Anti-rituximab antibodies: implications for clinical outcomes and safety in pediatric idiopathic nephrotic syndrome.

BACKGROUND: Rituximab (RTX) has been proven effective in the treatment of idiopathic nephrotic syndrome (INS). The development of anti-rituximab antibodies (ARA) may compromise its efficacy and safety. However, the incidence and clinical relevance of ARA in pediatric INS remain incompletely defined. METHODS: This retrospective study involved 90 pediatric patients with INS who were treated with RTX at a dose of 375 mg/m2 at Jinling Hospital, Affiliated Hospital of Medical School of Nanjing University, China, between March 2024 and May 2025. ARA were detected using a paramagnetic particle chemiluminescence immunoassay. RESULTS: ARA were detected in 30 of 90 patients (33.3%). The incidence of ARA positivity increased progressively with subsequent RTX infusions, rising markedly after the third infusion. ARA-positive patients had a significantly higher relapse rate compared with ARA-negative patients (83.3% vs. 25.0%, p < 0.001), higher CD20⁺ B-cell counts at 3 and 6 months (p < 0.005), and an increased risk of infusion-related reactions (IRR) during multiple RTX infusions (p = 0.019). Multivariate analyses identified younger age at first RTX administration, a higher number of RTX infusions, and occurrence of multiple IRR as independent risk factors for ARA positivity. CONCLUSION: ARA are associated with impaired B-cell depletion and higher relapse rates. Monitoring ARA may help identify patients at risk of treatment failure and guide individualized therapeutic strategies.