Association of Pharmacologic Markers of Anti-Tumor Necrosis Factor-α Activity and Etanercept Effectiveness in Juvenile Idiopathic Arthritis.

Therapies targeting tumor necrosis factor-α (TNFα), including etanercept (ETN), have become a mainstay in the treatment of juvenile idiopathic arthritis (JIA). As a result, this work seeks to evaluate the relationship between pharmacologic markers of ETN activity and clinical effectiveness in a cohort of patients with JIA. This is a single-centered, open-label, prospective, cross-sectional study of patients with JIA (n = 26) receiving maintenance ETN. Determination of ETN effectiveness was based on the absence of active arthritis in any joint at the time of sample collection. Patient plasma samples were collected and analyzed for ETN concentrations, anti-ETN antibodies, anti-TNFα activity, and TNFα concentrations. ETN was effective in 46% (n = 12) of patients assessed at the time of sampling. No differences in baseline demographics were observed between patients based on effectiveness. Median [IQR] plasma ETN concentrations were 2094 [1384, 2680] ng/mL. Anti-ETN antibodies were undetectable in all patients. Plasma anti-TNFα activity varied 32-fold and was directly proportionate to plasma ETN concentrations (ρ = 0.75, p = 3.8 × 10-3). Plasma TNFα concentrations were 9-fold higher than previous measurements in patients with JIA not receiving anti-TNFα therapy (p = 3.6 × 10-9). ETN effectiveness was associated with 21% higher ETN concentrations (p = 0.36), 52% higher plasma anti-TNFα activity (p = 0.14), and 84% higher plasma TNFα concentrations (p = 0.008). Among pharmacologic markers of ETN activity measured, plasma TNFα concentrations are most strongly associated with ETN effectiveness in JIA.

Duke Scholars

Author Mara Becker Pediatrics, Rheumatology