound is not known and may possibly be higher. HCQ is sequestered in a storage compartment, as demonstrated by the prolonged terminal elimination half-life in healthy volunteers of more than 40 days, and the fact that a treatment period of 6 months is required to achieve steady-state levels.…”

“…HCQ concentrations of 1 g/mL and greater were used for these experiments because the mean blood concentration of drug in SLE patients who comply with treatment was reported to be in that range. 20 We also investigated the effects of HCQ on clinical assays that are used for diagnosis of APS, the anticardiolipin IgG, anti-␤2GPI IgG, and the dilute Russell viper venom time (dRVVT). …”