Abstract: FR-PO0700
Obinutuzumab for Rituximab-Refractory Membranous Nephropathy Secondary to Sjögren Syndrome
Session Information
- Glomerular Diseases: Membranous Nephropathy, FSGS, and Podocytopathies
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Yeam, Albert I., University of California Irvine School of Medicine, Irvine, California, United States
- Liu, Christopher Z., University of California Irvine School of Medicine, Irvine, California, United States
- Gee, Caroline A., University of California Irvine School of Medicine, Irvine, California, United States
- Hanna, Ramy Magdy, University of California Irvine School of Medicine, Irvine, California, United States
Introduction
Membranous nephropathy (MN) is a common cause of adult nephrotic syndrome, characterized by immune complex deposition on the subepithelial glomerular basement membrane. Rituximab, an anti-CD20 monoclonal antibody, is the first-line immunosuppressive therapy for MN, but 40% of patients fail to respond or relapse. Obinutuzumab is a humanized anti-CD20 monoclonal antibody that has shown increased antibody-dependent cellular cytotoxicity and sustained B-cell depletion compared to rituximab, posing it as a therapeutic alternative.
Case Description
We present a case of a 58-year-old female with anti-PLA2R-associated MN secondary to Sjögren’s syndrome (SS), who initially responded to rituximab. Baseline creatinine improved from 0.84 to 0.68 mg/dL and anti-PLA2R decreased from 103.5 to 3.6 RU/mL after two infusions. However, after one-year, anti-PLA2R levels increased to 22.3 RU/mL. The patient never achieved full remission, with her urine protein/creatinine ratio increasing to 6147 mg/g at two years post-treatment. The patient was switched to obinutuzumab. Anti-PLA2R levels decreased to less than 1.8 RU/mL, urine protein decreased to 849 mg/g, and creatinine remained stable at 1.0 mg/dL at four months post-induction treatment of two infusions. The patient has been in complete remission since.
Discussion
Although the patient was anti-PLA2R-positive, typically associated with primary MN, her renal biopsy revealed extraglomerular deposits involving vessels, suggesting a secondary pathology to SS. In SS, B-cell hyperactivity and elevated B-cell activating factor can lead to a high B-cell burden that may be more resistant to rituximab. Obintuzumab's glycoengineered Fc region increases antibody-dependent cellular cytotoxicity while not having to rely on complement-dependent cytotoxicity, in contrast to rituximab. Recent case reports and retrospective studies have reported remission rates of 41-94% with obinutuzumab in prior rituximab failure in primary MN. Additionally, retrospective analyses comparing the efficacy of obinutuzumab versus rituximab as primary therapies in treatment-naïve primary MN have shown comparable or greater remission with obinutuzumab. This case highlights the potential efficacy of obinutuzumab in achieving remission of MN secondary to SS, particularly following relapse with rituximab therapy, supporting its consideration as an alternative therapeutic in refractory cases.