the reduction of systemic lupus erythematosus flares :study plus

Conditions: Systemic Lupus Erythematosus

Summary: 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.

Keywords: systemic lupus erythematosus hydroxychloroquine