Efficacy of Rituximab as Adjunctive Therapy to Immunosuppressive Agents in Adult Primary Focal Segmental...

Primary focal segmental glomerulosclerosis (FSGS) is a rare, likely immune-related disease. Rituximab (RTX) may help manage it, but existing adult data are limited and mainly based on case reports or case series. We aimed to evaluate RTX treatment outcomes in a large, multicenter adult cohort.

This was a retrospective study of 160 patients with primary FSGS treated with RTX as adjunctive therapy to standard immunosuppressive agents between March 2015 and June 2023, that evaluated treatment responses at 3, 6, and 12 months, followed by an extended 24-month follow-up to assess long-term outcomes. Treatment outcomes included complete response (CR), partial response (PR), or no response. Treatment-related adverse effects and relapse-free survival (RFS) were evaluated at each visit. Patients undergoing RTX retreatment and those monitored for an extended 24-month period were analyzed independently.

Response rates at 3, 6, and 12 months were 57%, 71%, and 74%, respectively. Twelve-month RTX response was positively associated with lower baseline 24-hour proteinuria (odds ratio [OR] = 0.49, P = 0.043), steroid dependency (OR = 20.59, P = 0.002), and not otherwise specified (NOS) variant (OR = 234.19, P = 0.004), whereas it was negatively associated with calcineurin inhibitor (CNI) resistance (OR = 0.03, P = 0.01), treatment-related adverse effects (OR = 0.02, P = 0.003), and CD20+ B-cell repopulation at 6 months (OR = 0.08, P = 0.02). Thirty adverse effects occurred in 16 patients. Twelve-month responders had significantly longer RFS (mean: 32.8 months, 83.1% relapse-free) compared with nonresponders (median: 9 months, 16.7% relapse-free; P < 0.001). RTX retreatment was administered to 44 patients, with 2 achieving CR and 18 achieving PR. During long-term follow-up, 82 of 118 responders at 12 months maintained a sustained response, whereas 20 relapsed. Twenty-two of 42 nonresponders at 12 months had persistent disease despite RTX retreatment, whereas 10 achieved PR.

RTX shows promise in treating primary FSGS, particularly in steroid-dependent patients, those with less severe nephrotic syndrome, and previous responders. RTX offers durable responses for most patients, but long-term management remains challenging in those who relapse and need retreatment.