Long-term evaluation of rheumatoid arthritis activity with erythrocyte methotrexate-polyglutamate 3.

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY Fundamental & Clinical Pharmacology Pub Date : 2025-02-01 DOI:10.1111/fcp.13050
Jean Escal, Marion Poudret, Sophie Hodin, Tiphany Neel, Irina Coman, Hervé Locrelle, Adamah Amouzougan, Thierry Thomas, Xavier Delavenne, Hubert Marotte
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Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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/m2.

Conclusion: Erythrocyte MTX-PG3 concentrations may serve as a marker for RA activity after prolonged treatment. However, BMI could limit their utility as a biomarker.

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红细胞甲氨蝶呤-聚谷氨酸3对类风湿关节炎活动性的长期评价。
背景:甲氨蝶呤(MTX)是类风湿性关节炎(RA)的一线治疗药物,然而30%-50%的RA患者对MTX产生耐药性,这种耐药性可在治疗开始数年后出现。目的:探讨长期接受甲氨蝶呤治疗的RA患者红细胞甲氨蝶呤多谷氨酸(MTX- pg)亚型浓度与临床疾病活动度的关系。方法:在这项横断面研究中,纳入了使用稳定剂量皮下甲氨蝶呤数年的患者。该研究方案已在欧洲药品管理局的临床试验登记处注册(n°2017-004348-39)。患者分为临床缓解组(DAS28 3.2)。采用液相色谱-质谱联用法测定红细胞MTX-PGs浓度。多因素logistic回归分析评估基于MTX-PG3浓度的缓解状态的概率。结果:该研究包括34例活动期RA患者和25例缓解期RA患者。缓解组的中位MTX治疗持续时间为6.4年,而活性组为2.6年(p = 0.001)。与活动期RA患者相比,缓解期患者的中位病程(p = 0.02)更长,体重指数(BMI) (p = 0.03)更低。在BMI为2的患者中,缓解状态与高MTX-PG3浓度呈正相关。结论:红细胞MTX-PG3浓度可作为长期治疗后RA活性的标志。然而,BMI可能会限制它们作为生物标志物的效用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
5.30
自引率
6.90%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.
期刊最新文献
A novel naphthylchalcone ([E]-4-(3-[naphthalen-2-yl]-3-oxoprop-1-en-1-yl) induces intrinsic and extrinsic apoptosis in human acute leukemia cell lines. Body mass index affects imatinib exposure: Real-world evidence from TDM with adaptive dosing. Knockdown of RFC3 enhances the sensitivity of colon cancer cells to oxaliplatin by inducing ferroptosis. Long-term evaluation of rheumatoid arthritis activity with erythrocyte methotrexate-polyglutamate 3. Fluoxetine-induced downregulation of circMap2k1 signaling cascade to improve neurological function after ischemic stroke.
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