Obinutuzumab in Rituximab-resistant and recurrent membranous nephropathy: a case-series

BACKGROUND: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults, with high risk of progression to end-stage kidney disease when untreated. Rituximab is commonly used in its treatment however many patients do not respond. Obinutuzumab is a novel anti-CD20 monoclonal antibody for which there is increasing observational evidence in treatment-resistant membranous nephropathy. The majority of evidence for its use relates to anti-phospholipase A2 receptor-(PLA2R) associated membranous nephropathy. METHODS: This was a single-centre case-series of all patients at a tertiary nephrology centre in Melbourne, Australia, treated with Obinutuzumab for membranous nephropathy, between January 2023 and June 2024. All patients who received Obinutuzumab were included in this case-series, irrespective of PLA2R status. RESULTS: Out of 5 patients with treatment-resistant membranous nephropathy, 3 had PLA2R-associated membranous nephropathy which had previously been refractory to, or relapsed on Rituximab therapy. All 3 patients with PLA2R-positive membranous nephropathy achieved complete immunological and clinical remission after receiving Obinutuzumab. The case of secondary PLA2R-negative membranous nephropathy only achieved partial remission after Obinutuzumab before unexpectedly dying from another cause. The case of recurrent PLA2R-associated membranous nephropathy in a renal allograft did not respond to Obinutuzumab. CONCLUSION: This case-series supports the existing evidence in favour of Obinutuzumab for treatment-resistant PLA2R-associated membranous nephropathy. To our knowledge it is the first reported use of Obinutuzumab in sarcoidosis-associated membranous nephropathy.