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Objectives To identify and characterize a subgroup of patients with SLE who an exceptionally sustained response to rituximab (’super-responders’).Methods Based on an observation by Vital and colleagues we conducted a retrospective analysis of 210 SLE patients treated between 2000-2022 with rituximab. Super-responders were defined by: (1) at least 3 years of follow-up without retreatment, (2) complete clinical response with no A/B scores in follow-up assessments using the British Isles Lupus Assessment Group 2004 Index, (3) normalization of anti-dsDNA antibodies and complement C3, (4) stable or reduced background immunosuppressive therapy. Demographic, clinical, serological, treatment and safety data were collected.Results Fourteen female patients (6.7%), met criteria for super-response ( table 1). Median age at rituximab initiation was 39 years, disease duration 5 years, follow-up 12 years. Manifestations included arthritis (92.9%), skin (85.7%), hematological (85.7%), nephritis (50%), serositis (42.8%), and neuropsychiatric lupus (21.4%). Anti-ENA antibodies were positive in 10: anti-Ro (64.3%), anti-La (28.6%), anti-RNP (35.7%), and anti-Sm (14.3%). Three (21.4%) had antiphospholipid antibodies; none were triple-positive/met antiphospholipid syndrome criteria.Thirteen received a single rituximab course; one a second cycle four years later. All maintained at least 3 years of remission without therapy escalation. Anti-dsDNA was measured by IgG/IgM ELISA in 10 (n<50 iu/ml) and IgG-specific ELISA in 4 (N<10iu/ml). Baseline medians were 110 UI/mL (IgG/IgM) and 64.8 (IgG), falling to 51.0 and 4.75 at 6 months. Mean C3 (n=0.9-1.8 g/l) increased from 0.86 to 1.1 mg/dL. B-cell depletion occurred in all, lasting 8 months (median); one remained depleted for >25 years.Prednisone was used in twelve patients, the mean dose decreasing from 9.4 mg/day at baseline to 4.7 mg/day at 6 months, and remaining stable; two followed a steroid-sparing strategy. Mycophenolate/azathioprine were used in four/five respectively, both with progressive dose reductions. One patient was on methotrexate, discontinued after rituximab. Three mild infections occurred; none required hospitalization. No serious adverse events or deaths were observed.Abstract PO:11:285 Table 1Conclusions A small subset of patients with SLE achieve prolonged remission after a single rituximab course, with normalized serologies and reduced treatment burden. Identifying this ‘super-responder’ phenotype may help guide patient selection for future B-cell depleting therapies.