Prospective Cohort Study of Felzartamab in Rituximab-Resistant Primary Membranous Nephropathy

作者：Matias Trillini, F. Casiraghi, A. Gennarini, V. Portalupi, M. Marasà, M. A. Podestà, S. Prandini, Silvia Nozza, M. Todeschini, F. Pecoraro, M. Mister, Fabiola Carrara, N. Stucchi, T. Peracchi, Diego Fidone, A. Villa, N. Rubis, Olimpia Diadei, D. Martinetti, G. Remuzzi, P. Ruggenenti · 发表于：Kidney International Reports · 年份：2026 · DOI：10.1016/j.ekir.2026.106468 · 被引用次数：1 · 研究领域：Medicine

Introduction Approximately 30% of patients with primary membranous nephropathy (MN) and nephrotic syndrome (NS) fail rituximab treatment through mechanisms that could be overcome by the human IgG1 monoclonal anti-CD38 antibody, felzartamab. Methods In this prospective, single-arm, single-center, open-label trial, 10 consenting Caucasian adult patients with MN, rituximab-resistant NS, and estimated glomerular filtration rate (GFR) > 30 ml/min per 1.73 m2 received a 5-month, 9-dose course of 16 mg/kg felzartamab infusions at the Nephrology Unit of Bergamo Hospital, Italy between November 9, 2021 and February 1, 2023 and were followed up with for 24 months. Clinical and laboratory parameters were evaluated at baseline, 1, 2, 5, 6, 9, 18, and 24 months, whereas GFR as well as albumin and IgG fractional clearances were measured at baseline and at 6, 9, 12, 18, and 24 months posttreatment. The primary outcome was 24-hour proteinuria (median of 3 consecutive measurements) at 12 months. Results Twelve-month 24-hour proteinuria was similar to baseline. Linear-mixed model analyses showed no significant time-dependent changes in 24-hour proteinuria and albuminuria; serum total-protein, albumin, creatinine and lipid levels, GFR and albumin fractional clearances. Circulating anti–phospholipase A2 receptor (PLA2R) antibodies transiently decreased but were never depleted. All considered Igs transiently decreased up to month 12, and recovered to baseline thereafter. Felzartamab deeply and pe...