AB0434 EFFICACY AND SAFETY OF OBINUTUZUMAB IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS WITH SECONDARY NON-RESPONSE TO RITUXIMAB.

Background Secondary inefficacy characterized by infusion reactions and anti-drug antibodies occur in 14% of SLE patients treated with repeat rituximab courses(1). Obinutuzumab is a next-generation humanized type-2 anti-CD20 therapy licensed for hematological malignancies which may overcome this issue(2). Objectives We set out to evaluate the clinical efficacy safety obinutuzumab cohort resistant patients. Methods collated data from receiving secondary non-response BILAG centres. Disease activity was assessed using BILAG-2004, SLEDAI-2K serology before, 6 months after, 2x1000mg infusions alongside methylprednisolone 100mg. Flow cytometry where possible carried multiple gating highly sensitive strategy. Results All 9 included study received concomitant oral immunosuppression. At post-obinutuzumab, there were significant reductions median 12 (p=0.014) total BILAG-2004 score 21 2 (p=0.009). Complement C3 dsDNA titres improved significantly (both p=0.04). Non statistically numerical improvements seen C4 levels. Of 8/9 prednisolone at baseline (all >10mg/day), 5/9 had their dose reduced months; 4/8 on 5mg/day Lupus Low Activity State. After obinutuzumab, 6/9 peripheral B-cell achieved complete depletion including 4/4 assays. 1/9 non-responder required cyclophosphamide therapy. 1 unvaccinated patient died COVID-19. Table 1. Baseline characteristics, disease steroid doses before after last obinutuzumab/rituximab. Patient Ethnicity duration (Years) Age Total Obi Prednisolone (mg) South Asian 10.8 36.4 18 14 8 10 5 6.3 24.4 24 4 30 3 11.9 34.8 29 8.2 41.9 0 15 6.8 29.4 32 50 60 White European 17.5 37.0 7 16.9 30.0 Caribbean 6.2 44.2 25 13 2.6 21.0 16 Median (Q1, Q3 ) NA (6, (29,37 (12, (1, (10, (4, (5, Conclusion appears be effective steroid-sparing renal non-renal rituximab. shown severe disease. Therefore, those previous responsiveness depletion, switching humanised logical approach following loss off efficacy. References [1]Vital EM, Dass S, Buch MH, Henshaw K, Pease CT, Martin MF, et al. B cell biomarkers responses systemic lupus erythematosus. Arthritis Rheum [Internet]. 2011 Oct [cited 2020 12];63(10):3038–47. Available from: https://pubmed.ncbi.nlm.nih.gov/21618204/ [2]Hassan SU, Md Yusof MY, Emery P, Vital EM. Biologic Sequencing Systemic Erythematosus: Non-response Rituximab, Switching Humanised Anti-CD20 Agent Is More Effective Than Belimumab. Front Med Aug 27 Sep 2];7:498. https://www.frontiersin.org/article/10.3389/fmed.2020.00498/full Disclosure Interests Jack Arnold: None declared, Shouvik Consultant of: Roche, Abbvie, UCB & Chugai, Employee Honoraria Sarah Twigg: Colin Jones: Benjamin Rhodes: Peter Hewins: Mithun Chakravorty: Philip Courtney: Michael Ehrenstein Grant/research support GSK, Has honoraria Yuzaiful Yusof: Edward Roche