FRI0666 Circulating mir-99b-5p as a predictor of erosion progression in early rheumatoid arthritis: a 1-year follow-up study by hr-pqct
Authors: J. Yue, J. F. Griffith, J. Xu, F. Xiao, L. Shi, D. Wang, P. C. Wong, E. K. Li, M. Li, T. K. Li, T. Y. Zhu, V. Hung, L. Qin, L.-S. Tam
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Bone erosion is a key feature of RA reflecting both disease severity and progression. HR-pQCT is an in-vivo clinical imaging system allowing detailed analysis of bone structure, including bone erosion. Several circulating microRNAs have already been suggested as potential biomarkers in RA. <h3>Objectives:</h3> To determine whether plasma cell-free circulating miRNAs are 1) associated with bone erosion at presentation and 2) predictive of erosion progression at 12 months as determined by HR-pQCT in patients with early rheumatoid arthritis (ERA). <h3>Methods:</h3> In this prospective study, 124 ERA patients were treated with a tight control protocol aiming at remission by using conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs). The second metacarpophalangeal joint (MCP2) was assessed for erosions by HR-pQCT at baseline and after 12 months. Plasma cell-free circulating miRNAs at baseline were identified by microRNA array in 10 treatment-naïve ERA patients with maximal erosion volume at MCP2; in 10 treatment-naïve ERA patients without erosion; and in 6 age- and sex-matched healthy controls. The 4 most dysregulated miRNAs were identified by TaqMan<sup>®</sup> qRT-PCR in these same 20 ERA patients. Thereafter, the expression of these 4 selected miRNAs was validated in all 124 ERA patients at baseline. <h3>Results</h3> Of the 377 screened miRNAs, 155 miRNAs were detectable. 94 (60.6%) of these detectable miRNAs were upregulated in ERA patient with erosions, with 13 (8.4%) upregulated more than twofold. 61 (39.4%) miRNAs were downregulated in ERA patients with erosions, with 6 (3.9%) downregulated more than twofold. A total of 16 miRNAs were differentially expressed (<i>P</i>&lt;0.05) and 4 were possibly differentially expressed (P ≤0.1) between ERA patients with and without erosions. At baseline, expressions of miR-143–3p, miR-145–5p and miR-99b-5p were significantly higher in ERA patients with erosions than those without erosions (<i>P</i>&lt;0.05 for all). After 12 months of csDMARDs treatment, 31.7%, 47.7%, and 20.6% of the ERA patients had erosion progression, stable erosion and partial erosion repair respectively. Logistic regression analysis revealed baseline expression of miR-99b-5p to be an independent predictor of erosion progression at 12 months (Exp [B]= 4.203, 95% CI 1.166–15.147, <i>P</i>=0.028) (table 1). <h3>Conclusions:</h3> Increased level of cell-free circulating miR-99b-5p was associated with erosions at presentation in ERA patients and could predict erosion progression as assessed by HR-pQCT over a period of 12 months, indicating that it may well serve as a biomarker of poor response to csDMARDs. Whether early biologic DMARDs use in these miR-99b-5p positive patients could reduce or prevent progression of erosion will need to be addressed in future studies. <h3>Acknowledgements:</h3> This study was partly supported by the Health and Medical Research Fund (project no 10110071). <h3>Disclosure of Interest:</h3> None declared