alexa The Relationship of Serum Infliximab Concentrations to Clinical Improvement in Rheumatoid Arthritis
Environmental Sciences

Environmental Sciences

Journal of Biodiversity & Endangered Species

Author(s): E William StClair, Carrie L Wagner, Adedigbo A Fasanmade, Benjamin Wang, Thomas Schaible, Arthur Kavanaugh, Edward C Keystone

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Objective. To investigate the relationship between serum concentrations of infliximab, a monoclonal anti– tumor necrosis factor  antibody, and clinical improve- ment from infliximab therapy for rheumatoid arthritis (RA). Methods. Multiple blood samples were obtained from each of 428 subjects with active RA who were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (ATTRACT [Anti–Tumor Ne- crosis Factor Trial in Rheumatoid Arthritis with Con- comitant Therapy]) evaluating the clinical efficacy and safety of infliximab therapy. Serum levels of infliximab were measured by enzyme-linked immunosorbent assay. Dose-response trends were analyzed using generalized logistic regression techniques. Pharmacokinetic model- ing was used to predict the serum concentrations of infliximab after simulated infusions using doses and dosing intervals not evaluated in the trial. Results. At week 54, 26% of the subjects receiving 3 mg/kg infliximab every 8 weeks had undetectable trough serum levels of infliximab, a significantly greater proportion than in the other 3 treatment groups ( P < 0.001). Increased magnitude of American College of Rheumatology (ACR) response (measured by the ACR-N, a continuous measure of clinical improvement derived from the ACR 20% response criteria) and greater reduction from baseline in serum C-reactive protein level were both associated with higher trough serum concentrations of infliximab ( P < 0.001), as was less progression of radiographic joint damage ( P  0.004), providing support for a dose-response relation- ship. Pharmacokinetic models predicted that decreasing the dosing interval from 8 weeks to 6 weeks would yield higher trough serum levels of infliximab than increasing the dose by 100 mg. Conclusion. These results suggest that some pa- tients with RA may benefit from infliximab given at higher doses than 3 mg/kg or more frequently than every 8 weeks.

This article was published in ARTHRITIS & RHEUMATISM and referenced in Journal of Biodiversity & Endangered Species

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