Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Methotrexate Does Not Influence Infliximab Pharmacokinetics and Concentration-Effect Relationship in Ankylosing Spondylitis.
Ducourau2, Emilie, Ternant2, David, Lauferon2, Francine, Mulleman2, Denis, Wendling1, Daniel, Paintaud2, Gilles, Goupille2, Philippe
Methotrexate (MTX) was shown to modify IFX pharmacokinetics in rheumatoid arthritis (1). However, its combination with infliximab in the treatment of ankylosing spondylitis (AS) is not recommended. The objective of this study was to investigate the influence of MTX on IFX pharmacokinetics and pharmacokinetic-pharmacodynamics (PK-PD) in axial AS patients.
Patients with axial AS were randomized to receive infliximab alone (infusions of 5 mg/kg at week 0, 2, 6, 12 and 18) or infliximab combined with MTX (10 mg/week). A clinical and laboratory evaluation was performed at each visit. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was the primary endpoint of clinical response. The pharmacokinetics of IFX was described using a two-compartment model with first order distribution and elimination constants. The relationship between IFX concentration and BASDAI score was described using an indirect response model with inhibition of BASDAI 'input'. A population approach was used and models were run simultaneously. The influence of MTX was tested as a covariate on each pharmacokinetic and PK-PD parameter.
Twenty six patients were included (14 with MTX, 12 without MTX). A total of 507 blood samples were available for measurement of serum infliximab (2). The PK analysis showed an influence of body size and history of a previous anti-TNF failure on the distribution volume of the central compartment but did not identify any influence of MTX on the estimated parameters (3). The evolution of BASDAI, clinical measurements and biomarkers of inflammation were no different in both groups. Main pharmacodynamic parameters were the maximum inhibition of BASDAI input (Em) = 46%, (59%) and the concentration leading to 50% of Em (C50) = 6.3 mg/L. MTX did not influence any of pharmacokinetic or PK-PD parameters.
MTX influenced neither pharmacokinetics nor PK-PD of IFX. Our study does not support the combination of methotrexate with infliximab in axial AS.
clinicaltrials.gov as NCT00507403
To cite this abstract, please use the following information:
Ducourau, Emilie, Ternant, David, Lauferon, Francine, Mulleman, Denis, Wendling, Daniel, Paintaud, Gilles, et al; Methotrexate Does Not Influence Infliximab Pharmacokinetics and Concentration-Effect Relationship in Ankylosing Spondylitis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1945