D.T. and D.M. contributed equally to this work.
Influence of methotrexate on infliximab pharmacokinetics and pharmacodynamics in ankylosing spondylitis
Article first published online: 8 DEC 2011
© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 73, Issue 1, pages 55–65, January 2012
How to Cite
Ternant, D., Mulleman, D., Lauféron, F., Vignault, C., Ducourau, E., Wendling, D., Goupille, P. and Paintaud, G. (2012), Influence of methotrexate on infliximab pharmacokinetics and pharmacodynamics in ankylosing spondylitis. British Journal of Clinical Pharmacology, 73: 55–65. doi: 10.1111/j.1365-2125.2011.04050.x
- Issue published online: 8 DEC 2011
- Article first published online: 8 DEC 2011
- Accepted manuscript online: 22 JUN 2011 03:52AM EST
- Received; 8 October 2010; Accepted; 10 June 2011; Accepted Article; 22 June 2011
- ankylosing spondylitis;
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Infliximab pharmacokinetics in ankylosing spondylitis has been described but using sparce data.
• A previous work suggests that infliximab concentrations influence clinical response in ankylosing spondylitis, but the infliximab concentration–effect relationship is not known in this disease.
• Methotrexate was shown to influence infliximab pharmacokinetics in rheumatoid arthritis.
WHAT THIS STUDY ADDS
• This study is the first to describe infliximab pharmacokinetics in ankylosing arthritis using rich data.
• The infliximab concentration explains only a small part of interindividual variability in the response of ankylosing arthritis patients.
• Contrary to what is observed in rheumatoid arthritis, methotrexate influences neither infliximab pharmacokinetics nor concentration–response relationship in ankylosing spondylitis.
Infliximab, an anti-tumour necrosis factor α monoclonal antibody, has profoundly modified the treatment of several inflammatory diseases. The objective was to assess the influence of methotrexate on the variability of infliximab pharmacokinetics and concentration–effect relationship in axial ankylosing spondylitis (AAS) patients.
Twenty-six patients with AAS were included in a prospective study. They were treated by infliximab 5 mg kg−1 infusions at weeks 0, 2, 6, 12 and 18. Infliximab concentrations were measured before, and 2 and 4 h after each infusion, and at each intermediate visit (weeks 1, 3, 4, 5, 8, 10 and 14). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was measured at each visit. Infliximab pharmacokinetics was described using a two-compartment model with first-order distribution and elimination constants. A population approach was used. Infliximab pharmacodynamics was described using the area under the BASDAI curve.
A total of 507 blood samples and 329 BASDAI measurements were collected. The following pharmacokinetic parameters were obtained (interindividual coefficient of variation): volumes of distribution for the central compartment = 2.4 l (9.6%) and peripheral compartment = 1.8 l (26%), systemic clearance = 0.23 l day−1 (22%) and intercompartment clearance = 2.3 l day−1. Methotrexate influenced neither pharmacokinetic nor BASDAI variability.
Using the present dosage, the clinical efficacy of infliximab is only weakly influenced by its serum concentrations. The results do not support the combination of methotrexate with infliximab in ankylosing spondylitis.