Obinutuzumab Induced Decreases of PLA2R Antibodies in Membranous Nephropathy: a Pilot Study
Trial Parameters
Brief Summary
Objective: To assess the disappearance rate (half-life) of anti-PLA2R antibodies in high-risk primary membranous nephropathy (pMN) patients treated with obinutuzumab (OBI), and to evaluate immunological and clinical remission, adverse events, and quality of life. Design: Open-label, single-center, prospective pilot intervention study conducted at Radboud University Medical Center. Population: 20 adult patients with high-risk PMN, defined by proteinuria ≥3.5 g/24h despite 6 months of supportive treatment with ACE inhibitors or ARBs. Intervention: OBI 1000 mg on days 1 and 15, with two additional infusions after 6 months if anti-PLA2R antibody levels remain positive and proteinuria exceeds 2 g/24h. Follow-up: Patients were monitored at baseline, and at weeks 1, 2, 4, 8, 12, 24, 37, and 52.
Eligibility Criteria
Inclusion Criteria: * Age ≥ 18 years. * Diagnosis of PMN, confirmed by: 1. Kidney biopsy or 2. Positive serum PLA2Rab test either by IFT and/or ELISA) * Serum PLA2Rab titer \> 80 RU/ml * Proteinuria ≥ 3.5 g/24h despite supportive treatment for at least 6 months with a maximally tolerated and stable dose of ACE-i or ARB. * Serum albumin \< 30 g/l measured by BCP assay. * eGFR ≥ 30 ml/min/1.73m2. * Treatment with immunosuppression is warranted, as determined by the treating physician. Exclusion Criteria: * Secondary MN (e.g., hepatitis B or C infection, human immunodeficiency virus infection, active infection, systemic lupus erythematosus, sarcoidosis, IgG4-related, drug-induced, malignancy). * RTX within 12 months prior to inclusion. * CNI within 2 months prior to inclusion. * Treatment with other immunosuppressive drugs within 6 months prior to inclusion. * Proteinuria must not have decreased by \> 50% over 6 months whilst taking ACEi/ARB. * Life-threatening nephrotic syndrome resistan