研究动态
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作用享替那普(Etanercept)和阿达木单抗(Adalimumab)对风湿性关节炎女性患者血清软骨重塑标志物水平的影响。

Effects of Etanercept and Adalimumab on Serum Levels of Cartilage Remodeling Markers in Women with Rheumatoid Arthritis.

发表日期:2023 Aug 09
作者: Anna Szeremeta, Agnieszka Jura-Półtorak, Aleksandra Zoń-Giebel, Krystyna Olczyk, Katarzyna Komosińska-Vassev
来源: Arthritis & Rheumatology

摘要:

肿瘤坏死因子 α 抑制剂 (TNFαI) 治疗与显著抑制影像进展有关,从而改善类风湿性关节炎 (RA) 患者的身体功能和生活质量。TNFαI 阻止关节破坏的机制尚不清楚。本研究评估了15个月的联合甲氨蝶呤抗TNF-α治疗对女性 RA 患者循环软骨代谢标志物水平的影响。应用免疫测定方法,在 TNFαI治疗开始后的基线和15个月时评估了胶原 II 类C-末端剪切新表位 (C2C)、C-末端前蛋白 II 类胶原肽 (PIICP)、软骨寡聚体基质蛋白 (COMP) 和基质金属蛋白酶-3 (MMP-3) 的血清水平。与健康受试者相比,RA女性患者的基线 COMP、C2C 和 MMP-3 水平及 C2C/PIICP 比值显著增高。RA患者与对照组之间的 PIICP 水平没有差异。TNFαI治疗15个月后,C2C、COMP 和 MMP-3 的血清水平下降,而 PIICP 水平增加,但仍未与对照组有差异。这些变化伴随着显著降低的 C2C/PIICP 比值。在开始 TNFαI 治疗之前,血清 COMP 水平与患者的年龄 (p < 0.05) 和基于红细胞沉降率的28个关节疾病活动评分值 (DAS28-ESR; p < 0.05) 显著相关。此外,多元线性回归分析显示,在模型调整后,基线 COMP 水平与 DAS28-ESR 值保持显着关联 (β = 287.74, p = 0.022, R2模型 = 0.25)。C2C/PIICP 比值获得了最大的受试者工作特征曲线下面积 (AUC: 0.830, 95% CI: 0.727-0.932, p < 0.001)。我们的结果表明,长期联合使用抗TNF-α治疗和 MTX 对软骨重塑具有益处,与 RA 患者的临床改善相关。C2C/PIICP 比值可以帮助监测 RA 患者抗TNF-α治疗的有效性。
Tumor necrosis factor α inhibitor (TNFαI) therapy is associated with a significant inhibition of radiographic progression, resulting in improved physical function and quality of life among patients with rheumatoid arthritis (RA). The mechanism by which TNFαI prevent joint destruction is still unknown. In this study, the effect of 15-month anti-TNF-α therapy in combination with methotrexate on circulating levels of biochemical markers of cartilage turnover in female RA patients was assessed. Serum levels of collagen type II C-terminal cleavage neoepitope (C2C), C-terminal propeptide of type II collagen (PIICP), cartilage oligomeric matrix protein (COMP), and matrix metalloproteinase-3 (MMP-3) were evaluated using immunoassays at baseline and 15 months after the start of TNFαI treatment. Baseline COMP, C2C, and MMP-3 levels and C2C/PIICP ratios were significantly higher in women with RA compared with those observed in the healthy subjects. No differences in PIICP levels between the controls and the women with RA were observed. After 15 months of TNFαI treatment, serum levels of C2C, COMP, and MMP-3 decreased, whereas the levels of PIICP increased but were still not different from those of the controls. These changes were accompanied by significantly reduced C2C/PIICP ratios. Before the start of TNFαI therapy, serum levels of COMP significantly correlated with the patients' ages (p < 0.05) and their 28-joint disease activity score values based on their erythrocyte sedimentation rates (DAS28-ESR; p < 0.05). Moreover, multiple linear regression analysis showed that baseline COMP levels retained a significant association with DAS28-ESR value (β = 287.74, p = 0.022, R2 model = 0.25) after model adjustments. The largest area under the ROC curve was obtained for C2C/PIICP ratios (AUC: 0.830, 95% CI: 0.727-0.932, p < 0.001). Our results suggest that long-term anti-TNF-α therapy combined with MTX has a beneficial effect on cartilage remodeling that is associated with clinical improvement among RA patients. Serum C2C/PIICP ratios may help to monitor the effectiveness of anti-TNF-α treatment among RA patients.