AB0777 IDENTIFICATION OF A MICRORNA SIGNATURE PREDICTIVE OF CLINICAL RESPONSE TO TOFACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: E. Celletti, M. DI Penta, E. Sabatini, D. De Cesare, A. Dionisi, F. Cipollone
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Current therapeutic options for Rheumatoid Arthritis (RA) include a wide range of disease-modifying antirheumatic drugs (DMARDs). Unfortunately, there are still no reliable indicators of future clinical response to therapy and the actual process of therapeutic selection in RA patients is largely empirical. In recent years, the study of circulating miRNAs as biomarkers of disease has become prominent due to their easy accessibility, good stability, and association with specific diseases. Few studies are available about a possible role of microRNAs as predictors of therapeutic response to biologic (1-2) and targeted synthetic DMARDs (3). <h3>Objectives:</h3> In this prospective observational study, we investigated the changes in circulating miRNAs in RA patients before and after six months of treatment with tofacitinib (TOF), a Janus kinase inhibitor indicated for treatment of moderate to severe RA. The endpoint of the study was to identify a miRNA signature predictive of clinical response to tofacitinib in patients with RA. <h3>Methods:</h3> Thirty consecutive patients were recruited into this study. Demographics, medical history, serum markers (rheumatoid factor, anti-citrullinated protein antibodies), disease activity indexes (tender joint count, swollen joint count, visual analog scale for pain, erythrocyte sedimentation rate, C-reactive protein level), Health Assessment Questionnaire Disability Index (HAQ-DI score), MOS 36-item short form health survey (SF-36), concomitant anti-rheumatic treatments (eg, methotrexate, leflunomide) of each patient were collected after enrolment. We calculated DAS28-ESR, DAS28-CRP, Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI). We also performed a grayscale and power-doppler ultrasound with transverse and longitudinal scans of the volar and dorsal parts of the metacarpophalangeal, proximal interphalangeal, radiocarpal, intercarpal and metatarsophalangeal joints. A widemiRNA expression profiling was performed before and after six months of tofacitinib treatment. <h3>Results:</h3> Compairing the resulting data from two different pools, ten microRNAs emerged to be differentially expressed before and after the treatment with tofacitinib: hsa-let-7a-5p; hsa-miR-126-3p; hsa-miR-150-5p; hsa-miR-221-3p; hsa-miR-223-3p; hsa-miR-23b-3p; hsa-miR-24-3p; hsa-miR-451a; hsa-miR-93-3p; has-miR-125b. Two of the ten miRNAs tested showed statistically significant changes before and six months after treatment with Tofacitinib: miR-223 and miR-451 (Figure 1). For both of them we reported an increase in the dose at T1, with an inverse correlation between miR-451 and DAS28-CRP (Figure 2). <h3>Conclusion:</h3> miR-451 could represent a useful biomarker of therapeutic response in RA patients. Further studies are needed to confirm its possible prognostic and/or predictive role in therapeutic response in subjects treated with tofacitinib. <h3>REFERENCES:</h3> [1] Castro-Villegas C, Pérez-Sánchez C, Escudero A, et al. Circulating miRNAs as potential biomarkers of therapy effectiveness in rheumatoid arthritis patients treated with anti-TNFα. Arthritis Res Ther 2015; 17: 49. [2] Sode J, Krintel SB, Carlsen AL, Hetland ML, Johansen JS, Hørslev-Petersen K, Stengaard-Pedersen K, Ellingsen T, Burton M, Junker P, Østergaard M, Heegaard HH. Plasma microRNA profiles in patients with early rheumatoid arthritis responding to adalimumab plus methotrexate vs methotrexate alone: a placebo-controlled clinical trial. J Rheum 2018; 45: 53-61. [3] Fernández-Ruiz JC, Ramos-Remus C, Sánchez-Corona J, Castillo-Ortiz JD, Castaneda- Sánchez JJ, Bastian Y, Romo-García MF, Ochoa-González F, Monsivais-Urenda AE, González-Amaro R, Enciso-Moreno JA, Castaneda-Delgado JE. Analys of miRNA expression in patients with rheumatoid arthritis during remission and relapse after a 5-year trial of Tofacitinib treatment. Int Immunopharm 2018; 63: 35-42. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>