A multicenter trial of mizoribine compared with placebo in children with frequently relapsing nephrotic syndrome.
BACKGROUND
The use of corticosteroids or cytotoxic/immunosuppressive agents such as cyclophosphamide, chlorambucil, and cyclosporine for the treatment of frequently relapsing nephrotic syndrome (FRNS) is limited because of their adverse effects. This study was conducted to evaluate the efficacy and safety of mizoribine, a relatively new immunosuppressive drug developed in Japan, in children with FRNS.


METHODS
A double-blind, placebo-controlled, multicenter trial was carried out in children, from 2 to 19 years old, with FRNS. At relapse, patients were treated with prednisolone. According to a dynamic allocation, mizoribine or a placebo was concurrently administered to each patient. Prednisolone was gradually tapered and discontinued within 12 weeks. The test drug was maintained for 48 weeks. The primary end point was the relapse rate (the total number of relapses/the total treatment days for all patients). Analyses were performed according to the intention-to-treat principle.


RESULTS
The primary analysis was conducted on 99 mizoribine- and 98 placebo-treated patients. The relapse rate was lower in the mizoribine group than in the placebo group (0.0055 vs. 0.0067; ratio 0.81, 95% CI, 0.61 to 1.05, P = 0.12). The hazard ratio of the cumulative remission rate between the two groups was 0.79 (95% CI, 0. 57 to 1.08). In the subgroups consisting of patients 10 years old or younger, the relapse rate ratio between the mizoribine subgroup (54 patients) and the placebo subgroup (57 patients) was 0.66 (95% CI, 0. 44 to 0.94, P = 0.017). The hazard ratio of the cumulative remission rate between the two subgroups was 0.56 (95% CI, 0.37 to 0.85, P = 0. 007). Hyperuricemia was the most common adverse event with mizoribine (16%), but was transient.


CONCLUSIONS
Compared with the placebo, mizoribine significantly decreased the relapse rate and prolonged the remission period in the subgroup consisting of patients 10 years old or younger. This drug may be useful in young children with FRNS who generally relapse more frequently than older children.
Yoshioka
K
K
Department of Pediatrics, Kinki University School of Medicine, Osaka-sayama, Japan. kzyoshio@med.kindai.ac.jp
Ohashi
Y
Y
Sakai
T
T
Ito
H
H
Yoshikawa
N
N
Nakamura
H
H
Tanizawa
T
T
Wada
H
H
Maki
S
S
D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy*; D010919:Placebos; D011239:Prednisolone / Q000008:administration & dosage; D012263:Ribonucleosides / Q000008:administration & dosage* / Q000009:adverse effects; D055502:Secondary Prevention
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D010919:Placebos; D012263:Ribonucleosides; C010052:mizoribine; D011239:Prednisolone