Arnold, JackDass, ShouvikTwigg, SarahJones, Colin HRhodes, BenHewins, PeterChakravorty, MithunCourtney, PhilEhrenstein, MichaelMd Yusof, Md YuzaifulVital, Edward M2023-10-162023-10-162022-11-28Arnold J, Dass S, Twigg S, Jones CH, Rhodes B, Hewins P, Chakravorty M, Courtney P, Ehrenstein M, Md Yusof MY, Vital EM. Efficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab. Rheumatology (Oxford). 2022 Nov 28;61(12):4905-4909. doi: 10.1093/rheumatology/keac1501462-03241462-033210.1093/rheumatology/keac15035266512http://hdl.handle.net/20.500.14200/2552Objectives: Secondary inefficacy with infusion reactions and anti-drug antibodies (secondary non-depletion nonresponse, 2NDNR) occurs in 14% of SLE patients receiving repeated rituximab courses. We evaluated baseline clinical characteristics, efficacy and safety of obinutuzumab, a next-generation humanized type-2 anti-CD20 antibody licensed for haematological malignancies in SLE patients with 2NDNR to rituximab. Methods: We collated data from SLE patients receiving obinutuzumab for secondary non-response to rituximab in BILAG centres. Disease activity was assessed using BILAG-2004, SLEDAI-2K and serology before, and 6 months after, obinutuzumab 2× 1000 mg infusions alongside methylprednisolone 100 mg. Results: All nine patients included in the study received obinutuzumab with concomitant oral immunosuppression. At 6 months post-obinutuzumab, there were significant reductions in median SLEDAI-2K from 12 to 6 (P = 0.014) and total BILAG-2004 score from 21 to 2 (P = 0.009). Complement C3 and dsDNA titres improved significantly (both P = 0.04). Numerical, but not statistically significant improvements were seen in C4 levels. Of 8/9 patients receiving concomitant oral prednisolone at baseline (all >10 mg/day), 5/8 had their dose reduced at 6 months. Four of nine patients were on 5 mg/day and were in Lupus Low Disease Activity State following obinutuzumab. After obinutuzumab, 6/9 patients with peripheral B cell data achieved complete depletion, including 4/4 assessed with highly sensitive assays. Of the nine patients, one obinutuzumab non-responder required CYC therapy. One unvaccinated patient died from COVID-19. Conclusions: Obinutuzumab appears to be effective and steroid-sparing in renal and non-renal SLE patients with secondary non-response to rituximab. These patients have severe disease with few treatment options but given responsiveness to B cell depletion, switching to humanized type-2 anti-CD20 therapy is a logical approach.en© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.OrthopaedicsArticle