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

Abstract

IntroductionB-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. MethodsWe retrospectively analysed 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. ResultsTwenty patients received obinutuzumab as initial therapy and 39 patients were previously treated with at least one immunosuppressant (second-line therapy). Fifty patients (84.7%) achieved complete or partial remission 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, 24-hour urinary protein levels, and anti-phospholipase A2 receptor (PLA2R) status (adjusted HR, 4.5; 95%CI 2.1 to 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/mL in 43 out of 48 patients with PLA2R–related MN. Following Obinutuzumab administration, a significant reduction in 24-hour urine protein and increase in serum albumin were observed. No serious adverse events were observed. ConclusionObinutuzumab 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.