OP0187 IDENTIFYING A POPULATION OF PATIENTS FOR INTENSIVE FIRST-LINE THERAPY IN SLE: A CLINICAL AND BIOMARKER MODEL TO PREDICT THE NEED FOR INTENSIVE THERAPY
Authors: P. Intapiboon, S. U. Hassan, J. Arnold, L. M. Carter, K. Mahmoud, E. M. Vital, M. Y. MD Yusof
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The consideration of intensive therapy in SLE depends on disease severity, disease resistance, or reimbursement issues. Evaluating the baseline predicting factors for earlier decisions to initiate intensive therapy in high-risk SLE patients is an unmet need. Thus, we assessed the predictors of intensive therapy requirements for such a novel early intensive therapy strategy to prevent severe SLE and accrual damage. <h3>Objectives:</h3> To investigate the clinical and biomarkers factors predicting time-to-requirement for intensive therapy from SLE diagnosis. <h3>Methods:</h3> We conducted a retrospective longitudinal study of all patients with a diagnosis of SLE from two Leeds Cohort databases (CONVAS and DEFINITION) for over 30 years follow-up. Data collection included demographics, clinical characteristics, the 2019 EULAR-ACR classification criteria score, the SLEDAI-2K score, and routine immunological tests. The main outcome was the time from SLE diagnosis to intensive therapy initiation (cyclophosphamide, rituximab, belimumab, or other biologic agents). Univariable analysis (UVA) and multivariable (MVA) Cox proportional hazards regression models were used to test the potential predictors of the main outcome. <h3>Results:</h3> 229 SLE patients were included; 91.3% were female, and mean (SD) age at diagnosis was 38.8 (14.7) years. Total follow-up: 3448 patient-years; median (IQR) follow-up time was 11.6 (6.7, 21.4) years. Overall, intensive therapy was initiated in 110 (48%) patients; 39 (17.0%) within 1 year and 55 (24.0%) within 2 years of diagnosis. Median (IQR) time-to-intensive therapy was 2 (0.5, 8) years. Rituximab (51.8%) was the most common intensive therapy, followed by cyclophosphamide (40.9%). During the first 2 years of diagnosis, in UVA, baseline anti-Ro antibody positivity, low complement levels, EULAR-ACR criteria score ≥20, and higher cSLEDAI score were associated with increased risk. We identified cSLEDAI score of ≥9 in ROC analysis as the optimum cut-off. In MVA, baseline low complement levels and cSLEDAI score ≥9 were associated with increased risk of intensive therapy requirement (Table 1). This was supported by the 2-year Kaplan-Meier intensive therapy-free survival graph between Group 1: low cSLEDAI score ≥9 and low complement levels, and Group 2: cSLEDAI &lt;9 or normal complement levels (Figure 1). <h3>Conclusion:</h3> Nearly half of SLE patients required intensive therapy; it was administered early in the disease course, and initial low complement levels, or a severe disease activity at diagnosis predicted its use. At present, it is unclear whether patients should receive initial antimalarials, then immunosuppressants, then biologic therapies, or whether some patients should receive a first-line biologic therapy. Our data suggest that patients with these predictive factors develop more severe SLE, fail conventional therapies, and, therefore, are suitable for first-line biologic therapy. Validation of our findings may provide a strategy to prevent severe SLE. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Porntip Intapiboon Novartis,Amgen, Sabih Ul Hassan: None declared, Jack Arnold Alumis, Lucy M. Carter Alumis, Khaled Mahmoud: None declared, Edward M. Vital Roche, GSK, AstraZeneca, Aurinia Pharmaceuticals, Lilly and Novartis., Roche, AstraZeneca and Sandoz., Md Yuzaiful Md Yusof Roche, Novartis and Alumis., Aurinia Pharmaceuticals and UCB.