Personalised Pharmacological Approach to the Tapering of Corticosteroid Doses in Systemic Lupus Patients Treated With Prednisone
Personalised Pharmacological Approach to the Tapering of Corticosteroid Doses in Systemic Lupus Patients Treated With Prednisone
This research study is a multicentre prospective pharmacokinetic study. The clinical and
 biological data will be collected in the framework of a prospective study. The drug to be
 evaluated is a glucocorticoid routinely used to treat Systemic lupus erythematosus (SLE)
 patient. Initial dose of prednisone must be oral and at least 0.5mg/Kg/day, but the precise
 dosage and the tapering regimen will be determined according to the clinical judgment of the
 investigator. The duration of the research period for each patient will be 3 months. Three
 visits (which are all usual care visits) will be needed within the 3 months of the study for
 collecting data and/or blood sampling
Until now, glucocorticoids always play a leading role in the lupus treatment, and the lupus's
 prognosis has been greatly improved by the treatment of serious flare-ups with a combination
 of high-dose corticosteroids and immunosuppressants, notably mycophenolate mofetil (MMF)
 together with hydroxychloroquine (Plaquenil), survival at 10 years being 70 to 90%. However,
 corticosteroid treatment is also a major cause of morbidity and mortality, and with 60 years
 of experience, consensus about "appropriate" dosages, route of administration and tapering
 regimes has not been reached. In addition, there is a large variability in clinical response
 to corticosteroid therapy which may be attributed to heterogeneity of SLE, drugs interaction
 or to environmental and genetic factors, especially to polymorphism of the MDR (multi-drug
 resistance) -1 and NR3C1 (glucocorticoid nuclear receptor subfamily 3, group C, member 1).
 There are no previous studies investigating the role of MDR-1 and NR3C1 genes polymorphisms
 in the response to corticosteroids in lupus patients Drug monitoring of immunosuppressive
 drugs has been largely explored in renal transplantation and in a lesser extend in SLE
 (especially for mycophenolic acid). Relationship between prednisolone PK and clinical
 efficacy/toxicity have been also shown previously especially in renal transplant population.
 In patients with SLE, only two small series (8 children, 25 adults) have explored this
 relationship, and suggested that SLE activity and corticosteroid toxicity might be related to
 prednisolone AUC. Thus, limited data suggest that prednisone monitoring may optimize
 treatment efficacy and minimize adverse events.

 The DECOR study will aim :

 1. to search for relationship between prednisolone PK and SLE disease activity in a large
 series of patients in order to improve the rational of prednisone doses in lupus
 patients

 2. to identify pharmacogenetic factors influencing the response to steroid in order to
 identify patients sharing a high probability of being responders or resistant to
 corticosteroids.

 This approach could be applied to all inflammatory diseases requiring prolonged
 corticosteroid treatment, and thus, be a major progress in the use of this old treatment.
Inclusion Criteria:

 -  Patient aged ≥ 6 years

 -  Patient who met the American College of Rheumatology criteria (ACR) or the Systemic
 Lupus International Collaborating Clinics Classification (SLICC) for systemic lupus
 erythematosus.

 -  Patients needs (re)initiation of oral prednisone regimen at least at 0.5 mg/Kg/d(or
 >30mg/d for patients >60 kg) in combination with mycophenolate mofetyl or mycofenolic
 acid or cyclophosphamide at usual dose including :

 i) patient who receives bolus of methylprednisolone the week before and/or the week
 after inclusion for treating the lupus flare ii) patient who was previously treated by
 a low-prednisone dose (≤ 7.5 mg/d in patients ≥ 60 kg and ≤ 0.1 mg/kd/d in patient <
 60 kg).

 iii) patient who was previously treated by prednisone ≥ 0,5 mg/kg/d (or >30mg/d for
 patients >60 kg) but stopped since at least one month before inclusion

 -  Patient with stable doses of other immunosuppressive or biological drugs before
 inclusion (at least 15 days for Imurel, Methotrexate, Tacrolimus ; at least 6 months
 for Rituximab, Belimumab) and during the 3 months of patient participation in the
 study.

 -  Signed informed consent form by the patient (if aged ≥ 18 years), or by the parents /
 legal guardian and patient's agreement (if aged < 18 years)

 -  Patient affiliated to the health insurance system

 Exclusion Criteria:

 -  Patient presents contraindications to corticosteroids

 -  Patient presents contraindications to MMF, mycofenolic acid or cyclophosphamide for
 patient receiving immunosupressor

 -  Patient cannot be treated by oral way

 -  Patient whose physician has planned to stop prednisone in less than 3 months

 -  Patient (or parents for minor) are unable to give a written informed consent for
 physical or psychical reasons

 -  Patient disagrees with the study