Escudero Alejandro, Alperi Mercedes, Turrion Ana Isabel, Lopez Rosario, Yebra Tatiana, Cordero Gema, Diez Teresa, Portero Isabel, Blanco Francisco J
Hospital Universitario Reina Sofia, Universidad de Cordoba, Cordoba, Spain.
IMIBIC Group GC05-Chronic systemic-inflammatory autoimmune diseases of the musculoskeletal system and connective tissue, Cordoba, Spain.
PLoS One. 2025 Aug 6;20(8):e0329440. doi: 10.1371/journal.pone.0329440. eCollection 2025.
International guidelines recommend methotrexate (MTX) as the first-choice treatment in rheumatoid arthritis (RA). Although most patients with recently diagnosed arthritis achieve low disease activity or remission with MTX, about 30-40% do not significantly decrease disease activity after 6-month treatment. Predicting response is essential for choosing the best therapeutic option during the window of opportunity.
This study aimed to evaluate the performance of two new tests measuring the in vitro response to MTX in MTX-naive patients with RA and the association of the test results with clinical remission after 6-month treatment with MTX.
This prospective 6-month study was conducted on 31 RA patients starting MTX treatment. Monocyte metabolic activity (Monocytes Test) and reactive oxygen species (ROS Test) in peripheral blood were measured in vitro before treatment, and response to MTX and remission was measured at 6 months. The area under the receiver operating characteristic curve (AUC) for predicting 6-month remission was calculated with 95% confidence intervals (CI) for each test.
Patients in remission (71%) and not in remission (29%) at 6 months showed no statistically significant clinical differences at baseline. They only differed in test results: ROS levels were higher in patients who achieved 6-month remission than in those who did not (p < 0.001), and monocyte levels were lower in patients who achieved remission than in those who did not (p < 0.05). Prediction accuracy was high, with AUC values of 0.919 (95% CI [0.813-1.025]) and 0.826 (95% CI [0.664-0.989]), respectively, for ROS and monocyte levels.
In MTX-naive patients with RA, the pharmacological response to MTX can be adequately predicted in vitro by quantifying ROS production and total monocytes from peripheral blood mononuclear cells.
国际指南推荐甲氨蝶呤（MTX）作为类风湿关节炎（RA）的首选治疗药物。尽管大多数新诊断的关节炎患者使用MTX后可实现低疾病活动度或缓解，但约30%-40%的患者在6个月治疗后疾病活动度未显著降低。在机会窗口期预测反应对于选择最佳治疗方案至关重要。
本研究旨在评估两种新测试在未使用过MTX的RA患者中测量体外对MTX反应的性能，以及测试结果与MTX治疗6个月后临床缓解的相关性。
本前瞻性6个月研究对31例开始MTX治疗的RA患者进行。治疗前体外测量外周血中的单核细胞代谢活性（单核细胞测试）和活性氧（ROS测试），并在6个月时测量对MTX的反应和缓解情况。计算每个测试预测6个月缓解的受试者工作特征曲线下面积（AUC）及95%置信区间（CI）。
6个月时缓解的患者（71%）和未缓解的患者（29%）在基线时无统计学显著的临床差异。他们仅在测试结果上存在差异：达到6个月缓解的患者ROS水平高于未缓解的患者（p<0.001），且缓解患者的单核细胞水平低于未缓解患者（p<0.05）。预测准确性较高，ROS和单核细胞水平的AUC值分别为0.919（95%CI[0.813-1.025]）和0.826（95%CI[0.664-0.989]）。
在未使用过MTX的RA患者中，通过对外周血单个核细胞中ROS产生和总单核细胞进行定量，可在体外充分预测对MTX的药理反应。
