Rituximab Resistance in Glomerular Diseases: A GlomCon Mini Review

Abstract

Resistance to rituximab B-cell depletion therapy is a clinically pertinent adverse sequela, which can have significant implications for the treatment of immune-mediated glomerular diseases. The true incidence of rituximab resistance remains unknown, however, it is an increasingly recognized treatment complication. Resistance typically presents with suboptimal treatment response, rapid B-cell reconstitution, and a relapsing disease course. While the diverse mechanisms resulting in rituximab resistance are ongoing topics of research, both primary and secondary mechanisms have been identified as key catalysts.The emergence of human anti-chimeric antibodies (HACA) is a major cause of secondary resistance to rituximab therapy and typically appears following repeated drug exposure. Frequently, HACA develop in the setting of underlying autoimmune disease and contribute to poor B-cell depletion, reduced rituximab therapeutic efficacy, and enhanced drug clearance.The clinical challenge of rituximab resistance necessitates heightened awareness among clinicians. Screening for HACA should be considered in individuals with poor clinical response to rituximab, more rapid B-cell reconstitution, and relapsing disease. Detection of HACA may guide treatment alterations, including addition of further immunosuppressive therapy and transitioning to a humanized B-cell depleting monoclonal antibody.