Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Ohio, and Johns Hopkins University, Baltimore, Maryland.
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Ohio.
Arthritis Care Res (Hoboken). 2024 Dec;76(12):1723-1732. doi: 10.1002/acr.25417. Epub 2024 Sep 17.
We examine levels of candidate blood-based biomarkers (CBBs) in patients with juvenile idiopathic arthritis (JIA) treated with tofacitinib.
Patients with JIA who participated in clinical trial NCT02592434 received tofacitinib from baseline to week 18. Serial serum samples were assayed for CBBs (S100A8/9, S100A12, interleukin-18 [IL-18], serum amyloid A, resistin, vascular endothelial growth factor, angiopoietin-1, angiopoietin-2, matrix metalloproteinase 8 [MMP8], MMP2, tissue inhibitor of metalloproteinases 1, leptin, chemokine [C-X-C motif] ligand 9, soluble IL-2 receptor, intercellular adhesion molecule 1, soluble tumor necrosis factor receptor, IL-6, IL-23, monocyte chemotactic protein 1, chemokine [C-C motif] ligand 18 [CCL18], and CCL20). Association of CBBs with JIA response to treatment from baseline to week 18 were assessed.
This study included 166 patients with polyarticular-course JIA. Paired serum samples from 143 patients were available at both baseline and week 18. Thirty-five percent (50 of 143) of patients had a JIA-American College of Rheumatology 90 (JIA-ACR90) level improvement, whereas 90, 121, and 137 (63%, 85%, and 96%) achieved JIA-ACR70, 50, and 30 improvement at week 18. Despite small numerical differences by JIA category, there were no baseline CBB values that independently predicted a decrease in Juvenile Arthritis Disease Activity Score (JADAS-27) or JIA-ACR90 response by week 18. Decrease in resistin level (baseline to week 18) was significantly associated with week 18 improvement in JADAS-27 and JIA-ACR90 response after adjusting for age, sex, JIA disease duration, and baseline resistin (r 0.79, SE 0.070, P < 0.01, and odds ratio [95% confidence interval] 1.134 [1.018-1.264]). HLA-B27 positivity was significantly associated with not achieving a JIA-ACR90 response at week 18 (P = 0.0097).
Among the CBBs included, only resistin was significantly associated with treatment response, and no CBB was identified that forecasts JIA improvement after initiation of tofacitinib. The association of HLA-B27 positivity with lower response to tofacitinib in JIA is intriguing and merits further study.
我们研究了接受托法替尼治疗的幼年特发性关节炎（JIA）患者候选血液生物标志物（CBB）的水平。
参加临床试验 NCT02592434 的 JIA 患者从基线至第 18 周接受托法替尼治疗。连续采集血清样本以检测 CBB（S100A8/9、S100A12、白细胞介素-18 [IL-18]、血清淀粉样蛋白 A、抵抗素、血管内皮生长因子、血管生成素-1、血管生成素-2、基质金属蛋白酶 8 [MMP8]、MMP2、金属蛋白酶组织抑制剂 1、瘦素、趋化因子 [C-X-C 基序] 配体 9、可溶性白细胞介素 2 受体、细胞间黏附分子 1、可溶性肿瘤坏死因子受体、白细胞介素-6、白细胞介素-23、单核细胞趋化蛋白 1、趋化因子 [C-C 基序] 配体 18 [CCL18] 和 CCL20）。评估从基线到第 18 周 CBB 与 JIA 治疗反应的相关性。
本研究纳入了 166 例多关节型 JIA 患者。143 例患者中有 143 例在基线和第 18 周时均有配对血清样本。35%（50/143）的患者 JIA-美国风湿病学会 90 （JIA-ACR90） 水平改善，而 90、121 和 137（63%、85%和 96%）在第 18 周时分别达到 JIA-ACR70、50 和 30 改善。尽管 JIA 类别存在数值差异，但没有基线 CBB 值可独立预测 Juvenile Arthritis Disease Activity Score（JADAS-27）或 JIA-ACR90 反应在第 18 周下降。抵抗素水平下降（从基线到第 18 周）与 JADAS-27 和 JIA-ACR90 反应在第 18 周的改善显著相关，调整年龄、性别、JIA 疾病持续时间和基线抵抗素后（r 0.79，SE 0.070，P < 0.01，优势比 [95%置信区间] 1.134 [1.018-1.264]）。HLA-B27 阳性与第 18 周未达到 JIA-ACR90 反应显著相关（P = 0.0097）。
在所纳入的 CBB 中，只有抵抗素与治疗反应显著相关，并且没有发现 CBB 可预测托法替尼治疗开始后 JIA 的改善。HLA-B27 阳性与 JIA 对托法替尼的反应较低相关，这很有趣，值得进一步研究。
