Mizoribine oral pulse therapy for patients with disease flare of lupus nephritis.
OBJECTIVE
Mizoribine (MZR) is a newly developed immunosuppressive agent in Japan. To relieve disease flare of lupus nephritis, a prospective pilot study of oral MZR pulse therapy (a phase II trial) is conducted as an alternative therapy to dose up of corticosteroids.


METHODS
Six Japanese patients with biopsy-proven lupus nephritis who experienced disease flare were prospectively evaluated. MZR at a dose of 5 - 10 mg/kg per day (up to 500 mg) in 1 or 2 divided daily doses was orally administered twice a week for 3 months. At the time of disease flare, 4 patients had refused to take dose up of corticosteroids, and the other 2 had complained of opportunistic infection.


RESULTS
At presentation, urine protein excretion, serum hemolytic complement activity (CH50) and serum anti-dsDNA antibody were 1.9 +/- 0.6 g/day, 15.7 +/- 5.8 U/ml (normal 23 - 46 U/ml) and 164.8 +/- 184.0 IU/ml (normal < 12.0 IU/ml), respectively. Urine protein excretion and serum anti-dsDNA antibody decreased significantly following MZR oral pulse therapy (0.2 +/- 0.1 g/day and 29.7 +/- 23.4 IU/ml (p < 0.05), respectively), and serum CH50 recovered to normal (35.1 +/- 10.4 U/ml, p < 0.05). Moreover, a significant histologic improvement was observed in a patient who received repeat renal biopsies at pre- and post-treatment. Reported peak serum MZR levels enough to inhibit human mixed-lymphocyte reaction (3.0 - 6.0 microg/ml) were achieved in all patients. No serious adverse effects were observed.


CONCLUSIONS
Although we had no control subjects in this series, MZR oral pulse therapy may be of benefit to a proportion of patients with disease flare of lupus nephritis as an alternative therapy to dose up of corticosteroids.
Tanaka
H
H
Department of Pediatrics, Hirosaki University School of Medicine, Hirosaki, Japan. hirotana@cc.hirosaki-u.ac.jp
Suzuki
K
K
Nakahata
T
T
Tsugawa
K
K
Ito
E
E
Waga
S
S
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002648:Child; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000188:drug therapy*; D008297:Male; D010865:Pilot Projects; D011446:Prospective Studies; D012263:Ribonucleosides / Q000008:administration & dosage / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D012263:Ribonucleosides; C010052:mizoribine