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The relationship of serum infliximab concentrations to clinical improvement in rheumatoid arthritis: results from ATTRACT, a multicenter, randomized, double-blind, placebo-controlled trial.

Publication ,  Journal Article
St Clair, EW; Wagner, CL; Fasanmade, AA; Wang, B; Schaible, T; Kavanaugh, A; Keystone, EC
Published in: Arthritis Rheum
June 2002

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.

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Published In

Arthritis Rheum

DOI

ISSN

0004-3591

Publication Date

June 2002

Volume

46

Issue

6

Start / End Page

1451 / 1459

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Radiography
  • Logistic Models
  • Infliximab
  • Humans
  • Double-Blind Method
  • Arthritis, Rheumatoid
  • Arthritis & Rheumatology
  • Antirheumatic Agents
  • Antibodies, Monoclonal
 

Citation

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Chicago
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MLA
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St Clair, E. W., Wagner, C. L., Fasanmade, A. A., Wang, B., Schaible, T., Kavanaugh, A., & Keystone, E. C. (2002). The relationship of serum infliximab concentrations to clinical improvement in rheumatoid arthritis: results from ATTRACT, a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum, 46(6), 1451–1459. https://doi.org/10.1002/art.10302
St Clair, E William, Carrie L. Wagner, Adedigbo A. Fasanmade, Benjamin Wang, Thomas Schaible, Arthur Kavanaugh, and Edward C. Keystone. “The relationship of serum infliximab concentrations to clinical improvement in rheumatoid arthritis: results from ATTRACT, a multicenter, randomized, double-blind, placebo-controlled trial.Arthritis Rheum 46, no. 6 (June 2002): 1451–59. https://doi.org/10.1002/art.10302.
St Clair EW, Wagner CL, Fasanmade AA, Wang B, Schaible T, Kavanaugh A, Keystone EC. The relationship of serum infliximab concentrations to clinical improvement in rheumatoid arthritis: results from ATTRACT, a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002 Jun;46(6):1451–1459.
Journal cover image

Published In

Arthritis Rheum

DOI

ISSN

0004-3591

Publication Date

June 2002

Volume

46

Issue

6

Start / End Page

1451 / 1459

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Radiography
  • Logistic Models
  • Infliximab
  • Humans
  • Double-Blind Method
  • Arthritis, Rheumatoid
  • Arthritis & Rheumatology
  • Antirheumatic Agents
  • Antibodies, Monoclonal