Impact of FCGR2A and FCGR3A Gene Variants on the Response to Rituximab in Patients With Glomerular Diseases

Rituximab is an anti-CD20 monoclonal antibody used in autoimmune diseases, including glomerular diseases. The FCGR2A (rs1801274) and FCGR3A (rs396991) variants have been suggested to affect rituximab efficacy; this study evaluates their impact on rituximab efficacy in glomerular diseases. A clinical trial was performed including adults with glomerular diseases who required rituximab (NEFRTX; EudraCT: 2020-000484-23). Patients received 1.0 g or 0.5 g of rituximab on day 1 (± day 14); biochemical parameters and rituximab concentration were measured, and FCGR2A and FCGR3A variants were characterized. Clinical outcome was evaluated at 6 and 12 months. 30 patients were included. FCGR2A (rs1801274) and FCGR3A (rs396991) variants did not show an effect on clinical response to rituximab. When the effect of the variant was corrected by rituximab exposure, the expression of the FCGR2A rs1801274-A allele vs. no expression was related to a poorer response at month 6 (odds ratio 0.034; 95% confidence interval 0.002-0.725; p = 0.030); this effect was not seen for FCGR3A. Additional studies involving larger cohorts are warranted to validate these findings.