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High-dose mizoribine treatment for adolescents with systemic lupus erythematosus

Authors

  • KANDAI NOZU,

    Corresponding author
    1. 1Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Department of Nephrology,2National Center for Child Health and Development, Tokyo,3Hara Genito-Urinary Hospitaland4Hyogo Children's Hospital, Kobe, Hyogo,and5Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
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  • 1 KAZUMOTO IIJIMA,

    1. 1Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Department of Nephrology,2National Center for Child Health and Development, Tokyo,3Hara Genito-Urinary Hospitaland4Hyogo Children's Hospital, Kobe, Hyogo,and5Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
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  • 2 ICHIRO KAMIOKA,

    1. 1Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Department of Nephrology,2National Center for Child Health and Development, Tokyo,3Hara Genito-Urinary Hospitaland4Hyogo Children's Hospital, Kobe, Hyogo,and5Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
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  • 1 TERUO FUJITA,

    1. 1Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Department of Nephrology,2National Center for Child Health and Development, Tokyo,3Hara Genito-Urinary Hospitaland4Hyogo Children's Hospital, Kobe, Hyogo,and5Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
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  • 1 KUNIHIKO YOSHIYA,

    1. 1Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Department of Nephrology,2National Center for Child Health and Development, Tokyo,3Hara Genito-Urinary Hospitaland4Hyogo Children's Hospital, Kobe, Hyogo,and5Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
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  • 3 RYOJIRO TANAKA,

    1. 1Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Department of Nephrology,2National Center for Child Health and Development, Tokyo,3Hara Genito-Urinary Hospitaland4Hyogo Children's Hospital, Kobe, Hyogo,and5Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
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  • 4 KOICHI NAKANISHI,

    1. 1Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Department of Nephrology,2National Center for Child Health and Development, Tokyo,3Hara Genito-Urinary Hospitaland4Hyogo Children's Hospital, Kobe, Hyogo,and5Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
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  • 5 NORISHIGE YOSHIKAWA,

    1. 1Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Department of Nephrology,2National Center for Child Health and Development, Tokyo,3Hara Genito-Urinary Hospitaland4Hyogo Children's Hospital, Kobe, Hyogo,and5Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
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  • and 5 MASAFUMI MATSUO 1

    1. 1Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Department of Nephrology,2National Center for Child Health and Development, Tokyo,3Hara Genito-Urinary Hospitaland4Hyogo Children's Hospital, Kobe, Hyogo,and5Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
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Kandai Nozu, Assistant Professor, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650–0017, Japan. Email: nozu@med.kobe-u.ac.jp

Abstract

Background: In treating pediatric patients with systemic lupus erythematosus (SLE), it is necessary to quickly attain remission to avoid sequelae in various organs and to maintain it over a long period. However, to maintain remission, the prolonged use of immunosuppressants which have various adverse effects, is often necessary in addition to steroids, and complications due to such immunosuppressants pose very important problems. A regimen of mizoribin (MZR) at 150 mg/day divided into two or three doses has been recommended, but while this regimen has been safe, its efficacy has not been satisfactory. However, MZR produces effects dose-dependently, and the dose recommended to date may have been insufficient for the treatment of children with SLE.

Methods: The authors administered oral MZR at 300 mg/day in two divided doses, which is twice the conventional dose for adults, to five adolescents with SLE. Three of these five were markedly steroid-dependent patients and two had previously been treated with steroids only. Thereafter, the authors evaluated the safety and efficacy of the regimen by following the patients for at least 7 months after the beginning of treatment.

Results: Patients 1 and 2 had been treated with prednisolone (PSL) and cyclosporine (CyA), but as the duration of CyA administration became long, it was replaced with 300 mg MZR. This transition could be accomplished smoothly. Patient 3 showed repeated recurrence during the treatment with PSL and CyA or CPM, but the symptoms could be controlled by the addition of 300 mg MZR. In patients 4 and 5, the control of symptoms with PSL alone was judged to be difficult, and concomitant administration of MZR at 300 mg was started. This resulted in a decrease in the dose of PSL. The Cmax (C2) of MZR was 1.33 μg/mL or higher in all five patients, and the efficacy of the treatment was satisfactory. Concerning side-effects, hyperuricemia was noted in two patients, but it was resolved in one of them by reducing the dose of MZR and in the other spontaneously while the treatment was continued. Temporary exacerbation of hair loss was observed in two patients, but it disappeared in both of them after a few months.

Conclusion: MZR could be administered at a high dose effectively and safely. However, monitoring of the serum uric acid level was necessary. High-dose MZR therapy showed an efficacy and safety that would warrant its application to steroid-dependent pediatric patients with SLE.

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