P241 Efficacy of obinutuzumab in systemic lupus erythematosus patients with secondary non response to rituximab

Abstract Background/Aims Rituximab is a chimeric type-1 anti-CD20 monoclonal antibody approved by NHS England for refractory SLE. Secondary inefficacy with infusion reactions and anti-rituximab-antibodies occurs in 14% of re-treated patients. Obinutuzumab next-generation humanised type-2 licensed the treatment haematological malignancies. Methods We collated data from nine SLE patients receiving off-label obinutuzumab secondary non-response to rituximab across six centres (Leeds, Bradford, York, UCL, Birmingham Nottingham). Disease activity was assessed using BILAG-2004 SLEDAI-2K serology local diagnostic laboratories before, 6 months after, 2x1000mg infusions 2 weeks apart alongside methylprednisolone 100mg. Results All received concomitant oral immunosuppression prednisolone. 6/9 hydroxychloroquine. The median number cycles before therapy 2.5. Before had BILAG A/B mucocutaneous, musculoskeletal 4/9 renal. after 1/9 B no 2/9 Median dsDNA reduced 118 83 IU/mL, C3 increased 0.53 1.02g/L C4 0.095 0.23g/L. Prednisolone dose 5/9 patients; all 10mg or more. After obinutuzumab, 5mg were Lupus Low Activity State (LLDAS). Patient 5 did not respond required further cyclophosphamide at 4 months. partial renal response but transplantation, which successful. 8 responded well died severe COVID-19 infection (unvaccinated). B-cell achieved complete depletion including 4/4 highly sensitive assays. Conclusion These results demonstrate obinutuzumab’s efficacy rituximab. have disease few options, previous responsiveness depletion. Therefore, switching another this class mechanistically logical. appeared effective non-renal as steroid-sparing. Immunological markers also improved. generally tolerated will be investigated treatment-refractory lupus REGENCY ALLEGORY trials. Disclosure J.E. Arnold: None. S. Dass: Consultancies; Received consultancy fees Roche, Abbvie, UCB & Chugai. Honoraria; honoraria Twigg: C.H. Jones: B. Rhodes: P. Hewins: M. Chakravorty: Courtney: Ehrenstein: GSK. Grants/research support; funding Md Yusof: E. Vital: consulting GSK, Eli Lilly AstraZeneca. AstraZenec. research support Roche AstraZeneca (Paid University Leeds).