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Efficacy of weekly mizoribine pulse therapy in refractory lupus nephritis

  • Original Article
  • Published:
Modern Rheumatology

Abstract

Objective

We investigated the efficacy of a high-dose intermittent dosing treatment method (weekly mizoribine pulse therapy) conceived in the hope of achieving better efficacy by increasing the peak blood levels of mizoribine in patients with refractory lupus nephritis.

Methods

Seventeen patients with lupus nephritis who had been resistant to corticosteroid and immunosuppressant therapy received weekly mizoribine pulse therapy. Mizoribine (350 mg) was administered three times at 12 h intervals over 2 consecutive days (700 mg for day 1 and 350 mg for day 2), followed by a washout period from day 3 to day 7.

Results

This therapeutic strategy enabled the peak blood levels of mizoribine to be increased to more than 3 μg/mL in most of the patients. Although SLEDAI, anti-ds-DNA antibody titer, CH-50, and serum albumin level did not significantly improve, urinary protein levels decreased, and it was possible to taper the dose of concomitant steroids. Using our definition of clinical response, 10 of the 17 patients were responders and 4 of them were nonresponders. The average peak serum mizoribine concentration of the responders was as high as 3.5 μg/mL. Elevation of serum liver enzymes was seen in 1 patient, and hyperuricemia occurred in 4 cases, but none of these adverse events were serious.

Conclusion

Intermittent administration of mizoribine can increase blood levels and may be effective for refractory lupus nephritis.

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Conflict of interest

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Authors and Affiliations

  1. Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan

    Eiko Nishi, Hiroe Ogawa, Hayato Nagasawa, Hirofumi Takei, Ayumi Okuyama, Tsuneo Kondo, Koji Nishimura, Ryota Sakai, Tatsuya Ito & Koichi Amano

  2. Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan

    Hideto Kameda, Takahiko Kurasawa, Yuichiro Shirai & Tsutomu Takeuchi

  3. Department of Internal Medicine, Saitama Yorii Hospital, 395 Yodo, Yorii, Ohsato County, Saitama, 369-1211, Japan

    Tatsuya Ito

Authors
  1. Eiko Nishi
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  2. Hideto Kameda
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  3. Hiroe Ogawa
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  4. Hayato Nagasawa
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  5. Hirofumi Takei
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  11. Ryota Sakai
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  12. Tatsuya Ito
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  13. Tsutomu Takeuchi
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  14. Koichi Amano
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Corresponding author

Correspondence to Koichi Amano.

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Nishi, E., Kameda, H., Ogawa, H. et al. Efficacy of weekly mizoribine pulse therapy in refractory lupus nephritis. Mod Rheumatol 23, 97–103 (2013). https://doi.org/10.1007/s10165-012-0645-6

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  • DOI: https://doi.org/10.1007/s10165-012-0645-6

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