Background: Between January 2020 and October 2023 9 SLE patients were treated at University College Hospital London (UCLH) with Obinutuzumab, a humanised anti-CD20 monoclonal antibody. Internal division funding was provided to individual patients following careful review based on an internal funding policy. Patients had previously failed rituximab for intolerance and/or secondary non-depletion and non-response.

Objectives: We aimed to evaluate the effectiveness and safety of Obinutuzumab in treating refractory lupus in this cohort of patients.

Methods: All patients with SLE treated with Obinutuzumab at UCLH with at least 6 months follow up after treatment were included. Patient electronic records were reviewed retrospectively. Data collected included patient demographics, disease duration, previous and concomitant treatments, clinical and laboratorial assessments of disease activity and any adverse events recorded on electronic notes following treatment with Obinutuzumab.

Results: 8/9 patients were female. Mean age was 31.1 years (range 19-48) at the time of treatment. Mean disease duration was 10.4 years (range 2-23). 7/9 patients had active renal involvement of SLE at the time of receiving Obinituzumab. All patients had previously received Rituximab for SLE. The mean number of courses of Rituximab (2x1g) was 3.5 (range from 1 to 6). In all cases, Rituximab was discontinued either due to intolerance and/or lack of biological response and consequent clinical response (non-depletion of B cells). All patients were on oral Prednisolone and at least one other long term immunomodulatory therapy (DMARDs or biologic) for SLE at the time of receiving Obinutuzumab. Patients had received an average of 5.7 previous therapies prior to Obinutuzumab (range 3-8). 7/9 patients had previously received Cyclophosphamide before having Obinutuzumab for the first time. Two patients had also received high dose intravenous steroids prior to treatment. One patient also had plasma exchange just prior to receiving Obinutuzumab (for catastrophic antiphospholipid syndrome). The Table 1 below demonstrates results pre-treatment, and at 6 months and 12 months post-treatment with Obinutuzumab, with some patients excluded for certain parameters due to an absence of appropriate baseline or follow-up readings.

All patients improved with treatment and all achieved partial renal response (>50% improvement in proteinuria) within 9 months (mean 4.6 months), one requiring additional Cyclophosphamide to achieve this. Mean number of inpatient days was 18.7 in the 12 months prior to Obinutuzumab and 8.7 in the 12 months post-treatment. Two patients developed infections requiring inpatient treatment in the year following their first Obinutuzumab cycle. No other major adverse effects were documented. 3/9 patients required escalation of lupus therapy within a year of Obinutuzumab.

Conclusion: Patients with SLE treated with rituximab can experience intolerance and/or secondary non-depletion/non-response to treatment often felt to be associated with the presence of HACAs and rapid clearance of the drug. Obinutuzumab, a type 2 humanised anti-CD20 mAb is a therapeutic alternative in these patients. Obinutuzumab is also likely to lead to better B cell depletion than rituximab with the potential of greater benefit. All the patients in our study had clinical and biochemical benefit from Obinutuzumab, evidenced by improvement in SLEDAI scores, proteinuria and serological markers of disease activity (dsDNA titre, complement levels). Most patients managed to reduce their steroid dose over the course of a year following treatment. Treatment with Obinutuzumab appeared to be reasonably safe in our patient cohort – two patients developed infections, which we might expect in patients with severe SLE receiving immunosuppression, but no patients had adverse reactions. Efficacy of Obinutuzumab in the treatment of SLE patients has been reported in a published phase II trial [1] and more recently a press release reported positive results in a phase III trial in lupus nephritis [2].

REFERENCES: [1] Furie RA, Aroca G, Cascino MD, et al. B cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis 2022;81(1):100-107.

[2] https://www.lupus.org/news/update-positive-phase-iii-clinical-trial-results-announced-for-gazyva-for-the-treatment-of

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.