Juvenile idiopathic arthritis (JIA) comprises a heterogeneous group of conditions that can cause marked disability and diminished quality of life. Data on predictors of clinical response are insufficient to guide selection of the appropriate biologic agent for individual patients. This study aimed to investigate the propensity of S100A8/9 and S100A12 as predictive biomarkers of abatacept response in polyarticular-course juvenile idiopathic arthritis (pJIA). Data from a phase 3 trial (NCT01844518) of subcutaneous abatacept in patients with active pJIA (n = 219) were used in this exploratory analysis. Association between biomarker levels at baseline and improvements in JIA-American College of Rheumatology (ACR) criteria responses or baseline disease activity (measured by Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein [JADAS27-CRP]) were assessed. Biomarker level changes from baseline to month 4 were assessed for disease outcome prediction up to 21 months. At baseline, 158 patients had available biomarker samples. Lower baseline S100A8/9 levels (≤ 3295 ng/mL) were associated with greater odds of achieving JIA-ACR90 (odds ratio [OR]: 2.54 [95% confidence interval (CI): 1.25–5.18]), JIA-ACR100 (OR: 3.72 [95% CI: 1.48–9.37]), JIA-ACR inactive disease (ID; OR: 4.25 [95% CI: 2.03–8.92]), JADAS27-CRP ID (OR: 2.34 [95% CI: 1.02–5.39]) at month 4, and JIA-ACR ID (OR: 3.01 [95% CI: 1.57–5.78]) at month 16. Lower baseline S100A12 levels (≤ 176 ng/mL) were associated with greater odds of achieving JIA-ACR90 (OR: 2.52 [95% CI: 1.23–5.13]), JIA-ACR100 (OR: 3.68 [95% CI: 1.46–9.28]), JIA-ACR ID (OR: 3.66 [95% CI: 1.76–7.61]), JIA-ACR90 (OR: 2.03 [95% CI: 1.07–3.87]), JIA-ACR100 (OR: 2.14 [95% CI: 1.10–4.17]), and JIA-ACR ID (OR: 4.22 [95% CI: 2.15–8.29]) at month 16. From baseline to month 4, decreases in S100A8/9 and S100A12 generally exceeded 50% among JIA-ACR90/100/ID responders. Lower baseline levels of S100A8/9 and S100A12 proteins predicted better response to abatacept treatment than higher levels and may serve as early predictive biomarkers in pJIA. Decreases in these biomarker levels may also predict longer-term response to abatacept in pJIA.

中文翻译：

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S100 蛋白作为多关节型幼年特发性关节炎阿巴西普反应的潜在预测生物标志物


幼年特发性关节炎 (JIA) 包括一组异质性疾病，可导致明显残疾和生活质量下降。临床反应预测因素的数据不足以指导为个体患者选择合适的生物制剂。本研究旨在调查 S100A8/9 和 S100A12 作为多关节型幼年特发性关节炎 (pJIA) 反应的预测生物标志物的倾向。本探索性分析使用了活动性 pJIA 患者 (n = 219) 皮下注射阿巴西普的 3 期试验 (NCT01844518) 数据。评估了基线生物标志物水平与 JIA-美国风湿病学会 (ACR) 标准反应或基线疾病活动（使用 C 反应蛋白 [JADAS27-CRP] 在 27 个关节中通过幼年关节炎疾病活动评分测量）改善之间的关联。评估从基线到第 4 个月的生物标志物水平变化，以预测长达 21 个月的疾病结果。在基线时，158 名患者拥有可用的生物标志物样本。较低的基线 S100A8/9 水平 (≤ 3295 ng/mL) 与达到 JIA-ACR90 的几率较高相关（比值比 [OR]：2.54 [95% 置信区间 (CI)：1.25–5.18]）、JIA-ACR100（ OR：3.72 [95% CI：1.48–9.37]），JIA-ACR 非活动性疾病（ID；OR：4.25 [95% CI：2.03–8.92]），JADAS27-CRP ID（OR：2.34 [95% CI：1.02） –5.39]) 在第 4 个月，JIA-ACR ID (OR: 3.01 [95% CI: 1.57–5.78]) 在第 16 个月。较低的基线 S100A12 水平 (≤ 176 ng/mL) 与实现 JIA 的可能性更大相关-ACR90（OR：2.52 [95% CI：1.23–5.13]）、JIA-ACR100（OR：3.68 [95% CI：1.46–9.28]）、JIA-ACR ID（OR：3.66 [95% CI：1.76– 7.61]）、JIA-ACR90（OR：2.03 [95% CI：1.07–3.87]）、JIA-ACR100（OR：2.14 [95% CI：1.10–4.17]）和 JIA-ACR ID（OR：4.22 [ 95% CI：2.15–8。29]）在第 16 个月。从基线到第 4 个月，JIA-ACR90/100/ID 应答者中 S100A8/9 和 S100A12 的下降通常超过 50%。较低基线水平的 S100A8/9 和 S100A12 蛋白比较高水平预测对阿巴西普治疗的更好反应，并且可以作为 pJIA 的早期预测生物标志物。这些生物标志物水平的下降也可能预测 pJIA 对阿巴西普的长期反应。