Efficacy of rituximab in refractory focal segmental glomerulosclerosis

Objective: Refractory focal segmental glomerulosclerosis (FSGS) poses significant therapeutic challenges under conventional immunosuppressants. Although rituximab (RTX), an anti-CD20 monoclonal antibody, has demonstrated efficacy in nephrotic syndrome, its real-world effectiveness in adults with refractory FSGS remains unproven. Study Design: We retrospectively included 34 adults with biopsy-proven FSGS who remained refractory, defined by persistent proteinuria >3.5 g/day despite ≥4 months of corticosteroids/calcineurin inhibitors. Patients were grouped into either RTX combining with prednisone (RTX group, n = 16) or conventional non-RTX regimens (Conv group, n = 18). Rituximab was dosed to achieve peripheral B-cell depletion (CD19⁺ cell = 0/μL). Endpoints comprised complete remission (CR), overall response, relapse in initial responders, and relapse-free survival. Results: The patients were 44.4±21.8 years old, with a median follow-up duration of 18.0 (10.6, 41.1) months. The baseline characteristics were comparable between groups, except that RTX group had a longer disease duration than Conv group (median 10.7 vs. 4.0 months, p=0.046). The CR rate was 62.5% in RTX group and 33.3% in Conv group (p=0.168), while the overall response rate was 75.0% in RTX group and 50.0% in Conv-group (p=0.172). In patients who achieved initial overall response, RTX group had a lower relapse rate than Conv group (25.0% vs. 77.8%, p=0.030), and had a prolonged relapse-free survival (log-rank χ²=3.827, p=0.050). There were 3 patients in RTX group relapsed, who achieved CR after repeat RTX therapy. No severe infusion reactions or opportunistic infections were observed in RTX group. Conclusions: RTX combining with prednisone was comparable in inducing remission for refractory FSGS patients and better in relapse prevention than conventional therapy. While heterogeneity exists, RTX may be a valuable therapeutic strategy for maintaining long-term disease control in responsive patients.