在 ESPOIR 队列中验证维生素 K 依赖性蛋白 S（PROS）作为一种潜在的生物标志物，能够预测对甲氨蝶呤/依那西普联合治疗的反应。
Validation in the ESPOIR cohort of vitamin K-dependent protein S (PROS) as a potential biomarker capable of predicting response to the methotrexate/etanercept combination.
机构信息
Rouen University Hospital, Department of Rheumatology & CIC-CRB1404, Normandie Univ, UNIROUEN, F 76000, Rouen, France.
Inserm 1234 (PANTHER), F76000, Rouen, France.
出版信息
Arthritis Res Ther. 2022 Mar 21;24(1):72. doi: 10.1186/s13075-022-02762-5.
BACKGROUND
To validate the ability of PROS (vitamin K-dependent protein S) and CO7 (complement component C7) to predict response to the methotrexate (MTX)/etanercept (ETA) combination in rheumatoid arthritis (RA) patients who received this therapeutic combination in a well-documented cohort.
METHOD
From the ESPOIR cohort, RA patients having received the MTX/ETA or MTX/adalimumab (ADA) combination as a first-line biologic treatment were included. Serum concentrations of PROS and CO7 were measured by ELISA prior to the initiation of ETA or ADA, at a time where the disease was active (DAS28 ESR > 3.2). The clinical efficacy (response/non-response) of both combinations has been evaluated after at least 6 months of treatment, according to the EULAR response criteria with some modifications.
RESULTS
Thirty-two were treated by MTX/ETA; the numbers of responders and non-responders were 24 and 8, respectively. Thirty-three patients received the MTX/ADA combination; 27 and 5 patients were respectively responders and non-responders. While there were no differences for demographic, clinical, biological, and X-rays data, as well as for CO7, serum levels of PROS tended to be significantly higher in responders to the MTX/ETA combination (p = 0.08) while no difference was observed in the group receiving MTX/ADA. For PROS, the best concentration threshold to differentiate both groups was calculated at 40 μg/ml using ROC curve. The theranostic performances of PROS appeared better for the ETA/MTX combination. When considering the response to this combination, analysis of pooled data from ESPOIR and SATRAPE (initially used to validate PROS and CO7 as potential theranostic biomarkers) cohorts led to a higher theranostic value of PROS that became significant (p = 0.009).
CONCLUSION
PROS might be one candidate of a combination of biomarkers capable of predicting the response to MTX/ETA combination in RA patients refractory to MTX.
TRIAL REGISTRATION
ClinicalTrials.gov identifiers: NCT03666091 and NCT00234234 .
背景
在一项有充分记录的队列研究中，我们验证了蛋白 S（维生素 K 依赖性蛋白 S，PROS）和 C7 补体（补体成分 C7，CO7）在接受甲氨蝶呤（MTX）/依那西普（ETA）联合治疗的类风湿关节炎（RA）患者中预测该联合治疗应答的能力。
方法
从 ESPOIR 队列中纳入了接受 MTX/ETA 或 MTX/阿达木单抗（ADA）联合作为一线生物治疗的 RA 患者。在开始使用 ETA 或 ADA 之前，通过 ELISA 测量 PROS 和 CO7 的血清浓度，此时疾病处于活动期（DAS28 ESR>3.2）。根据 EULAR 缓解标准，对两种联合治疗的临床疗效（缓解/非缓解）进行了评估，其中一些标准进行了修改。
结果
32 例患者接受 MTX/ETA 治疗；缓解者和非缓解者分别为 24 例和 8 例。33 例患者接受 MTX/ADA 联合治疗；缓解者和非缓解者分别为 27 例和 5 例。虽然在人口统计学、临床、生物学和 X 射线数据以及 CO7 方面没有差异，但在 MTX/ETA 联合治疗的缓解者中，PROS 的血清水平倾向于显著更高（p=0.08），而在接受 MTX/ADA 治疗的患者中则没有差异。对于 PROS，使用 ROC 曲线计算出区分两组的最佳浓度阈值为 40μg/ml。PROS 对 ETA/MTX 联合治疗的诊断性能似乎更好。当考虑到对该联合治疗的反应时，对 ESPOIR 和 SATRAPE（最初用于验证 PROS 和 CO7 作为潜在诊断生物标志物）队列数据的汇总分析导致 PROS 的诊断性能更高，且具有统计学意义（p=0.009）。
结论
PROS 可能是预测对 MTX 耐药的 RA 患者 MTX/ETA 联合治疗应答的生物标志物组合之一。
试验注册
ClinicalTrials.gov 标识符：NCT03666091 和 NCT00234234。
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