Arain Mudassar I, Polireddy Kishore, Fricovsky Eduardo S, Becker Mara L, Kazi Mohsin, Funk Ryan S
Clinical Research Program, College of Health and Human Services, University of North Carolina, Wilmington, Wilmington, North Carolina, USA.
Pharmacy Practice, School of Pharmacy, University of Kansas, Lawrence, Kansas, USA.
Pharmacol Res Perspect. 2025 Oct;13(5):e70166. doi: 10.1002/prp2.70166.
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). Plasma TNFα concentrations were 9-fold higher than previous measurements in patients with JIA not receiving anti-TNFα therapy (p = 3.6 × 10). 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.
包括依那西普（ETN）在内的靶向肿瘤坏死因子-α（TNFα）的疗法已成为青少年特发性关节炎（JIA）治疗的主要手段。因此，本研究旨在评估一组JIA患者中ETN活性的药理学标志物与临床疗效之间的关系。这是一项针对接受ETN维持治疗的JIA患者（n = 26）的单中心、开放标签、前瞻性横断面研究。ETN疗效的判定基于样本采集时任何关节均无活动性关节炎。收集患者血浆样本并分析ETN浓度、抗ETN抗体、抗TNFα活性和TNFα浓度。在采样时评估的患者中，46%（n = 12）的患者ETN治疗有效。根据疗效，患者之间的基线人口统计学特征未观察到差异。血浆ETN浓度中位数[四分位间距]为2094[1384, 2680] ng/mL。所有患者均未检测到抗ETN抗体。血浆抗TNFα活性变化32倍，且与血浆ETN浓度直接成正比（ρ = 0.75，p = 3.8×10）。血浆TNFα浓度比未接受抗TNFα治疗的JIA患者先前的测量值高9倍（p = 3.6×10）。ETN疗效与ETN浓度高21%（p = 0.36）、血浆抗TNFα活性高52%（p = 0.14）和血浆TNFα浓度高84%（p = 0.008）相关。在所测量的ETN活性药理学标志物中，血浆TNFα浓度与JIA中ETN疗效的相关性最强。
