Escal Jean, Poudret Marion, Hodin Sophie, Neel Tiphany, Coman Irina, Locrelle Hervé, Amouzougan Adamah, Thomas Thierry, Delavenne Xavier, Marotte Hubert
CHU Saint-Etienne, Laboratoire de Pharmacologie et Toxicologie, Mines Saint-Etienne, INSERM, SAINBIOSE U1059, Université Jean Monnet Saint-Étienne, Saint-Etienne, France.
CHU Saint-Étienne, Service de Rhumatologie, Saint-Etienne, France.
Fundam Clin Pharmacol. 2025 Feb;39(1):e13050. doi: 10.1111/fcp.13050.
Methotrexate (MTX) is the first-line treatment for Rheumatoid Arthritis (RA), yet 30%-50% of RA patients develop resistance to MTX, which can manifest several years after treatment initiation.
This study investigates the relationship between erythrocyte methotrexate polyglutamates (MTX-PGs) subtype concentrations and clinical disease activity in RA patients undergoing long-term MTX treatment.
In this cross-sectional study, patients on a stable dose of subcutaneous MTX for several years were included. The study protocol was registered in the European Medicines Agency's clinical trials register (n°2017-004348-39). Patients were classified as either in clinical remission (DAS28 <2.6) or having active disease (DAS28 >3.2). Erythrocyte MTX-PGs concentrations were measured using liquid chromatography coupled with mass spectrometry. Multivariate logistic regression analysis assessed the probability of remission status based on MTX-PG3 concentrations.
The study included 34 patients with active RA and 25 in remission. The remission group had a median MTX treatment duration of 6.4 years compared to 2.6 years for the active group (p = 0.001). Patients in remission had a longer median disease duration (p = 0.02) and a lower Body Mass Index (BMI) (p = 0.03) than those with active RA. A positive correlation was found between remission status and high MTX-PG3 concentrations in patients with a BMI <25 kg/m.
Erythrocyte MTX-PG3 concentrations may serve as a marker for RA activity after prolonged treatment. However, BMI could limit their utility as a biomarker.
甲氨蝶呤（MTX）是类风湿关节炎（RA）的一线治疗药物，但30%-50%的RA患者会对MTX产生耐药性，这种耐药性可能在治疗开始数年后出现。
本研究调查长期接受MTX治疗的RA患者红细胞甲氨蝶呤多聚谷氨酸盐（MTX-PGs）亚型浓度与临床疾病活动度之间的关系。
在这项横断面研究中，纳入了数年来皮下注射MTX剂量稳定的患者。该研究方案已在欧洲药品管理局的临床试验注册库中注册（编号：2017-004348-39）。患者被分类为临床缓解（疾病活动度评分28关节（DAS28）<2.6）或疾病活动（DAS28>3.2）。使用液相色谱-质谱联用仪测量红细胞MTX-PGs浓度。多因素逻辑回归分析基于MTX-PG3浓度评估缓解状态的概率。
该研究纳入了34例疾病活动的RA患者和25例缓解患者。缓解组MTX治疗的中位持续时间为6.4年，而疾病活动组为2.6年（p=0.001）。与疾病活动的RA患者相比，缓解患者的疾病持续时间中位数更长（p=0.02），体重指数（BMI）更低（p=0.03）。在BMI<25kg/m²的患者中，缓解状态与高MTX-PG3浓度之间存在正相关。
长期治疗后，红细胞MTX-PG3浓度可能作为RA活动度的一个标志物。然而，BMI可能会限制其作为生物标志物的效用。
