First-line and Second-line Therapy of Zuberitamab in Idiopathic Membranous Nephropathy: A Single-center Retrospective...

Idiopathic membranous nephropathy (IMN) is a major cause of nephrotic syndrome. Although rituximab has improved outcomes, resistance or intolerance occurs in a subset of patients. Zuberitamab, a chimeric anti-CD20 immunoglobulin G1 monoclonal antibody, may offer an alternative therapeutic option. This study aimed to evaluate the effectiveness and safety of zuberitamab in patients with phospholipase A2 receptor (PLA2R)-associated IMN.

Single-center, retrospective observational cohort study.

Sixty patients with biopsy-proven or serologically diagnosed PLA2R-associated IMN were treated with zuberitamab at Henan Provincial People's Hospital between July 2023 and June 2024. Thirty-five received zuberitamab as first-line therapy; 25 received it as second-line therapy following prior immunosuppressive treatment.

Zuberitamab infusions administered in 2-3 doses over several months, guided by B-cell kinetics.

The primary outcome was complete or partial remission of proteinuria at 3 and 6 months. Secondary outcomes included changes in serum albumin, serum creatinine, estimated glomerular filtration rate, CD19+ B cells, and anti-PLA2R antibody titers.

At month 3, 80% (48/60) of patients achieved remission (5 complete and 43 partial). By month 6, 13 patients achieved complete remission (11 first line and 2 second line; P = 0.03), and 35 achieved partial remission. Serum albumin levels improved, whereas proteinuria and creatinine levels declined in both groups. At 6 months, PLA2R antibody < 2 RU/mL was seen in 90.9% (30/33) of first-line and 81.0% (17/21) of second-line patients (P = 0.29). No serious adverse events were observed.

Single-center, retrospective design; short follow-up; no direct comparator group; incomplete biomarker data owing to testing limitations.

Zuberitamab was associated with favorable clinical and immunologic responses in patients with IMN, including those previously treated with rituximab. These findings support its potential role as a therapeutic option, warranting further validation in prospective studies.