Ab1103 General Clinical Characteristics and Damage Accrual in Patients With Prominent Systemic Inflammatory Features: Preliminary Data From a Monocentric Lupus Cohort

Background: Systemic lupus erythematosus (SLE) is a multi-organ disease characterised by generalised immune dysfunction and dominated by autoimmunity. High-grade systemic inflammation, resembling autoinflammatory (AI) disorders might complicate and overlap with the classical lupus phenotype (1, 2). Patients with these characteristics amid the spectrum of SLE constitute an ill-defined subgroup despite a potentially higher risk of morbidity and mortality. Objectives: To characterise the clinical profile and long-term SLE outcomes of patients with AI features within a monocentric SLE cohort. Methods: By reviewing the clinical characteristics of about 300 patients with SLE we identified a group of subjects with AI features (AIG), meeting the following criteria: 1) fever without infection or with incomplete antibiotic response, lasting more than two weeks and/or resistant to 0.5mg/kg prednisone-equivalent steroid therapy; 2) history of non-infectious fever ≥40°C or 3) of Macrophage Activation Syndrome (MAS); 4) erythrocyte sedimentation rate (ESR) higher than 75mm/h in at least three consecutive visit, 5) C-reactive protein higher than twice the upper level of normality in at least three consecutive visits, excluding infections; 6) ferritinaemia higher than 600 ng/ml despite 0.5mg/kg prednisone-equivalent steroid therapy. We collected demographic, clinical and treatment data from a series of 140 consecutive patients without these criteria, which constituted a Control Group (CG). Damage accrual was measured with the SLE International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Results: Thirteen subjects met the inclusion criteria for AIG. The main AI manifestations were non infectious and/or steroid resistant fever longer than two weeks (n=8, 62%) followed by persistent ESR (n=7, 54%). MAS, persistent CRP and Ferritin elevation had a prevalence of 31% (n=4) each. Five subjects (39%) had concomitant SLE and AI onset (Table 1). Compared to the CG, SLE patients in the AIG had a significant higher proportion of constitutional symptoms (77% vs 38%, p=0.032), including fever (92% vs 16%, p<0.001), as expected. Gastrointestinal symptoms were also more frequent in the AIG compared to CG (31% vs 2%, p<0.001). A lower antiphospholipid antibody prevalence was found in AIG, especially with regard to anticardiolipin antibodies (0% vs 32%; p=0.015). No other differences were identified in terms of demographics, clinical and treatment features among the two groups. AIG patients with SLE had a higher risk of SDI progression over time compared to CG patients (HR 5.2, 95%C.I. 1.4-19.5 p=0.012; Figure 1). Conclusion: AI features constitute an uncommon, yet clinically significant aspect of the broad spectrum of SLE manifestations. SLE patients with AI manifestations show a distinct clinical profile and accrue damage more rapidly compared to patients without these clinical characteristics. These data highlight a still unmet need in the care of patients with SLE and suggest that unique pathogenic events occur in patients with AI features, which might insufficiently be tackled by current diagnostic and treatment strategies. REFERENCES: [1] Gavand PE, et al., Autoimmun Rev. 2017 [2] Mahajan VK, et al., World J Clin Cases. 2023 Acknowledgements: NIL. Disclosure of Interests: Giovanni Benanti: None declared, Giuseppe Alvise Ramirez Astrazeneca (lessons), Astrazeneca, GSK (advisory boards), Astrazeneca (financial support for publication), Costanza Vitellaro: None declared, Chiara Calabrese: None declared, Serena Nannipieri: None declared, Luca Moroni Astrazeneca (lessons), Astrazeneca, GSK (advisory boards), Astrazeneca (financial support for publication), Enrica Bozzolo: None declared, Marco Matucci-Cerinic: None declared, Lorenzo Dagna: None declared.