Safety and Efficacy of Obinutuzumab in Treating Lupus Nephritis: A Systematic Review

Background: Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE), often leading to end-stage renal disease. Despite current immunosuppressive therapies, complete renal remission remains limited. Obinutuzumab, a type II anti-CD20 monoclonal antibody, offers enhanced B-cell depletion compared to type I antibodies and may improve renal outcomes in LN. This systematic review evaluates the efficacy and safety of obinutuzumab in treating adult patients with proliferative LN. Methods: This review was registered with PROSPERO (CRD420251074418) and conducted in accordance with the PRISMA guidelines. A comprehensive search of PubMed, Cochrane, Embase, Scopus, and clinical trial registries was conducted through June 2025. Eligible studies were randomized controlled trials (RCTs) comparing obinutuzumab vs. placebo in adult patients with biopsy-confirmed active LN. Primary outcomes included complete renal response (CRR), proteinuria, and estimated glomerular filtration rate (eGFR). Secondary outcomes included immunological markers and adverse events. Data were synthesized qualitatively due to the limited available trials. Results: Two RCTs (REGENCY 2025 and NOBILITY 2022) with 396 patients met the inclusion criteria. Obinutuzumab significantly improved CRR (46.4% in REGENCY at week 76; 41% in NOBILITY at week 104) and reduced proteinuria (UPCR < 0.5 in 62% vs. 37% in controls). Improvements in eGFR, complement levels (C3 and C4), and anti-dsDNA titers were also noted. Adverse events occurred at similar rates across groups, although serious infections and infusion reactions were somewhat higher in one trial. No significant increase in mortality was observed. Conclusion: Obinutuzumab appears to be a promising therapy for proliferative LN, offering enhanced renal response and immunological benefits. Its potential for long-term renal protection and steroid-sparing effects supports further investigation through large-scale comparative trials.