POS1172 PLASMA STREM1 AND IL-6 DETERMINATION IDENTIFY DISTINCT SUBSETS AND IMPROVE CLINICAL MANAGEMENT IN SPONDYLOARTHRITIS: A CROSS-SECTIONAL STUDY
Authors: E. Gremese, S. Perniola, B. Tolusso, C. DI Mario, L. Parisio, D. Campobasso, D. Bruno, M. Gessi, G. Privitera, S. Varca, R. Benvenuto, L. Guidi, S. Alivernini, D. Pugliese
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Spondyloarthritis (SpA) is a group of diseases characterized by heterogeneous manifestations including Inflammatory Bowel Diseases (IBD). SpA clinical manifestations, laboratory and imaging features might be influenced by IBD, sharing some pathogenetic characteristics that allow to identify potential common biomarkers for clinical management. <h3>Objectives:</h3> To define clinical, immunological and synovial features in SpA associated or not with IBD and to identify putative biomarkers useful to predict SpA response. <h3>Methods:</h3> Fifty-three SpA patients (29 SpA associated to IBD and 24 SpA not associated) and 50 IBD-only patients (Control group; 17 ulcerative colitis and 33 Crohn's disease) with active disease and candidate to start a biological treatment were enrolled. Demographic and clinical features were collected for each patient. Plasma IL-6, IL-17A, TNF-alpha and sTREM1 levels were measured for each enrolled patient. Moreover, 42 SpA patients underwent synovial membrane biopsy to assess synovitis degree, using the Krenn Score (KSS) [1] and to immunohistochemistry (IHC) to assess CD68+, CD20+ and CD3+ cells infiltrate. After study entry, each SpA patient was treated according to the ASAS-EULAR recommendations and was followed every 4 months to assess clinical response in terms of ASDAS-CRP or DAS28-CRP at 4 months follow-up. <h3>Results:</h3> Considering the whole cohort of patients (median age: 52 (40-60) years; 58.5% female; median BMI: 24.6 (21.3-27.7) kg/mq; 43% csDMARDs users, 34% bDMARDs naïve; 48% SpA patients started a TNFi, 20% IL-17i, 16% IL-12/23i and 16% JAKi), having concomitant articular and intestinal involvement was associated with higher plasma levels of inflammatory cytokines, regardless of treatment. In particular, plasma IL-6 and sTREM1 levels were higher in SpA than in IBD (p&lt;0.0001 and p=0.001, respectively), identifying a specific IL-6 cut-off of 2.715 pg/ml [AUC: 0.809, 95%CI (0.708-0.910), p&lt;0.0001], significantly discriminating SpA patients in IBD cohort. Considering intestinal involvement, SpA without concomitant IBD showed higher KSS compared to SpA with IBD (p=0.042) finding direct correlations between KSS and C-Reactive Protein (R=0.455, p=0.003) and sTREM1 plasma levels (R=0.397, p=0.01) in the whole SpA cohort. Considering articular phenotypes, SpA with only axial involvement (axSpA) showed a distinct cytokines profile compared to patients with only peripheral SpA (perSpA) regardless of intestinal involvement. Particularly, axSpA had lower TNF-alpha and sTREM1 plasma levels compared to perSpA (p=0.036 and p=0.008, respectively) identifying a specific sTREM1 cut-off value of 193.50 pg/ml [AUC: 0.900, 95%CI (0.752-0.999), p: 0.011], which enable to discriminate among these two articular phenotypes within the SpA spectrum. Furthermore, in SpA cohort, sTREM1 plasma levels directly correlated with disease activity parameters (e.g., ASDAS-CRP: R=0.483, p=0.002; DAS28-CRP: R=0.582, p&lt;0.0001) and synovitis degree (R=0.397, p=0.01), in particular with CD20+ cells (R=0.401, p=0.021) and CD138+ cells (R=0.468, p=0.005) infiltrates. Finally, at 4 months of follow up, 69% SpA patients achieved clinical outcomes (respSpA), without significant differences in terms of baseline disease activity and synovitis degree compared to SpA patients not achieving the same clinical outcomes (no-respSpA). However, respSpA showed, at baseline, lower sTREM1 plasma levels than no-respSpA (p=0.022). Based on these results, having sTREM1 plasma level ≥550.0 pg/ml [AUC: 0.755, 95%CI (0.578-0.931), p=0.023] at the beginning of a new treatment was an independent factor associated with treatment refractoriness at 4 months [adjOR 23.826 (95%CI 1.578-359.751)], independently of age, sex, BMI and drug type. <h3>Conclusion:</h3> SpA with concomitant intestinal involvement presents specific clinical characteristics, plasma cytokines profile and synovial tissue features compared to SpA without IBD. Furthermore, IL-6 and sTREM1 plasma levels arose as putative biomarkers of patients' phenotyping and treatment management respectively in SpA. <h3>REFERENCES:</h3> [1] Alivernini S, et al. Arthritis &amp; Rheumatology 2021 <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>