Personalised Pharmacological Approach to the Tapering of Corticosteroid Doses in Systemic Lupus Patients Treated With Prednisone
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- SELENA-SLEDAI score
研究概览
简要总结
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
详细描述
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 :
- 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
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Pharmacokinetics/dynamics
Blood samples at 3 visits
干预措施: Blood samples (Other)
结局指标
主要结局
SELENA-SLEDAI score
时间窗: 3 months
次要结局
- Primary parameters : volume of distribution(Day 0, 1 month, 3 months)
- Primary parameters : absorption constant(Day 0, 1 month, 3 months)
- Secondary parameters : trough concentration(Day 0, 1 month, 3 months)
- Secondary parameters : maximum concentration(Day 0, 1 month, 3 months)
- Secondary parameters : elimination half-life(Day 0, 1 month, 3 months)
- Primary parameters : elimination clearance(Day 0, 1 month, 3 months)
- Secondary parameters : Area Under Curve (AUC)(Day 0, 1 month, 3 months)
- Occurrence of adverse events(3 months)