Matias Trillini, Valentina Portalupi, Alessia Gennarini, Livia Surdi, Annachiara Currado, Maddalena Marasà, Manuel Alfredo Podestà, Alessandro Villa, Tobia Peracchi, Diego Fidone, Nadia Rubis, Olimpia Diadei, Chiara Guarinoni, Federica Casiraghi, Marta Todeschini, Daniela Cugini, Fabiola Carrara, Davide Martinetti, Paola Rizzo, Giuseppe Remuzzi, Piero Ruggenenti
Introduction: Approximately 30% of patients with primary membranous nephropathy (MN) and persistent nephrotic syndrome (NS) fail rituximab therapy through mechanisms that could be overcome by obinutuzumab. Methods: In this prospective, single-arm, single-center, open-label trial, 20 consenting adults with MN and rituximab-resistant NS received three 1000 mg obinutuzumab infusions at the Bergamo Nephrology Unit (Italy) between March 2022 and February 2024 and were monitored for ≤ 12 months. The primary outcome was a composite end point of normo-albuminemia and complete (proteinuria < 0.3 g/d) or partial (proteinuria < 3.5 g/d with ≥ 50% reduction from baseline) NS remission at 12-month follow-up. Twenty-four-hour proteinuria and glomerular filtration rate (GFR) were evaluated at baseline and at 3, 6, 9, 12, 18, and 24 months posttreatment. Results: R antibodies and proteinuria, or relapses. Treatment was safe and well-tolerated. Conclusion: Obinutuzumab treatment is extremely effective and safe in patients with MN and rituximab-resistant NS and can achieve persistent remission in this population.