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Objectives Evidence regarding therapeutic strategies and long-term treatment outcomes for autoimmune hemolytic anemia(AIHA) in lupus patients remains limited, and data defining the optimal timing for steroid-sparing immunosuppressive(IS) therapy are scarce.This study aimed to evaluate treatment outcomes and identify predictors of response in patients with lupus-associated severe AIHA.Methods In this retrospective multicenter study, patients who fulfilled the 2019 SLE classification criteria and were diagnosed with AIHA were included, with a minimum follow-up of six months. Treatment responses and relapse histories were assessed.Results The study included 90 patients (female/male:82/8) with SLE-associated AIHA, who were followed for a median 53.1 months (IQR 22.6-94.2). The mean age was 39.8±15.3 years, and the median baseline hemoglobin level was 7.0 g/dL (IQR 5.87–7.8). Initial treatment for AIHA consisted of corticosteroids(CS) alone in 88.9% of patients (48 high-dose/pulse,31 moderate,1 low),CS combined with IVIg in 10%, and IVIg alone in 1.1%. An early (first-month) response to initial therapy was observed in 92.2% of patients, including 48 complete and 35 partial responses. Since AIHA diagnosis, 77 patients (85.5%) received early steroid-sparing IS agent or underwent splenectomy, whereas 13 patients were treated with CS alone. Patients who did not receive early IS therapy had significantly higher rates of late treatment failure or relapse compared to those who received early IS therapy (53.8%vs.16.9%, p=0.006) ( table 1,figure1) Early IS therapy was the only independent predictor of positive treatment response (p=0.006;OR=5.7,95%CI:1.6-19.9). The presence of less severe anemia at baseline was not significantly associated with treatment outcomes (hemoglobin 8–10g/dL[n=19] vs.<8 g/dL[n=71], p=NS). Second-line therapy was required in 20 patients, achieving an overall response rate of 80%. At the end of follow-up, 2 patients (2.2%) were refractory and 7(7.7%) had died,with no deaths attributable to AIHA.Abstract PO:10:272 Table 1Long-term treatments and response rates in AIHAAbstract PO:10:272 Figure 1Response rates to first-line therapy in patients with AIHAConclusions In the treatment of SLE-associated AIHA, early response to CS therapy was favorable, and the early use of steroid-sparing IS agents was identified as an independent factor associated with lower rates of treatment failure.Additionally, patients with less severe anemia appeared to have a comparable prognosis. These findings underscore the importance of early initiation of IS therapy and highlight the need for further research to refine the hemoglobin threshold for treatment initiation.