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

Background: 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). Methods: 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). Results: 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/ mu L), 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/mu L, and 18 patients had counts of 0 cells/mu L. 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. Conclusion: 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.