Obinutuzumab as Initial or Second-Line Therapy in Patients With Primary Membranous Nephropathy

B-cell lymphocytes have been demonstrated to play a key role in the pathogenesis underlying membranous nephropathy (MN). The aim of this study was to evaluate the therapeutic efficacy and safety of Obinutuzumab, a glycoengineered type II anti-CD20 monoclonal antibody in individuals with MN.

We retrospectively analyzed data from 59 consecutive patients with primary MN who provided consent to receive Obinutuzumab and were followed for at least 6 months. The primary outcomes were complete (proteinuria <0.3 g/d) or partial (proteinuria <3.5 g/d with ≥ 50% reduction) remission of proteinuria.

Twenty patients received Obinutuzumab as initial therapy, and 39 patients were previously treated with at least 1 immunosuppressant (second-line therapy). Fifty patients (84.7%) achieved complete remission (CR) or partial remission (PR) of proteinuria during the median follow-up of 9.4 months. The likelihood of remission was significantly higher when Obinutuzumab was used as initial therapy than as second-line therapy after adjusting for the baseline estimated glomerular filtration rate (eGFR), 24-hour urinary protein levels, and anti-phospholipase A₂ receptor (PLA₂R) status (adjusted hazard ratio [HR], 4.5; 95% confidence interval [CI]: 2.1-9.5, P < 0.001). Circulating CD19⁺ B-cell count decreased to <5 cells/μl in all patients within 2 weeks after infusion. Serum anti-PLA₂R concentrations decreased to <14 relative units (RU)/ml in 43 of 48 patients with PLA₂R-related MN. After Obinutuzumab administration, a significant reduction in 24-hour urine protein and increase in serum albumin were observed. No serious adverse events were observed.

Obinutuzumab may represent a promising and well-tolerated therapeutic option for individuals with primary MN. The potential of Obinutuzumab was highlighted as an initial therapy for primary MN.