Pharmaco Kinetic Variability of Infliximab in Rheumatoid Arthritis

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Biological: infliximab

• Registration Number: NCT00840957
• Lead Sponsor: University Hospital, Tours

Brief Summary

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:

1. to characterize the PK and PK-PD variability of infliximab in RA, using clinical criteria and biomarkers, assessed over time ;

2. 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-11
• Study First Submitted: 2009-02-10
• Study First Submitted QC: 2009-02-10
• Study First Posted: 2009-02-11
• Primary Completion: 2009-11
• Study Completion: 2009-11
• Status Verified: 2015-04
• Last Update Submitted: 2015-04-08
• Last Update Posted: 2015-04-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 84

Inclusion Criteria

• Rheumatoid arthritis according to ACR criteria
• Patient already receiving infliximab for more than 14 weeks
• No modification of the dose regimen of infliximab since the last infusion
• No modification of disease modifying anti rheumatic drugs since the last 4 weeks

Exclusion Criteria

• Surgery scheduled during the duration of the study
• Pregnancy
• infection, malignancy, immune reaction to infliximab or demyelinating diseases

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
A	infliximab	Rhumatoid arthritis patient currently receiving infliximab

Primary Outcome Measures

Name	Time	Method
Characterizing the PK and PK-PD variability of infliximab in RA	6 to 12 weeks

Secondary Outcome Measures

Name	Time	Method
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	6 to 12 weeks

Trial Locations

Locations (6)

CHR d'Orléans; 🇫🇷 Orléans, France

CHRU de Rennes; 🇫🇷 Rennes, France

CHRU de Brest; 🇫🇷 Brest, France

CHRU de Nantes; 🇫🇷 Nantes, France

CHRU de Poitiers; 🇫🇷 Poitiers, France

CHRU de Tours; 🇫🇷 Tours, France