POS0975 PROFILING SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS STARTING TREATMENT WITH ANIFROLUMAB: INSIGHTS FROM THE MULTICENTER PROSPECTIVE OBSERVATIONAL REVEAL STUDY

Background: Anifrolumab (ANI) is a type I interferon receptor antagonist recently approved for the treatment of moderate to severe Systemic Lupus Erythematosus (SLE). While its efficacy and safety have been demonstrated in randomized controlled trials, real-world evidence remains limited. Objectives: The REal-world eVidencE of Anifrolumab in systemic Lupus erythematosus (REVEAL) study is a 5-year, multicenter, prospective observational study designed to collect real-world data on ANI use. The aim of the present work is to provide a phenotypic characterization of patients initiating ANI in routine clinical practice at referral centers for SLE management. Methods: Adult SLE patients, classified according to the 2019 EULAR/ACR criteria, were enrolled at ANI prescription and prospectively followed. At baseline, clinical and demographic characteristics, prior treatments and SLICC-DI scores were extracted from medical records. Current data on disease activity (SLEDAI-2K, SLE-DAS, Physician Global Assessment [PhGA], Cutaneous LE Disease Area and Severity Index [CLASI], joint count), concomitant therapies, and patients' quality of life (Patient Global Assessment [PtGA], Lupus Impact Tracker [LIT] and Functional Assessment of Chronic Illness Therapy - Fatigue Scale [FACIT-F]) were collected. Differences between patients initiating ANI through the Early Access Program (EAP) and those starting treatment post-marketing authorization were explored. Correlations between disease activity and damage indices and Patient Reported Outcomes (PROs) were further investigated. Results were expressed as median (IQR) or mean±SD for continuous variables and as percentage for categorical variables. Intergroup comparisons were assessed by using chi-square and Mann-Whitney tests, as appropriate. Spearman's coefficient was used to analyze the correlations between variables. Statistical significance was set at p <0.05. Results: A total of 134 patients from 17 centers were included, predominantly female (91.8%) and Caucasian (94.0%), with a median age of 47 years (IQR 36-54) and a median disease duration of 11 years (IQR 6-20). Three patients had Rhupus syndrome (2.2%), 16 had secondary antiphospholipid syndrome (11.9%) and 10 had associated Sjögren's syndrome (7.5%). The main indications for ANI were mucocutaneous (94/134, 70.1%) and articular manifestations (63/134, 47.0%), followed by haematological involvement (27/134, 20.1%). Haematological disease activity was mostly represented by leukopenia, although a non-negligible proportion of patients started ANI for thrombocytopenia (8/134, 6.0%). Nearly all patients had previously been treated with glucocorticoids (GCs, 98.5%), with more than half receiving a cumulative GCs dose greater than 10 g prednisone-equivalent (70/134, 52.2%). For 47 patients (35.1%) ANI was the first biological drug prescribed, and 8 (6.0%) were naïve to immunosuppressants (IS, including conventional, biologics and targeted synthetic DMARDs). Among patients non-naïve to biological therapy, belimumab was the most common prior biologic (78/87, 89.7%), followed by rituximab (19/87, 21.3%); notably, 20 patients of the whole cohort (14.9%) had received more than one bDMARD. Whereas most patients initiated ANI in combination with traditional IS (76/134, 56.7%), in 9 cases (6.7%) ANI was added to antimalarial monotherapy. Twenty-two patients (16.4%) started ANI within two years of SLE diagnosis. Slightly less than one-sixth of the patients had a previous history of Herpes Zoster (HZ, 20/134, 14.9%), while half had received at least one HZ vaccine dose prior to initiating ANI (67/134, 50.0%). Patients in the EAP subgroup (37/134, 27.6%), compared to the rest of the cohort, had more frequent prior exposure to csDMARDs (p=0.036) and bDMARDs (p=0.016) and had been treated with a higher number of csDMARDs (2.7±1.4 vs 2.1±1.3, p=0.023) and bDMARDs (1.1±0.7 vs 0.8±0.7, p=0.034). No further differences emerged between the two groups in terms of demographic and clinical characteristics and in relation to previous exposure to GCs. Table 1 depicts the detailed characteristics of the whole cohort. We observed a significant perception of disease burden in our patients, determined particularly by skin disease activity and joint pain. Indeed, in addition to observing correlations between PtGA and SLEDAI-2K, SLE-DAS and PhGA, we noticed a significant correlation between PROs and CLASI activity and tender joints. Extensive information on the correlations between activity and damage indices and patients' perspective are reported in Table 2. Conclusion: The REVEAL study provides one of the first real-world characterizations of ANI use in SLE management. Most patients in this cohort had longstanding, refractory disease, but a notable proportion started ANI within two years of SLE diagnosis or as their first bDMARD. Mucocutaneous and joint involvements remain the primary indications for ANI, but our cohort presents heterogeneous clinical and serological features, reflecting the complexity of SLE patients. Ongoing follow-up and prospective analysis will bridge gaps in real-world evidence, helping to identify patients most likely to benefit from ANI.