Salivary hydroxychloroquine levels: relevance in juvenile systemic lupus erythematosus (JSLE) disease activity and renal disease activity in adult systemic lupus erythematosus

Abstract

There is a large variability in drug response that can be attributed in part to the patient’s lack of adherence to treatment. Low adherence is common and can reach 30% of prescriptions in general and 50% in chronic diseases. Several self-report questionnaires are used to assess adherence, however, their use in clinical practice has been quite limited. Hydroxychloroquine (HCQ) has an exceptional immunomodulatory role in systemic lupus erythematosus (SLE), and subtherapy or withdrawal are associated with disease outbreaks. In adult SLE, whole blood concentrations below than 1000 ng/mL of HCQ have been reported to be associated with disease activity and is considered a strong predictor of exacerbation in the subsequent six months. Monitoring of drug or metabolite levels in biological fluids is a useful tool for adherence assessment and clinical decision making. In the area of rheumatology, there are few studies of monitoring of circulating drug levels. This monitoring is still restricted to blood dosage. On the other hand, saliva is an alternative matrix suggested for individualization and optimization of therapy in chronic diseases, because of its non-invasive obtention, less complex compared to conventional matrices and generally offers a good correlation with the serum free drug. However, few studies have explored the potential for monitoring drugs in this matrix, in part due to the low sensitivity of available quantitative bioanalytical methods. The recent development of tandem mass spectrometers has enabled the measurement of very low drug concentrations in small volumes of unconventional matrices. To date, there are no studies in the literature on monitoring saliva hydroxychloroquine levels in SLE patients. Therefore, the present project aims to evaluate the relevance of hydroxychloroquine and its main metabolites salivary level in the monitoring of efficacy, toxicity and treatment adherence in juvenile systemic lupus erythematosus and in the renal activity of systemic lupus erythematosus in adults.