OP0217 INVOLVEMENT OF LARGE JOINTS AT DISEASE PRESENTATION IS ASSOCIATED WITH DIVERSE HISTOPATHOLOGICAL FEATURES AND CLINICAL OUTCOMES IN EARLY RHEUMATOID ARTHRITIS

Background: The involvement of large joints at disease presentation in early Rheumatoid Arthritis (RA) has been associated with severe disease activity. At the same time, the clinical heterogeneity of RA is known to be mirrored by heterogeneity of synovial inflammation, with specific histological patterns (pathotypes) associated with treatment response and disease progression. However, it is not known whether joint size is associated with specific pathotypes. Objectives: To analyse histopathological features of synovial biopsies from joints of different sizes and establish the relationship with clinical outcomes in patients with early RA. Methods: 167 patients with early ( Results: The majority of synovial biopsies were performed on medium and small joints (60.6% and 19.4%) as compared to 21.3% in large joints (Table 1). At baseline, patients who underwent large joint biopsy showed significantly higher levels of inflammation (CRP 27.9±32.4 large, 20.7±26.9 medium, 10.4±9.8 small, p=0.007) and higher HAQ (1.8 ± 0.7 large, 1.4 ± 0.8 medium, 1.2 ±0.9 small, p=0.012), with no differences in DAS28. Significantly higher inflammatory scores and higher proportion of lympho-myeloid pathotype were observed in large joints (Table 1 and Figure 1). 6 months after treat-to-target treatment with csDMARDs, large joints patients had significantly higher HAQ and lower response (RR for low disease activity in large vs medium joints 0.5, 95%CI 0.2-0.9, p=0.03). Finally, differentially expressed genes by RNA-seq showed segregation according to joint size (Figure 2), with upregulation of genes of the Homeobox transcription factors family in large joints. Conclusion: Synovial biopsy of large joints as the most inflamed joints at disease presentation identified patients with early RA with specific histopathological features and clinical outcomes. Together with clustering of differentially expressed genes according to joint size, this suggests that the involvement of different joint compartments in early RA contributes to disease heterogeneity with potential physiopathological and clinical implications. References: [1]Humby et al Ann Rheum Dis. 2019 Jun;78(6):761-772 [2]Lewis et al Cell Rep. 2019 Aug 27;28(9):2455-2470.e5 [3]Linn-Rasker SP et al Ann Rheum Dis. 2007 May;66(5):646-50 Acknowledgments: PEAC http://www.peac-mrc.mds.qmul.ac.uk MRC grant 36661 & ARUK Grant 20022 F. Rivellese NIHR Fellowship TRF-2018-11-ST2-002 Disclosure of Interests: None declared