SAT0091 Clinical remission prediction using baseline gene expression in the peripheral blood of dmard-naÏve rheumatoid arthritis patients treated with methotrexate
Authors: E.V. Tchetina, N.V. Demidova, G.A. Markova
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, which is characterised by erosive arthritis (synovitis) and systemic inflammation. Methotrexate (MTX) is a basic drug for RA treatment. However, presently it is not possible to predict MTX efficacy in every patient while some patients are non-responsive to MTX or the drug may induce adverse effects. Therefore, identification of patients sensitive to MTX before treatment could significantly improve therapy outcome. <h3>Objectives</h3> To investigate the importance of baseline expression of genes involved in the metabolic and energy generation pathways in RA patients, which could serve prognostic biomarkers of treatment response to methotrexate. <h3>Methods</h3> Peripheral blood of 40 DMARD-naïve RA patients aged 47.5±15.5 years old, disease duration 7.9±6.0 weeks treated with MTX (15 mg/week) during two years and 26 healthy age-matched control subjects were examined. Clinical response was assessed by disease activity score (DAS) 28, serum levels of ACPA antibodies, C-reactive protein (CRP), and rheumatoid factor (RF). Clinical remission was assessed according to ACR criteria and DAS28 (DAS28 &lt;2.6). Bone erosion and joint space narrowing (JSN) scores were monitored by X-ray analysis. Protein concentrations were measured using ELISAs. Total RNA was isolated and used in gene expression studies performed with quantitative real-time RT-PCR. <h3>Results</h3> MTX treatment significantly decreased the disease activity according to DAS28. At the end of the study the majority of patients demonstrated moderate disease activity (DAS28 &gt;3.2 &lt;5.1), four patients retained high disease activity while 12, attained remission (DAS28 &lt;2.6). Gene expression analysis has revealed that RA patients, which attained clinical remission after MTX treatment demonstrated significantly higher baseline expression of genes associated with glycolysis (Glut1, PKM), hypoxia (HIF1α), and cell cycle related cyclin D1 compared to other examined RA patients and healthy subjects. RA patients, which retained high disease activity after treatment had baseline expression of genes related to apoptosis (p21, caspase 3), tissue regeneration (TGFβ1, RUNX2) and cyclin D1, significantly lower than that in the controls and other examined RA patients. <h3>Conclusions</h3> Clinical remission attainment in DMARD-naïve RA patients treated with methotrexate is associated with high baseline expression of genes associated with glycolysis, hypoxia and cyclin D1 compared to other examined patients. Non-responsiveness to MTX is accompanied by lower baseline expression of genes related to apoptosis, tissue regeneration, and cyclin D1 compared to controls. Increased baseline expression of cyclin D1 gene compared to healthy subjects could serve a positive prognostic marker of sensitivity to methotrexate therapy. <h3>Acknowledgements</h3> This study was funded by Russian Foundation for Basic Research (project no. 12–04–00038-a to EVT). <h3>Disclosure of Interest</h3> None declared