A randomized open-label comparative study of conventional therapy versus mizoribine onlay therapy in patients with steroid-resistant nephrotic syndrome (postmarketing survey).
BACKGROUND
A previous double-blind 24-week clinical trial of mizoribine (MZ) vs placebo in steroid-resistant primary nephrotic syndrome (SRPNS) showed that MZ was more effective than placebo in reducing the rate of deterioration of renal function. The present study was conducted to evaluate the efficacy and safety of MZ in patients with SRPNS after 2 years' treatment.


METHODS
A multicenter randomized open-label controlled trial in patients with SRPNS was conducted as a 2-year prospective postmarketing study.


RESULTS
There was a significant imbalance in the baseline serum albumin level (s-Alb) between the conventional therapy (CT) and MZ onlay therapy groups. Early dropouts were more frequent in the subset of patients in the CT group having a baseline s-Alb < or =3 g/dl. Therefore, the primary analysis (urinary protein level (UP)-improving effect) was performed using a mixed-effects model, with stratification according to the baseline s-Alb value. The analysis revealed that, in the subset of 34 patients with membranous nephropathy (MN) within the stratum of patients with baseline s-Alb < or =3 g/dl (n = 52), the rate of change (slope of change in the UP level/month), in terms of the log (UP+0.2), was -0.0577 in those allocated to the MZ group and -0.0227 in those allocated to the CT group (P = 0.058). In the stratum of patients with a baseline s-Alb >3 g/dl (n = 97), there were no significant differences in the UP between the two treatment groups. Hence, MZ onlay therapy was not considered to be efficacious in this group of patients. No serious adverse reactions to the drug were observed.


CONCLUSIONS
The present study yielded significant results, in that it suggested the possibility that long-term MZ therapy may afford further reduction of the UP, in addition to that obtained following CT, in particular, in MN patients in a severe nephrotic state.
Shibasaki
Toshiaki
T
Department of Pharmacotherapeutics, Kyoritsu College of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan. shibasaki-ts@kyoritsu.ph.ac.jp
Koyama
Akio
A
Hishida
Akira
A
Muso
Eri
E
Osawa
Gengo
G
Yamabe
Hideaki
H
Shiiki
Hideo
H
Makino
Hirofumi
H
Sato
Hiroshi
H
Ishikawa
Isao
I
Maeda
Kenji
K
Tomita
Kimio
K
Arakawa
Masaaki
M
Ishida
Masashi
M
Sato
Masashi
M
Nagase
Mitsumasa
M
Kashihara
Naoki
N
Yorioka
Noriaki
N
Koike
Takao
T
Saito
Takao
T
Harada
Takashi
T
Mitarai
Tetsuya
T
Sugisaki
Tetsuzo
T
Nagasawa
Toshihiko
T
Tomino
Yasuhiko
Y
Nojima
Yoshihisa
Y
Kobayashi
Yutaka
Y
Sakai
Osamu
O
D000328:Adult; D004351:Drug Resistance; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000188:drug therapy*; D010352:Patient Dropouts; D011358:Product Surveillance, Postmarketing; D011507:Proteinuria / Q000188:drug therapy; D012074:Remission Induction; D012263:Ribonucleosides / Q000008:administration & dosage* / Q000009:adverse effects; D013256:Steroids / Q000008:administration & dosage
D007166:Immunosuppressive Agents; D012263:Ribonucleosides; D013256:Steroids; C010052:mizoribine