Gene Expression Profiling in PBMCs as a Tool for Prediction of Infliximab Responsiveness in Rheumatoid Arthritis
|ClinicalTrials.gov Identifier: NCT00213564|
Recruitment Status : Completed
First Posted : September 21, 2005
Last Update Posted : June 26, 2013
The objective of the study is to identify and validate predictive markers of infliximab responsiveness in RA patients by 2 approaches: i) measuring biochemical, immunological and bone markers in sera because of their involvement in pathogenic mechanisms; ii) identifying gene-expression signatures in PBMCs by the transcriptomic analysis.
Patients with active RA (ACR criteria) were given i.v. 3 mg/kg infliximab associated with metotrexate at weeks 0, 2, 6, and every 8th week. Infliximab efficacy was evaluated at week 14, using the EULAR response criteria.
- Just before the starting of infliximab treatment, the following parameters were measured in the sera: i) immunological tests: rheumatoid factor (IgA, IgG, IgM), anti-CCP, autoAb recognizing the 27 C-terminal fragment (ACAST-C27) and domain I (ACAST-DI) of calpastatin, anti-G6PI, anti a-enolase, anti-keratin and anti-perinuclear factor; ii) biochemical markers: CRP, MMP-1, MMP-3, TIMP-1, TIMP-2; markers of bone resorption: pyridinolin, deoxypyridinolin, osteoprotegerin, sRANKL, COMP. The predictive value of each parameter for a response/non-response to infliximab was analysed using Fischer's exact, Mann-Whitney and Chi2 tests.
- A blood sample was collected just before the onset of infliximab treatment and total RNAs were extracted from the peripheral blood mononuclear cells. The [33P] radiolabeled mRNAs were hybridized (duplicate or triplicate) over a set of 10.000 human cDNA probes spotted at a high density on nylon membranes. Data were normalized and filtered to allow the comparison between RNA samples. Statistical analyses were performed with the R software and hierarchical clustering was performed with the Cluster and Tree View softwares.
|Condition or disease||Intervention/treatment||Phase|
|Rheumatoid Arthritis||Drug: response to infliximab associated with methotrexate||Phase 4|
|Study Type :||Observational|
|Estimated Enrollment :||40 participants|
|Official Title:||Gene Expression Profiling in PBMCs as a Tool for Prediction of Infliximab Responsiveness in Rheumatoid Arthritis|
|Study Start Date :||April 2003|
|Primary Completion Date :||May 2004|
|Study Completion Date :||December 2005|
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00213564
|CHU de Rouen - Hôpitaux de Rouen|
|Rouen, France, 76031|
|Principal Investigator:||Xavier Le Loët||Rouen university Hospital|