Pharmaco Kinetic Variability of Infliximab in Rheumatoid Arthritis (FAKIR)
Infliximab is a chimeric monoclonal antibody directed towards Tumor Necrosis Factor -alpha that is largely used in inflammatory diseases such as rheumatoid arthritis (RA).
A relationship between dose and clinical outcomes was shown in populations of RA patients but there is an interindividual variability of this relationship. At an individual level, this dose-effet relationship can be separated into the dose-concentration (pharmacokinetic or PK) and the concentration-effet (pharmacokinetic-pharmacodynamic or PK-PD) relationships.
Serum trough concentrations of infliximab have been shown to be variable between patients receiving the same treatment regimen. This PK variability may be explained by several factors (e.g. genetic and immunological factors). The concentration-effect relationship may also be variable and the sources of this variability need to be studied as well. To date no detailed infliximab PK analysis has been published. The sources of variability of the dose-effect relationship need to be characterized to optimize infliximab dosing regimen in patients.
The FAKIR study is a multicenter prospective observational study that will focus on patients treated with infliximab. Its aims are:
- to characterize the PK and PK-PD variability of infliximab in RA, using clinical criteria and biomarkers, assessed over time ;
- to study the influence of the polymorphism of FCGRT (the gene encoding FcRn) on the PK variability of infliximab; to study the influence of the polymorphism of FCGR3A (the gene encoding Fc gamma RIIIa) on the PK-PD variability of infliximab; and to study the influence of antibodies toward infliximab on the PK and PK-PD variabilities of infliximab.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Pharmaco Kinetic and Pharmacokinetic-Pharmacodynamic Variability of Infliximab|
- Characterizing the PK and PK-PD variability of infliximab in RA [ Time Frame: 6 to 12 weeks ] [ Designated as safety issue: No ]
- Studying the relation between FCGRT polymorphism and the PK variability of infliximab; the relation between FCGR3A polymorphism and the PK-PD variability of infliximab; and the relation between ATI and the PK and PK-PD variabilities of infliximab [ Time Frame: 6 to 12 weeks ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
whole blood and serum
|Study Start Date:||November 2007|
|Study Completion Date:||November 2009|
|Primary Completion Date:||November 2009 (Final data collection date for primary outcome measure)|
Rhumatoid arthritis patient currently receiving infliximab
chimeric monoclonal antibody to Tumor Necrosis Factor-alpha
Please refer to this study by its ClinicalTrials.gov identifier: NCT00840957
|CHRU de Brest|
|CHRU de Nantes|
|CHRU de Poitiers|
|CHRU de Rennes|
|CHRU de Tours|
|Principal Investigator:||Denis MULLEMAN, MD||CHRU de Tours|