UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Efficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab

Arnold, J; Dass, S; Twigg, S; Jones, CH; Rhodes, B; Hewins, P; Chakravorty, M; ... Vital, EM; + view all (2022) Efficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab. Rheumatology , 61 (12) pp. 4905-4909. 10.1093/rheumatology/keac150. Green open access

[thumbnail of Ehrenstein_Obinutuzumab case series paper 2021_0.11Final.pdf]
Preview
Text
Ehrenstein_Obinutuzumab case series paper 2021_0.11Final.pdf - Accepted Version

Download (121kB) | Preview

Abstract

OBJECTIVE: 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.

Type: Article
Title: Efficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/rheumatology/keac150
Publisher version: https://doi.org/10.1093/rheumatology/keac150
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: SLE, biologics, rituximab, Humans, Rituximab, COVID-19, Lupus Erythematosus, Systemic, Methylprednisolone, Treatment Outcome
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10180137
Downloads since deposit
20Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item