血清骨生物标志物水平与类风湿关节炎患者接受阿巴西普治疗反应的相关性：日本多中心、前瞻性、观察性 RA 超声队列研究。
Association between serum bone biomarker levels and therapeutic response to abatacept in patients with rheumatoid arthritis (RA): a multicenter, prospective, and observational RA ultrasound cohort study in Japan.
机构信息
Departments of Community Medicine, Nagasaki University Graduate School of Medical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
Departments of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Medical Sciences, Nagasaki, Japan.
出版信息
BMC Musculoskelet Disord. 2021 Jun 1;22(1):506. doi: 10.1186/s12891-021-04392-5.
BACKGROUND
To evaluate the effect of treatment on serum bone biomarkers and explore whether serum bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept.
METHODS
We enrolled 59 RA patients treated with abatacept from a multicenter, exploratory, short-term, prospective and observational ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) therapy. We evaluated the patients' clinical disease activity and musculoskeletal ultrasound (MSUS) scores. The serum concentrations of five bone biomarkers were evaluated (dickkopf-1 [Dkk-1], sclerostin [SOST], osteocalcin [OC], osteopontin [OPN], and osteoprotegerin [OPG]) by multiplex bead assays at baseline, 3, and 6 months: the change over 6 months was defined as the Δ value. 'Power Doppler (PD) responder' was defined as a patient whose Δtotal PD score over 6 months was greater than the median change.
RESULTS
Abatacept significantly improved the clinical disease activity and MSUS score over 6 months. Serum OPG was significantly elevated at 6 months after the abatacept introduction (p = 0.016). The ΔSOST and ΔOPG were significantly greater in the PD responders versus the non-PD responders (p = 0.0041 and 0.0073, respectively). The serum Dkk-1 at baseline was significantly lower in the PD responders (n = 30) vs. the non-PD responders (n = 29) (p = 0.026). A multivariate logistic regression analysis showed that the serum Dkk-1 at baseline (odds ratio 0.50, 95% confidence interval [CI] 0.23-0.91, p = 0.043) was an independent predictor of PD responder status.
CONCLUSION
Serum levels of bone biomarkers may be useful for predicting RA patients' therapeutic responses to abatacept.
TRIAL REGISTRATION
Name of the registry: Assessment of therapeutic responsiveness by imaging of the joints in patients with rheumatoid arthritis; A observational cohort study Trial registration number: UMIN000012524 Date of registration: 12/9/2013 URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000014657.
背景
评估治疗对血清骨生物标志物的影响，并探讨血清骨生物标志物是否与接受阿巴西普治疗的类风湿关节炎（RA）患者的治疗反应相关。
方法
我们从一项多中心、探索性、短期、前瞻性和观察性超声队列研究中招募了 59 名接受阿巴西普治疗的 RA 患者，这些患者接受了生物制剂或靶向合成疾病修饰抗风湿药物（DMARD）治疗。我们评估了患者的临床疾病活动度和肌肉骨骼超声（MSUS）评分。基线、3 个月和 6 个月时通过多重珠粒测定法评估了 5 种骨生物标志物（Dickkopf-1 [Dkk-1]、骨硬化素 [SOST]、骨钙素 [OC]、骨桥蛋白 [OPN]和护骨素 [OPG]）的血清浓度：6 个月的变化定义为Δ值。“功率多普勒（PD）应答者”定义为 6 个月时总 PD 评分的Δ值大于中位数变化的患者。
结果
阿巴西普在 6 个月内显著改善了临床疾病活动度和 MSUS 评分。阿巴西普引入后 6 个月时血清 OPG 显著升高（p=0.016）。PD 应答者的ΔSOST 和 ΔOPG 明显大于非 PD 应答者（p=0.0041 和 0.0073）。PD 应答者（n=30）的基线血清 Dkk-1 明显低于非 PD 应答者（n=29）（p=0.026）。多变量逻辑回归分析显示，基线血清 Dkk-1（优势比 0.50，95%置信区间[CI]0.23-0.91，p=0.043）是 PD 应答者状态的独立预测因子。
结论
血清骨生物标志物水平可能有助于预测 RA 患者对阿巴西普治疗的反应。
试验注册
关节影像学评估类风湿关节炎患者治疗反应的名称；A 观察性队列研究 试验注册编号：UMIN000012524 注册日期：2013 年 12 月 9 日 试验注册网址：https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000014657.
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