Yoshidome Kouichi, Takei Syuji, Imanaka Hiroyuki, Maeno Nobuaki, Ohkawa Toshiya, Kawano Yoshifumi
Department of Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Pediatr Int. 2004 Aug;46(4):444-9. doi: 10.1111/j.1442-200x.2004.01923.x.
Mizoribine (MZR) is a novel immunosuppressant developed in Japan. As MZR is reported to be less toxic than other cytotoxic drugs, it is frequently used in Japan in the treatment of adult patients with rheumatoid arthritis or lupus nephritis. The objective of this study was to evaluate the efficacy of MZR in children with SLE. Nine female children with lupus nephritis who had undergone renal biopsy before starting MZR, were involved in this study. Their mean disease duration was 4.8 years at the time MZR treatment was initiated. Patients who had received intensive medications, such as methyl-prednisolone pulse therapy, intravenous cyclophosphamide pulse therapy, and/or other immunosuppressants, within the 4 months prior to the start of the study, were excluded.
Patients treated with 3 mg/kg per day of MZR were monitored every month for up to 1 year. The efficacy of MZR was evaluated by the changes from baseline values of serum C3, serum C4, anti-dsDNA antibody titer, erythrocyte sedimentation rate (ESR), urinary protein, dosage of prednisolone (PSL), and the sum of the scores defined by these parameters.
Favorable changes were observed in C3 and ESR after 2 months and 3 months of MZR therapy, respectively. At 3 months of MZR therapy, the sum of scores defined by the parameters for disease activity indicated that MZR was more effective in non-class IV nephritis patients (n = 5) than in class IV nephritis patients (n = 4) (P = 0.0197). All nine children involved in the study tolerated the MZR therapy well during the study.
MZR was safe in lupus children, but its efficacy was limited in patients with non-class IV nephritis. Further study is necessary, in which higher dosages and/or earlier use of MZR is provided to a larger number of children.
咪唑立宾（MZR）是一种在日本研发的新型免疫抑制剂。据报道，MZR的毒性低于其他细胞毒性药物，在日本常用于治疗成年类风湿关节炎或狼疮性肾炎患者。本研究的目的是评估MZR对儿童系统性红斑狼疮（SLE）的疗效。9名患有狼疮性肾炎的女童在开始使用MZR前接受了肾活检，并参与了本研究。在开始MZR治疗时，她们的平均病程为4.8年。在研究开始前4个月内接受过强化药物治疗（如甲泼尼龙冲击疗法、静脉注射环磷酰胺冲击疗法和/或其他免疫抑制剂）的患者被排除。
对每天接受3mg/kg MZR治疗的患者进行长达1年的每月监测。通过血清C3、血清C4、抗双链DNA抗体滴度、红细胞沉降率（ESR）、尿蛋白、泼尼松龙（PSL）剂量以及由这些参数定义的分数总和相对于基线值的变化来评估MZR的疗效。
分别在MZR治疗2个月和3个月后观察到C3和ESR出现有利变化。在MZR治疗3个月时，由疾病活动参数定义的分数总和表明，MZR对非IV级肾炎患者（n = 5）比对IV级肾炎患者（n = 4）更有效（P = 0.0197）。参与研究的所有9名儿童在研究期间对MZR治疗耐受性良好。
MZR对狼疮患儿是安全的，但其疗效在非IV级肾炎患者中有限。有必要进行进一步研究，为更多儿童提供更高剂量和/或更早使用MZR的治疗方案。
