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POS0444 PROFILING OF CIRCULATING miRNAs IN DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS

Biologic (b-) and targeted synthetic (ts-) disease-modifying antirheumatic drugs (DMARDs) have brought significant progress in the treatment of rheumatoid arthritis (RA), but a significant proportion of RA patients still remain symptomatic despite treatment according to current recommendations. These patients have recently been defined as “difficult-to-treat (D2T)” RA (1). There is evidence that miRNA expression may play a role in the diagnosis and therapy of RA (2).In a retrospective study, we analyzed patients’ blood samples prior to b-/ts-DMARD treatment and profiled circulating miRNAs to predict the development of D2T-RA.A total of 36 patients fulfilling the EULAR definition of D2T-RA (1) (mean age 59.1±10.7 yrs, 78% females), 36 patients with RA in sustained clinical remission on b-/ts-DMARDs at two consecutive examinations 12 wks apart (mean age 66.3±9.6 yrs, 78% females), and 36 healthy controls (mean age 61.1±7.7 yrs, 68% females) were included in the study. Blood samples were collected before initiation of b-/ts-DMARD. We profiled circulating miRNAs using the sequencing approach and differential expression analysis was performed using DESeq2 algorithm.The massive parallel sequencing of circulating miRNAs detected 814 quantifiable miRNAs and DESeq2 algorithm revealed 35 miRNAs with different concentrations in patients who developed D2T-RA compared to patients with RA who achieved sustained remission or healthy controls. Out of these miRNAs, miR-16-5p (1.5x) and miR-451a (2.1x) were downregulated and miR-126-3p (1.4x) was upregulated in D2T RA patients compared to controls. In addition, miR-101-3p (1.5x) was downregulated in D2T RA compared to RA patients. Except for miR-101-3p, these miRNAS have been previously associated with RA and might predict development of D2T disease prior to initiation of b-/ts-DMARD therapy.We found four miRNAs as potential biomarkers differentiating patients who are at risk to develop difficult-to-treat disease compared to patients who have a chance of sustained remission even before initiation of biological or targeted synthetic DMARDs. Further studies with larger sample size are needed to validated these data.[1]Nagy G, Roodenrijs NMT, Welsing PM, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021 Jan;80(1):31-35.[2]Filková M, Jüngel A, Gay RE, Gay S. MicroRNAs in rheumatoid arthritis: potential role in diagnosis and therapy. BioDrugs. 2012 Jun 1;26(3):131-41.This work was supported by the project SVV 260 523, BBMRI-CZ LM2018125, and a project of the MHCR for conceptual research development No. 023728.None declared.