Pharmaco Kinetic Variability of Infliximab in Rheumatoid Arthritis (FAKIR)

Pharmaco Kinetic and Pharmacokinetic-Pharmacodynamic Variability of Infliximab

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Biological: infliximab

• Study Type: Observational
• Enrollment (Actual): 84

Contacts and Locations

Study Locations

• France
  • Brest, France
    • CHRU de Brest
  • Nantes, France
    • CHRU de Nantes
  • Orléans, France
    • CHR d'Orléans
  • Poitiers, France
    • CHRU de POITIERS
  • Rennes, France
    • CHRU de Rennes
  • Tours, France
    • CHRU de TOURS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Rheumatoid arthritis

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
A; Rhumatoid arthritis patient currently receiving infliximab	Biological: infliximab; chimeric monoclonal antibody to Tumor Necrosis Factor-alpha

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Characterizing the PK and PK-PD variability of infliximab in RA	6 to 12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University Hospital, Tours
• Investigators: Principal Investigator: Denis MULLEMAN, MD, CHRU de TOURS

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: February 10, 2009
• First Submitted That Met QC Criteria: February 10, 2009
• First Posted (Estimate): February 11, 2009

Study Record Updates

• Last Update Posted (Estimate): April 9, 2015
• Last Update Submitted That Met QC Criteria: April 8, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Infliximab
• Other Study ID Numbers: PHRI07-DM / FAKIR; 2007-002752-42 (EudraCT Number); 2007-R21 (Other Identifier: CPP); A70582-40 (Other Identifier: AFSSAPS)