Clinical trial NCT03187743: Personalised Pharmacological Approach to the Tapering of Corticosteroid Doses in Systemic Lupus Patients Treated With Prednisone
Official title: Personalised Pharmacological Approach to the Tapering of Corticosteroid Doses in Systemic Lupus Patients Treated With Prednisone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Lupus Erythematosus, Systemic
Keywords: Lupus erythematosus
Systemic
Corticosteroid
Prednisone
Pharmacokinetics
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2017-06-15
Enrollment: 72
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: SELENA-SLEDAI score
timeFrame: 3 months
Secondary outcomes:
measure: Primary parameters : volume of distribution
timeFrame: Day 0, 1 month, 3 months
measure: Primary parameters : elimination clearance
timeFrame: Day 0, 1 month, 3 months
measure: Primary parameters : absorption constant
timeFrame: Day 0, 1 month, 3 months
measure: Secondary parameters : trough concentration
timeFrame: Day 0, 1 month, 3 months
measure: Secondary parameters : maximum concentration
timeFrame: Day 0, 1 month, 3 months
measure: Secondary parameters : Area Under Curve (AUC)
timeFrame: Day 0, 1 month, 3 months
measure: Secondary parameters : elimination half-life
timeFrame: Day 0, 1 month, 3 months
measure: Occurrence of adverse events
timeFrame: 3 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hospital Necker Enfants Malades
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Michaela SEMERARO
role: STUDY_DIRECTOR
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