AB0385 BARICITINIB LEADS TO RAPID AND PERSISTENT RESOLUTION OF SYNOVITIS AS MEASURED BY HAND MRI IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS (RA) FAILING cs/bDMARD THERAPY

Background RA is characterized by synovial inflammation resulting in local bone loss [1]. Inhibitors of JAK/Stat pathways, such as baricitinib, demonstrated efficacy reducing signs and symptoms clinical trials, however, little known about their effects on synovitis structure [2]. Preclinical observations suggest a positive effect JAK inhibitors mass microstructure, however no prospective, interventional trial has been performed so far [3]. Objectives The aim this study to evaluate the baricitinib (synovitis osteitis) (erosions) patients failing cs/bDMARD therapy using hand MRI. Methods BAREBONE interventional, open label, monocentric single center (EUDRACT 2018-001164-32 / NCT03701789 ) assess (4mg/day) MRI with active RA. Besides demographic characteristics, joint was assessed magnetic resonance imaging (MRI) 1.5 Tesla scanner (Siemens Magnetom Aera T1w TSE cor, T2w TIRM fat-sat trans, trans + cor after KM;). at baseline, week 24 48. Scans were for synovitis, osteitis erosions RAMRIS scoring system two independent blinded readers (SK SB). Intraclass correlation coefficients calculated total erosion subscores second step differences between cs bDMARD failure elaborated. Variables are summarized descriptively means 95% bootstrap confidence intervals continuous outcomes number percentages categorical outcomes. Results Thirty- screened 30 included (age: 53.4 [SD 12.6] years; sex: f/m N 24/6; disease duration: 3 [IQR 2.0 – 8.0] biologic naïve/bDMARD 16/14). 27 completed while data available Demographics characteristics can be seen Table 1. Total scores slightly decreased from 20.6 (95% CI 14.4 -27.8) baseline (BL) 18.3 (11.5 -26.5) subscore mainly contributed reduction significantly improving 5.3 (4.0 - 6.8) BL 2.7 (1.5 4.0) 48 score change -2.9 (-4.0 -1.8). At 48, 12 (44.4%) had compared only BL. In contrast, marginally 4.9 (2.2 8.4) 4.0 (1.9 6.7) remained stable over 48-week observation time. A significant difference naïve -3.8 (-5.2 -2.6) vs -1.0 (-2.2 0.4 could observed 48). With respect activity, DAS 28 4.8 (4.5 5.1) 2.9 (2.5 3.3) Detailed results found 1 Figure coefficient (95%CI) high both 0.997 (0.994 0.998). Demographics, ESR, subset shown well improvement resolution synovitis. Baseline Week Age Mean [SD] 53.5 (12.6) Gender female n [%] (80.0) male 6 (20.0) Disease duration, years Median (IQR) 3.0 (2.0-8.0) DAS-28 ESR [95%CI] (2.7 (2.4 3.0) (100.0) (93.3) (88.9) (14.4 27.6) 18.4 (12.6 25.4) 26.5) 0.0 (0.0 0.0) -2.1 -0.4) -3.9 (-7.2 -0.5) (3.9 6.9) 3.5 4.9) -1.8 (-2.5 -1.0) -1.8) improved 10 (33.3) 13 (48.1) resolved (44.4) 3.7 6.2) -0.9 (-3.1 1.0) -1.9 (-5.7 1.1) 2 (6.7) 4 (14.8) 10.4 (7.3 14.6) 11.2 (7.7 15.0) 11.6 (7.5 16.6) 0.6 (0.1 1.2) 0.9 2.1) worsened (11.1) Conclusion Our shows that primarily reduces have previously failed csDMARD particularly who naïve. References [1]McInnes, I.B. G. Schett, pathogenesis rheumatoid arthritis. Engl J Med, 2011. [2]Genovese, M.C., et al., Baricitinib Patients Refractory Rheumatoid Arthritis. 2016 [3]Adam, S., inhibition increases steady-state conditions ameliorates pathological stimulating osteoblast function. Sci Transl 2020. Acknowledgements Lilly Deutschland GmbH funded Barebone Disclosure Interests Stephan Kemenes: None declared, Sara Bayat: David Simon Speakers bureau: Pharma GmbH, Janssen, Consultant of: BMS, Pfizer, Sanofi, Abbvie, Medac, Novartis, GileaBMS, Gilead, Amgen d, , Grant/research support from: Lilly, Gerhard Krönke GSK, Daniela Bohr: Larissa Valor: Fabian Hartmann: Louis Schuster: Koray Tascilar Gilead speaker, UCB, Georg Schett Roche, AMGEN, Chugai, Arnd Kleyer