Switching Beyond Rituximab in Primary Glomerular Diseases: A Systematic Review of Within-Patient Efficacy and Safety of Non-Rituximab Anti-CD20 Antibodies

Background/Objectives: Rituximab is widely used in primary glomerular diseases, but treatment may fail for several reasons, including primary non-response, incomplete response, relapse, intolerance or anti-rituximab antibodies. We assessed within-patient efficacy and safety after switching to another anti-CD20 antibody, considering the reason for switching. Methods: PubMed and Scopus were searched from inception to 15 May 2026 without language restrictions. Eligible reports included adults with primary glomerular disease treated with a non-rituximab anti-CD20 antibody after rituximab and reporting within-patient outcomes. Risk of bias was assessed with design-specific JBI tools and certainty with GRADE. Heterogeneity precluded meta-analysis, and findings were synthesized narratively. Results: A total of 309 patients were included across 43 studies: 283 had membranous nephropathy (MN), 18 had minimal change disease (MCD), 6 had focal segmental glomerulosclerosis (FSGS), and 2 had IgA nephropathy (IgAN). Obinutuzumab was the principal drug used, and the main reasons for switching were primary non-response, with immunization, relapse, or intolerance occurring less frequently. In MN, among the 262 patients with available response data, 217 achieved complete or partial remission, and relapse was rare. For MCD, 17 of 18 patients with active disease attained remission, and only one relapsed during follow-up. On the other hand, five out of the six FSGS patients responded, but three of them relapsed. The two patients with IgAN achieved either complete or partial remission. Notably, these results may not apply to conventional IgAN, since one biopsy showed contextually MCD and the other was proliferative and crescentic. Infusion-related reactions were the most frequent adverse events and were generally mild, while infections were the main issue during the follow-up. Evidence certainty for all outcomes was very low. Conclusions: Switching to a non-rituximab anti-CD20 antibody may be a feasible rescue strategy, most convincingly after intolerance, rituximab immunization, or relapse. The uncontrolled, very-low-certainty evidence precludes firm recommendations, and controlled studies are warranted.