Obinutuzumab is Effective as an Initial Treatment for PLA2R-Associated Primary Membranous Nephropathy: A Retrospective, Single-Center Trial

Membranous nephropathy (MN) can cause nephrotic syndrome. B cells contribute to MN, but available treatments are often inadequate. We addressed this treatment gap by analyzing the effect of obinutuzumab in patients with primary MN (PMN). Forty-seven PMN patients were followed for six months, with 25 receiving obinutuzumab and 22 (control) receiving rituximab. Treatment response was assessed by 24-h urine total protein (24-h UTP), serum albumin (ALB), and other indicators. Immunologic remission was assessed by measurement of anti-phospholipase A2 receptor autoantibodies (PLA2R autoAbs). Relative to baseline, the obinutuzumab group had significant decreases of PLA2R autoAbs (83.40 [55.90-344.36] vs 0.41 [0.17-1.20] RU/mL), 24-h UTP (8.90 [7.15-13.80) vs 1.82 [1.12-3.43] g/day), and B cells (312.61 [202.00-406.12) vs 0 [0-0] cells/μL), and a significant increase of serum ALB (25.90 [20.85-28.70] vs 42 [39.7-45.3] g/L) after six months. Nineteen of the evaluable patients (76% [55-91%]) achieved immunological remission at three months, 20 (80% [60-93%] achieved immunological remission at six months, and 16 (64% [42-83%] achieved partial response (PR) at three-months. After six-months, no patients achieved complete remission, but 19 (76% [55-91%]) achieved PR. Before the second dose of obinutuzumab, the CD19+ B cell count in 20 patients (80%) [60%-93%] was less than 1 cell/μL, and 18 patients had counts of 0 cells/μL. At the 6-month follow-up, the rituximab and obinutuzumab groups had no significant differences in immunological remission (80% vs 64%; OR: 2.29 [0.62-8.47]; P=0.211) or clinical remission (76% vs 59%; OR: 2.19 [0.63-7.66]; P=0.215]. No patients experienced serious adverse events. This retrospective analysis suggests that obinutuzumab may have potential as an initial therapeutic option for patients with PMN, although larger controlled studies are needed for confirmation.