Abstract Background Methotrexate (MTX) is the first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA), yet approximately 30–40% of patients exhibit an inadequate therapeutic response. Early identification of MTX non-responders remains a clinical challenge. Cytokines such as interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), Tumor Necrosis Factor alpha (TNF-alpha), and interleukin-17 (IL-17) are central to RA pathogenesis and may serve as predictive biomarkers of treatment outcomes, therefore, the study aimed to investigate the association of serum levels of IL-6, IL-17, TNF-alpha, and GM-CSF with disease activity and methotrexate response in newly diagnosed, treatment-naïve RA patients. Methods This prospective observational study included 40 newly diagnosed, treatment-naïve RA patients who initiated MTX monotherapy. Serum concentrations of IL-6, IL-17, TNF-α, and GM-CSF were quantified at baseline and after 12 weeks using ELISA. Disease activity was evaluated by the 28-joint Disease Activity Score (DAS28). Patients were stratified into responders and non-responders according to EULAR criteria. Comparative and correlation analyses were conducted to explore the relationship between cytokine profiles and treatment response. Results Baseline serum IL-6 and IL-17 levels were significantly different in MTX non-responders and responders ( p < 0.0172, and 0.0096, respectively), whereas TNF-α and GM-CSF did not differ significantly between groups ( p = 0.6121 and p = 0.1840, respectively). Conclusions Levels of IL-6 and IL17 at onset were significantly higher in the group of patients that did not respond on methotrexate compared to those who did, but their clinical utility as prognostic biomarkers for MTX responsiveness appears limited.
Gvetadze et al. (2026) studied this question.