Vol.23 No.1

Original Article

Efficacy of weekly mizoribine pulse therapy in refractory lupus nephritis

Authors

Eiko Nishi1 , Hideto Kameda2 , Hiroe Ogawa1 , Hayato Nagasawa1 , Hirofumi Takei1 , Ayumi Okuyama1 , Takahiko Kurasawa2 , Tsuneo Kondo1 , Koji Nishimura1 , Yuichiro Shirai2 , Ryota Sakai1 , Tatsuya Ito1,3, Tsutomu Takeuchi2, Koichi Amano1

  • Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan
  • Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan
  • Department of Internal Medicine, Saitama Yorii Hospital, 395 Yodo, Yorii, Ohsato County, Saitama, 369-1211, Japan
Received:

2 December 2011

Accepted:

22 March 2012

Published online:

22 April 2012

Full Text

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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.

Key words

Lupus nephritis - Mizoribine