# Efficacy of DMARDs Therapy on the Disease Activity and Gene Expression Levels of FoxO1, FoxO3, Runx1, and Runx3 in Early Rheumatoid Arthritis Patients: A Pre–Post Interventional Study With Healthy Controls

## TL;DR

This study shows that DMARDs treatment reduces inflammation and changes gene activity in early rheumatoid arthritis patients.

## Contribution

The study demonstrates that DMARDs significantly reduce Runx3 gene expression and inflammatory markers in early RA patients.

## Key findings

- DMARDs treatment significantly lowers Runx3 gene expression in early RA patients.
- FoxO1 and FoxO3 gene expression is elevated in RA patients compared to controls.
- IL-6 levels are higher in RA patients before and after treatment than in healthy controls.

## Abstract

Forkhead box O (FoxO) transcription factors exert crucial roles in immune responses. Besides, the Runt‐related transcription factor (Runx) family plays a pivotal role in the development and homeostasis of cartilage and bone. This study assessed the plasma concentrations of the pro‐inflammatory interleukin‐6 (IL‐6) cytokine and the anti‐inflammatory cytokine interleukin‐10 (IL‐10), as well as the gene expression levels of FoxO1, FoxO3, Runx1, and Runx3, in the peripheral blood sample of the early rheumatoid arthritis (RA) patients treated with conventional disease‐modifying antirheumatic drugs (DMARDs) for 6 months relative to normal subjects.

This study examined 30 early DMARDs‐naïve RA patients (before and after treatment) and 30 age‐ and gender‐matched normal individuals. The plasma levels of IL‐6 and IL‐10 were measured by enzyme‐linked immunosorbent assay (ELISA), and the mRNA expression amounts of FoxO1, FoxO3, Runx1, and Runx3 were determined using real‐time PCR.

The plasma IL‐6 concentrations increased significantly in pre‐ and posttreatment RA patients compared with controls (p < 0.001). Moreover, the gene expression of FoxO1 and FoxO3 was enhanced considerably in RA patients (both before and after treatment), compared to controls (p < 0.001 for FoxO1 and p = 0.02 and p = 0.01 for FoxO3, respectively). Runx1 gene expression increased dramatically in pre‐ and posttreatment RA patients compared with the controls (p < 0.001). Runx3 gene expression was meaningfully enhanced in pretreatment RA patients than in normal controls (p < 0.001). Also, DMARDs treatment strikingly reduced Runx3 gene expression levels compared to pretreatment levels (p < 0.001).

DMARDs treatment dramatically diminishes Runx3 gene expression, thereby lowering disease activity and inflammatory markers in the early RA patients.