obinutuzumab with mycophenolate mofetil for treating lupus nephritis

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unclear etiology that affects multiple vital organs, which is characterized by a relapsing-remitting course and is associated with significant morbidity and mortality:

• B cells play a central role in the pathogenesis of SLE
• CD20, a transmembrane protein broadly expressed on B cells at various developmental stages, is a key therapeutic target for B cell depletion

Obinutuzumab is a glycoengineered, humanized type II anti-CD20 IgG1 monoclonal antibody approved for the treatment of hematologic malignancies such as chronic lymphocytic leukemia and follicular lymphoma (1):

• targets a distinct epitope on CD20 and induces more potent direct cell death, antibody-dependent cellular cytotoxicity (ADCC), and phagocytosis, while CD20 internalisation is reduced
• a 48 week real-world study showed that obinutuzumab showed favorable efficacy and safety in SLE, including severe/refractory manifestations

A further study showed that, among adults with active lupus nephritis, obinutuzumab plus standard therapy was more efficacious than standard therapy alone in providing a complete renal response (2).

About 60% of people with systemic lupus erythematosus develop lupus nephritis (3).

NICE state (3):

• obinutuzumab plus mycophenolate mofetil can be used, within its marketing authorisation, as an option to treat active class 3 or 4 (with or without class 5) lupus nephritis in adults

The NICE committee noted that (3)

• “..Usual treatment for lupus nephritis includes mycophenolate mofetil alone or mycophenolate mofetil plus belimumab, rituximab or voclosporin (all given with corticosteroids)…Clinical trial evidence shows that obinutuzumab plus mycophenolate mofetil increases the chance of complete renal response and increases the time to renal flare compared with mycophenolate mofetil alone. Obinutuzumab plus mycophenolate mofetil has not been directly compared in a clinical trial with belimumab, rituximab or voclosporin. But indirect comparisons suggest it is likely to work as well as these..”

Reference:

1. Wu C et al. Obinutuzumab in systemic lupus erythematosus: a real-world experience. Front Immunol. 2025 Nov 19;16:1702550. doi: 10.3389/fimmu.2025.1702550. Erratum in: Front Immunol. 2025 Dec 16;16:1764419.
2. Furie RA et al; REGENCY Trial Investigators. Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis. N Engl J Med. 2025 Apr 17;392(15):1471-1483.
3. NICE (February 2026). Obinutuzumab with mycophenolate mofetil for treating lupus nephritis.