NCT03187743

Personalised Pharmacological Approach to the Tapering of Corticosteroid Doses in Systemic Lupus Patients Treated With Prednisone

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 72 (actual)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 6 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Lupus Erythematosus, Systemic

Interventions

Type	Name	Description
OTHER	Blood samples	Blood samples at 3 visits : V0 : - 5 mL in heparin tube / Pharmacokinetics + Gene Expression Analysis V1 : - 5 mL in heparin tube / sample (2 to 5 samples) Pharmacokinetics + Pharmacogenetics + Gene Expression Analysis V2 : - 5 mL in heparin tube / Pharmacokinetics + Gene Expression Analysis and - 5 mL in EDTA tube / DNA bank

Timeline

• Start date: 2018-04-17
• Primary completion: 2022-04-20
• Completion: 2022-04-20
• First posted: 2017-06-15
• Last updated: 2026-03-05

Locations

1 site across 1 country: France