The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS

The main objective of study PLUS is to determine the potential benefits of individualized HCQ dosing schedules aimed at maintaining the whole-blood HCQ concentration above 1000 ng/ml

Hydroxychloroquine (HCQ) is a treatment which allows preventing Systemic Lupus Erythematosus (SLE) exacerbations.

HCQ can be measured in whole-blood by HPLC (High Performance Liquid Chromatography).

Interindividual variability in blood HCQ concentrations is important and a correlation between HCQ level and clinical efficacy of HCQ has been demonstrated in SLE in a monocentric study of 143 unselected SLE patients.

The main objective of study PLUS is to determine the potential benefits of individualized HCQ dosing schedules aimed at maintaining the whole-blood HCQ concentration above 1000 ng/ml

The secondary objectives are:

* To define biological and clinical hallmarks present at M1 (month 1) which are predictor of SLE exacerbations in the next 6 month,
* To establish the parameters of HCQ pharmacokinetic model, by a study of population, using a "Bayésienne" approach.
* To study the influence of allelic variants of drug carriers and other genes in the interindividual variability of blood HCQ concentrations.
* To study the influence of the compliance in the blood HCQ concentration variability
* To study the relation between blood HCQ concentrations, SLE activity and quality of life
* To study the relation between blood HCQ concentrations, SLE activity and lipid profile of the patients
* To study the relation between ECG abnormalities and blood HCQ concentrations
* To constitute a bank of serum, a DNAbank, and a RNAbank to permit subsequent studies

Eligibility Criteria:
Inclusion Criteria:

* Age of 18 and above
* Diagnosis of Systemic Lupus Erythematosus (SLE) according to the American College of Rheumatology (ACR) Classification Criteria.
* Treatment with HCQ for at least 6 months, without modification of HCQ dosage for 2 months
* Stable dosage of HCQ from one day to another (200 g x 2/day or 400 mg once a day or 200 mg once a day)
* No increase in the steroids dosage during the 3 previous weeks
* Steroids dosage lower or equal to 0. 5 mg/kg/day of prednisone equivalent
* No modifications of a possible immunosuppressor during the 2 previous months
* SELENA-SLEDAI \< or = 12
* Signature of the consent of participation

Exclusion Criteria:

* Known retinopathy, present or passed
* Severe cataract obstructing the ophthalmologic monitoring
* MONOPHTALM patients
* Past history of intolerance with HCQ (in particular gastro-intestinal, or retinal) during the possible former use of a higher dosage
* Use of nivaquine during the 3 previous months
* Treatment with biotherapy (for example Rituximab) during the 12 previous months
* Calculated clearance of creatinin lower than 60 ml/min
* Chronic alcoholism
* Liver failure
* Desire of pregnancy in the next 7 months
* Known non compliance, and risks of random follow-up
* Absence of social security cover

People profiting from a particular protection:

* Pregnant women
* Age under 18
* Patient under supervision and TRUSTEESHIP
* People who are hospitalized without their consent and not protected by the law
* People who are private of freedom.

Criteria of inclusion at the visit of randomization (D0):

All the patients responding to the next criterions can be randomized:

* Blood HCQ concentration ranging between 100 and 750 ng/ml at the time of the visit of preselection,
* No increase in the steroids dosage since last visit
* No modifications of a possible immunosuppressor since last visit
* SELENA-SLEDAI \< or = 12 Activity of the lupus remaining stable (no increase of more than 2 points of the SELENA-SLEDAI),
* Ophthalmologic examination in the 6 previous months with no contra-indication for the use of HCQ,
* Absences of conductive disorders on the ECG
* Use of an effective contraception,
* Negative Beta-HCG.