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Predictive factors of long-term disease remission after rituximab administration in patients with childhood-onset complicated steroid-dependent nephrotic syndrome: a single-center retrospective study

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Abstract

Background

Despite the fact that rituximab (RTX)-associated adverse events may be relatively frequent in younger patients, recent studies have reported RTX as a suitable first-line steroid-sparing agent for maintaining remission in children with steroid-dependent nephrotic syndrome (SDNS). However, the impact of age at RTX initiation on the long-term outcome remains unknown in this cohort.

Methods

We retrospectively reviewed the clinical course of 61 patients with complicated SDNS who received a single dose of RTX (375 mg/m2) followed by maintenance immunosuppressive agents (IS) from January 2008 to March 2021. In patients who achieved > 12 months of prednisolone-free remission, IS tapering within 6 months was tried to achieve. The primary endpoint was the probability of achieving long-term treatment-free remission at the last follow-up.

Results

After RTX initiation, 52 patients (85.2%) relapsed after a median of 665 days, and 44 patients (72.1%) received additional RTX doses (total, 226 infusions). At the last follow-up (median observation period, 8.3 years; median age, 18.3 years), 16 patients (26.2%) achieved long-term remission. Multivariate analysis showed that older age at RTX initiation was the independent predictive factor for achieving long-term remission (odds ratio, 1.25; p < 0.05). The proportion of those who achieved long-term remission was significantly higher in patients aged ≥ 13.5 years than in those aged < 13.5 years at RTX initiation (52.6 vs 14.3%, p < 0.05). Persistent severe hypogammaglobulinemia did not develop in older children (≥ 13.5 years) at RTX initiation.

Conclusion

For older children with complicated SDNS, RTX appeared to be a suitable disease-modifying therapy without persistent adverse events.

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Data availability

The datasets of the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank MARUZEN-YUSHODO Co., Ltd. for the English language editing.

Funding

SF has received Grants-in-Aid for research of Saitama Children's Medical Center (2021-B-3).

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Authors and Affiliations

  1. Division of Nephrology, Saitama Children’s Medical Center, 1-2 Shintoshin, Chuo-Ku, Saitama, 330-8777, Japan

    Rie Ohyama, Shuichiro Fujinaga & Koji Sakuraya

  2. Department of Pediatrics, Yokohama City University Hospital, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan

    Rie Ohyama

  3. Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan

    Daishi Hirano

  4. Department of Pediatrics, Yokohama City University, Graduate School of Medicine, Yokohama, Kanagawa, Japan

    Shuichi Ito

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  1. Rie Ohyama
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  5. Shuichi Ito
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Contributions

RO and SF designed the study, drafted the manuscript, were responsible for the data integrity and analysis results. DH provided statistical support. All authors critically reviewed and approved the final manuscript.

Corresponding author

Correspondence to Shuichiro Fujinaga.

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Conflict of interest

Ito received grants from Zenyaku Kogyo Co., Ltd. and lectures fees from Chugai Pharmaceutical Co., Ltd.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards set by the ethics committee of Saitama Children’s Medical Center in which the study was conducted (approval number, 2022–03-010) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

The Institutional Review Board waived the requirement for informed consent due to the retrospective nature of this study.

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Ohyama, R., Fujinaga, S., Sakuraya, K. et al. Predictive factors of long-term disease remission after rituximab administration in patients with childhood-onset complicated steroid-dependent nephrotic syndrome: a single-center retrospective study. Clin Exp Nephrol 27, 865–872 (2023). https://doi.org/10.1007/s10157-023-02374-6

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  • DOI: https://doi.org/10.1007/s10157-023-02374-6

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