[Efficacy and safety of obinutuzumab in children with refractory nephrotic syndrome]

Objective: To evaluate the efficacy and safety of obinutuzumab (OBZ) in children with refractory nephrotic syndrome (RNS) who have a poor response to rituximab (RTX) therapy. Methods: This retrospective cohort study enrolled children with primary RNS who received OBZ because of poor response to RTX at the Children's Medical Center of Peking University First Hospital from July 2024 to December 2025. For each patient, outcomes during the OBZ treatment phase were compared with those during their preceding RTX treatment phase. Comparative parameters included duration of sustained B-cell depletion, duration of urinary protein remission, tapering of glucocorticoids and immunosuppressants, relapse frequency, and adverse events. Paired t-test, Wilcoxon signed-rank test, Mann-Whitney U test, χ² test and Fisher's exact test were adopted for statistical analysis according to the data type and distribution characteristics. Results: Thirteen children (10 males, 3 females) were enrolled. The age at disease onset was (47±13) months, and the age at first OBZ administration was (121±35) months. There were 3 cases of steroid-resistant and 10 cases of steroid-sensitive but frequently relapsing nephrotic syndrome. Compared with the RTX phase, the OBZ phase was associated with significantly longer durations of sustained B-cell depletion, sustained urinary protein remission, and annual glucocorticoid and calcineurin inhibitor (CNI) withdrawal (all P<0.05). The annual relapse frequency was significantly lower during OBZ treatment than during RTX treatment (0 (0, 0.3) vs. 1.9 (1.4, 2.6), Z=3.06, P=0.002). Regarding safety, 2 children developed mild transient infusion reactions (gastrointestinal discomfort and elevated blood pressure), which resolved with reduced infusion rate; 1 child discontinued OBZ due to concurrent pneumonia and otitis media; and 7 developed asymptomatic hypogammaglobulinemia. No severe adverse events, such as severe neutropenia, thrombocytopenia or organ dysfunction, were documented. Conclusions: For children with RNS who experience short B-cell depletion duration and frequent relapse after RTX therapy, OBZ provides more durable B-cell depletion, effectively prolongs urinary protein remission, reduces relapse risk, and facilitates safer glucocorticoid tapering. These findings suggest that OBZ may serve as a viable alternative therapeutic option for this specific pediatric population.