Obinutuzumab after anti-rituximab antibody-associated treatment failure in membranous nephropathy: a case report

Rituximab is an established therapy for primary membranous nephropathy, but anti-rituximab antibodies (ARA) have been associated with rituximab treatment failure. We report a 66-year-old woman with PLA2R-positive membranous nephropathy who developed ARA positivity and clinical features consistent with rituximab treatment failure, including B-cell reconstitution, undetectable serum rituximab levels, and worsening proteinuria despite declining anti-PLA2R antibody titers. Kidney biopsy confirmed stage III membranous nephropathy. She was subsequently treated with the humanized type II anti-CD20 antibody obinutuzumab, which induced complete depletion of circulating B cells, achieved therapeutic serum concentration, follow by both immunological and clinical remission within 8.5 months, despite persistent ARA positivity. This case suggests that obinutuzumab may be an effective rescue option after rituximab failure associated with ARA and underscores the importance of integrating therapeutic drug monitoring, ARA detection, and B-cell kinetics assessment in the management of refractory membranous nephropathy.