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

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.