The relationship of serum Remicade concentrations to clinical improvement in RA: Results from ATTRACT

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Arthritis Rheum 2002 Jun;46(6):1451-9

The relationship of serum infliximab concentrations to clinical

improvement in rheumatoid arthritis: Results from ATTRACT, a

multicenter, randomized, double-blind, placebo-controlled trial.

St Clair EW, Wagner CL, Fasanmade AA, Wang B, Schaible T, Kavanaugh A,

Keystone EC.

Duke University Medical Center, Durham, North Carolina.

Objective: To investigate the relationship between serum concentrations

of infliximab, a monoclonal anti-tumor necrosis factor alpha antibody,

and clinical improvement 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

Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant 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 modeling 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 relationship.

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 patients with RA may benefit

from infliximab given at higher doses than 3 mg/kg or more frequently

than every 8 weeks.

PMID: 12115174