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Periodically repeated rituximab administrations in children with refractory nephrotic syndrome: 2-year multicenter observational study

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Abstract

Background

Rituximab (RTX) is effective in maintaining remission in patients with nephrotic syndrome (NS), but a standard protocol of RTX administration has not been established.

Methods

This study was a 2-year multicenter observational study, in which consistent treatments and evaluations were performed. We enrolled pediatric patients with refractory NS between January 2015 and December 2015. RTX infusion was performed four times at 6-month intervals, followed by mizoribine pulse therapy with early discontinuation of calcineurin inhibitor (CNI). Primary endpoints were the relapse-free survival rate and the number of relapses after RTX administration. Secondary endpoints were changes in side effects associated with long-term steroid administration.

Results

Twenty-two patients were analyzed. The relapse-free survival rate at 1 year and 2 years was 50 and 46%, respectively. Twenty-one patients accomplished our protocol and the frequency of relapse was reduced under the discontinuation of CNI. Although two patients were diagnosed with frequent relapse and/or steroid dependency during the observation period, the frequency of relapse decreased with each rituximab dose. Statistically significant improvements in all steroid complications were observed in the final examination, but no significant improvements were observed from 1 to 2 years after RTX administration. One patient had agranulocytosis, and three patients showed electrocardiographic abnormalities.

Conclusions

Our protocol was useful and safe for refractory NS. However, RTX administration four times might have been excessive in patients who had no relapse by 1 year after the initial RTX administration. Further investigation of the most appropriate method of RTX administration is required.

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Acknowledgements

We thank all pediatricians at affiliated hospitals for data collection. Part of this work will be presented at the 55th Congress of the ERA-EDTA Congress, May 24-27, 2018, Copenhagen, Denmark. This work was supported by The Naomichi Yamada Memorial Research Foundation for Pediatric Disease (YAMAME) (T.T.)

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Authors and Affiliations

  1. Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15, West 7, Sapporo, Hokkaido, 060-8638, Japan

    Toshiyuki Takahashi, Takayuki Okamoto, Yasuyuki Sato, Takeshi Yamazaki, Asako Hayashi & Tadashi Ariga

  2. Department of Pediatrics, Obihiro Kyokai Hospital, Obihiro, Japan

    Hayato Aoyagi

  3. Department of Pediatrics, Nikko Memorial Hospital, Muroran, Japan

    Michihiko Ueno

  4. Department of Pediatrics, Oji General Hospital, Tomakomai, Japan

    Norio Kobayashi

  5. Department of Pediatrics, Obihiro Kosei Hospital, Obihiro, Japan

    Kimiaki Uetake

  6. Department of Pediatrics, Kushiro Red Cross Hospital, Kushiro, Japan

    Masanori Nakanishi

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  1. Toshiyuki Takahashi
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Correspondence to Takayuki Okamoto.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the Research Ethics Committee of Hokkaido University Hospital.

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Informed consent was obtained from the parents of all patients included in the study.

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Takahashi, T., Okamoto, T., Sato, Y. et al. Periodically repeated rituximab administrations in children with refractory nephrotic syndrome: 2-year multicenter observational study. Pediatr Nephrol 34, 87–96 (2019). https://doi.org/10.1007/s00467-018-4063-7

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  • DOI: https://doi.org/10.1007/s00467-018-4063-7

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