P160 Exceptional long-term remission after rituximab in systemic lupus erythematosus: identifying the super-responder phenotype

Abstract Background/Aims To identify and characterize a subgroup of patients with systemic lupus erythematosus (SLE) who had 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) ≥ 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 ≥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. Conclusion 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. Disclosure T. Pire-García: None. A. David Do Carmo: None. D.A. Isenberg: None.