THERAPEUTIC MODULATION OF MIR-155 IN EARLY RHEUMATOID ARTHRITIS

Background: Rheumatoid arthritis (RA) is a progressive autoimmune disease marked by synovial inflammation and joint destruction. MicroRNA-155 (miR-155) plays a key role in immune regulation and inflammation, with overexpression linked to RA pathogenesis. Targeting miR-155 offers a novel approach to modulate immune responses at the molecular level, particularly in early disease phases when intervention can prevent long-term damage. Objective: This randomized controlled trial evaluated the clinical efficacy of targeted miR-155 inhibition therapy combined with physical therapy in patients with early rheumatoid arthritis over a 12-week period. Methods: Sixty patients with early RA were randomized equally into two groups: one receiving intra-articular miR-155 antisense oligonucleotide therapy alongside structured physical therapy, and the other receiving physical therapy alone. Primary outcomes included changes in inflammatory biomarkers (CRP, IL-6, TNF-α), and secondary outcomes assessed disease activity (DAS28), physical function (HAQ-DI, TUG test), and pain/stiffness via visual analog scales. Data were analyzed using independent t-tests and repeated measures ANOVA. Results: The intervention group showed significant reductions in CRP (16.5 to 7.9 mg/L), IL-6 (42.8 to 21.6 pg/mL), and TNF-α (38.5 to 18.7 pg/mL), along with improvements in DAS28 (4.5 to 2.8), HAQ-DI (1.3 to 0.7), and VAS scores for pain and stiffness. Functional gains were evident in reduced TUG test times (10.2 to 7.6 sec) and increased grip strength (19.4 to 24.3 kg), significantly outperforming the control group in all domains. Conclusion: Targeted inhibition of miR-155 in early RA significantly reduces inflammation and enhances clinical and functional outcomes when paired with physical therapy. This approach may represent a promising adjunctive treatment for early-stage RA.