Clinical trial NCT00840957: Pharmaco Kinetic Variability of Infliximab in Rheumatoid Arthritis
Official title: Pharmaco Kinetic and Pharmacokinetic-Pharmacodynamic Variability of Infliximab
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Rheumatoid Arthritis
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
First posted: 2009-02-11
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Rheumatoid arthritis

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.


Eligibility criteria: 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

Primary outcomes:
measure: Characterizing the PK and PK-PD variability of infliximab in RA
timeFrame: 6 to 12 weeks
Secondary outcomes:
measure: 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
timeFrame: 6 to 12 weeks
Other outcomes:
Locations:
city: Brest
country: France
facility: CHRU de Brest
city: Nantes
country: France
facility: CHRU de Nantes
city: Orléans
country: France
facility: CHR d'Orléans
city: Poitiers
country: France
facility: CHRU de Poitiers
city: Rennes
country: France
facility: CHRU de Rennes
city: Tours
country: France
facility: CHRU de Tours
Study officials:
affiliation: CHRU de Tours
name: Denis MULLEMAN, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ternant D, Ducourau E, Perdriger A, Corondan A, Le Goff B, Devauchelle-Pensec V, Solau-Gervais E, Watier H, Goupille P, Paintaud G, Mulleman D. Relationship between inflammation and infliximab pharmacokinetics in rheumatoid arthritis. Br J Clin Pharmacol. 2014 Jul;78(1):118-28. doi: 10.1111/bcp.12313.