Circulating microRNAs associated with tumour necrosis factor or fibloblast-like synoviocyte predict cartilage damage in early rheumatoid arthritis treated with methotrexate plus adalimumab: a subanalysis of the MIRACLE study

OBJECTIVES: This study aimed to explore the potential of plasma micro-ribonucleic acids (miRNAs) in predicting joint damage in patients with rheumatoid arthritis (RA). METHODS: This subanalysis of the MIRACLE study, a randomised, open-label, non-inferiority trial, explored and compared the efficacy and safety of treatment with adalimumab (ADA), an anti-tumour necrosis factor (TNF) α, plus a maximum tolerated dose of methotrexate (MTX) with a reduced dose of MTX in early RA. Plasma levels of miRNAs (miR-143-3p, miR-146a-5p, miR-155-5p, miR-182-5p, miR-21-5p, and miR-221-3p) and serum levels of inflammatory cytokines (interleukin-6 [IL-6], vascular endothelial growth factor [VEGF]) and matrix metalloprotease-3 (MMP-3) were measured at 24 weeks. Their association with joint destruction assessed by the modified total Sharp score [mTSS] over the 24-week period were analysed. RESULTS: A total of 134 patients who showed an inadequate response to MTX and started treatment with ADA were included in the analyses. Logistic regression analyses revealed that higher plasma levels of miR-143-3p, miR-146a-5p, miR-21-5p, and miR-221-3p were significantly associated with increases in mTSS >0.5 points during the observation period. In particular, positive correlation was derived from the progression of joint space narrowing. In contrast, MMP-3, VEGF, and IL-6 levels were not associated with joint destruction. Cartilage damage occurred mainly in patients treated with reduced dose of MTX. CONCLUSIONS: Higher circulating miRNA levels predicted subsequent cartilage damage in early RA treated with a TNF inhibitor in addition to MTX. Thus, the MTX dose at ADA initiation should not be reduced in patients with high microRNA levels.