Jiří Baloun1, Aneta Pekčcová2, Heřman Mann3, Jiří Vencovský4, Karel Pavelka5 and Ladislav Šenolt4, 1Institue of Rheumatology, Prague, Czech Republic, 2Institue of Rheumatology, Prague, Prague, Czech Republic, 3Institute of Rheumatology, Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic, Prague, Czech Republic, 4Institute of Rheumatology and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic, 5Institute of Rheumatology, Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic, Praha, Czech Republic
Background/Purpose: 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. There is evidence that miRNA expression may play a role in the diagnosis and therapy of RA.
Methods: 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. We screened circulating miRNAs using massive parallel sequencing and differential expression was computed by DESeq2.
Results: The massive parallel sequencing approach detected 814 miRNAs. The expression analyses 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 be associated with the development of D2T disease prior to initiation of b-/ts-DMARD therapy.
Conclusion: We discovered that miR-101-3p could differentiate patients with D2T disease from patients with sustained remission and represent a potential biomarker of D2T disease. However, these data need to be validated in further studies.
Acknowledgements: 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.
Disclosures: J. Baloun, None; A. Pekčcová, None; H. Mann, None; J. Vencovský, Abbvie, Biogen, Boehringer, Eli Lilly, Gilead, Kezar, Merck, Novartis, Octapharma, Pfizer, Takeda, UCB, Werfen, Argenx; K. Pavelka, MSD, Pfizer, Roche, Eli Lilly, Medac, UCB, SOBI, Biogen, Sandoz, Viatris; L. Šenolt, None.
