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Objectives The timing of biologic initiation in systemic lupus erythematosus (SLE) may reflect disease phenotype and treatment strategy. We compared patients starting biologics within 2 years of diagnosis versus those initiating later.Methods We conducted a retrospective study of patients fulfilling the 2019 ACR/EULAR classification criteria for SLE who received Belimumab, Anifrolumab, or Rituximab between 2010 and 2025 at a university hospital. Patients were stratified into two groups: early initiation (<2 years from diagnosis) and late initiation (>2 years). Demographics, clinical manifestations, laboratory parameters (anti-dsDNA, C3, C4, hemogram), treatment discontinuations, and drug survival (Kaplan–Meier) were analyzed.Results A total of 84 patients were included, 16 in the early group and 68 in the late group. Females represented 81% and 93% of each group, respectively. Mean age at diagnosis was higher in early initiators (45.2 vs 32.8 years). Regarding biologic selection, Belimumab was used in 68.8% vs 52.9%, Anifrolumab in 12.5% vs 35.3%, and Rituximab in 18.8% vs 11.8% (early vs late).The most frequent clinical manifestations were articular, hematologic, and cutaneous involvement. While renal disease was more common in early initiators and cutaneous disease in late initiators, no statistically significant differences were observed across most domains, except for oral ulcers (more frequent in the late group (p=0.002)).Treatment discontinuations were comparable (31.2% vs 30.9%), mainly due to infections or lack of efficacy. Kaplan–Meier survival analysis showed no significant differences in 12-month persistence between groups.At baseline, early initiators had lower C3 levels. Over 12 months, this group showed a more pronounced increase in C3, suggesting faster complement recovery. Anti-dsDNA titers declined in both groups, with a stronger but non-significant trend toward reduction in early initiators. C4 and hematologic parameters remained stable and comparable between groups.Abstract PO:05:133 Figures and TableConclusions In this real-world-cohort, biologic initiation within the first two years of SLE diagnosis was associated with an older age at diagnosis, distinct drug selection patterns, and faster complement recovery, while overall clinical manifestations, treatment discontinuation, and persistence were similar between groups. These findings suggest that earlier biologic use may provide serologic advantages in selected SLE patients, supporting a tailored approach based on both timing and clinical phenotype.