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Background <p>Rituximab (RTX), a chimeric human-murine monoclonal antibody, is an established therapeutic agent for children with frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS). However, RTX-induced immunogenicity, characterized by the production of anti-rituximab antibodies (ARA), might compromise the therapeutic efficacy of RTX and alter its safety profile. To date, the impact of ARA on RTX pharmacokinetics, clinical efficacy, and safety in this specific pediatric population remains not fully elucidated.</p> Methods <p>This retrospective study included 33 children with FRNS/SDNS categorized by ARA status (16 positive and 17 negative). We compared RTX concentrations, CD19⁺ B-cell depletion kinetics (Kaplan–Meier/Cox models), clinical outcomes (relapses, UACR), and safety between groups. The associations between ARA titers, drug levels, and therapeutic efficacy were analyzed using Spearman’s correlation and multivariate linear regression.</p> Results <p>The ARA positivity rate was 48.5%. ARA-positive patients exhibited significantly lower median RTX concentrations than ARA-negative patients (20.48 vs. 52.85&#xa0;μg/mL, <i>P</i> &lt; 0.001), with RTX levels negatively correlating with ARA titers (ρ =  − 0.875, <i>P</i> &lt; 0.001). Multivariate regression identified ARA positivity as an independent predictor of reduced RTX exposure (β =  − 26.89, <i>P</i> &lt; 0.001). Furthermore, the ARA-positive group showed significantly shorter B-cell depletion (58.5 vs. 163&#xa0;days, <i>P</i> &lt; 0.001; HR = 6.11), more frequent relapses at 12&#xa0;months (<i>P</i> = 0.004), and higher cumulative RTX treatments (<i>P</i> = 0.043). No significant differences in safety profiles were observed (<i>P</i> &gt; 0.05).</p> Conclusion <p>ARA positivity is common in pediatric FRNS/SDNS. The presence of ARA is associated with lower RTX serum levels, shortened B-cell depletion duration, and increased risk of relapse, but it does not significantly impact treatment safety. Routine monitoring of ARA status should be considered to guide individualized RTX therapy and optimize outcomes.</p> Graphical Abstract <p></p>

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The impact of anti-rituximab antibodies on rituximab efficacy in children with frequently relapsing or steroid-dependent nephrotic syndrome

  • 期刊论文

  • 发表日期：

    2026年7月22日

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  • Daojing Wang,
  • Wenjing Kang,
  • Kai Chen,
  • Na Li,
  • Huihui Yang,
  • Juanjuan Ding,
  • Xiaowen Wang

摘要

Background

Rituximab (RTX), a chimeric human-murine monoclonal antibody, is an established therapeutic agent for children with frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS). However, RTX-induced immunogenicity, characterized by the production of anti-rituximab antibodies (ARA), might compromise the therapeutic efficacy of RTX and alter its safety profile. To date, the impact of ARA on RTX pharmacokinetics, clinical efficacy, and safety in this specific pediatric population remains not fully elucidated.

Methods

This retrospective study included 33 children with FRNS/SDNS categorized by ARA status (16 positive and 17 negative). We compared RTX concentrations, CD19⁺ B-cell depletion kinetics (Kaplan–Meier/Cox models), clinical outcomes (relapses, UACR), and safety between groups. The associations between ARA titers, drug levels, and therapeutic efficacy were analyzed using Spearman’s correlation and multivariate linear regression.

Results

The ARA positivity rate was 48.5%. ARA-positive patients exhibited significantly lower median RTX concentrations than ARA-negative patients (20.48 vs. 52.85 μg/mL, P < 0.001), with RTX levels negatively correlating with ARA titers (ρ =  − 0.875, P < 0.001). Multivariate regression identified ARA positivity as an independent predictor of reduced RTX exposure (β =  − 26.89, P < 0.001). Furthermore, the ARA-positive group showed significantly shorter B-cell depletion (58.5 vs. 163 days, P < 0.001; HR = 6.11), more frequent relapses at 12 months (P = 0.004), and higher cumulative RTX treatments (P = 0.043). No significant differences in safety profiles were observed (P > 0.05).

Conclusion

ARA positivity is common in pediatric FRNS/SDNS. The presence of ARA is associated with lower RTX serum levels, shortened B-cell depletion duration, and increased risk of relapse, but it does not significantly impact treatment safety. Routine monitoring of ARA status should be considered to guide individualized RTX therapy and optimize outcomes.

Graphical Abstract