Rheumatology Department, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Saint-Luc University Hospital, Brussels 1200, Belgium.
Ann Rheum Dis. 2010 Dec;69(12):2083-9. doi: 10.1136/ard.2010.131995. Epub 2010 Sep 10.
Long-term immunosuppressive treatment does not efficiently prevent relapses of lupus nephritis (LN). This investigator-initiated randomised trial tested whether mycophenolate mofetil (MMF) was superior to azathioprine (AZA) as maintenance treatment.
A total of 105 patients with lupus with proliferative LN were included. All received three daily intravenous pulses of 750 mg methylprednisolone, followed by oral glucocorticoids and six fortnightly cyclophosphamide intravenous pulses of 500 mg. Based on randomisation performed at baseline, AZA (target dose: 2 mg/kg/day) or MMF (target dose: 2 g/day) was given at week 12. Analyses were by intent to treat. Time to renal flare was the primary end point. Mean (SD) follow-up of the intent-to-treat population was 48 (14) months.
The baseline clinical, biological and pathological characteristics of patients allocated to AZA or MMF did not differ. Renal flares were observed in 13 (25%) AZA-treated and 10 (19%) MMF-treated patients. Time to renal flare, to severe systemic flare, to benign flare and to renal remission did not statistically differ. Over a 3-year period, 24 h proteinuria, serum creatinine, serum albumin, serum C3, haemoglobin and global disease activity scores improved similarly in both groups. Doubling of serum creatinine occurred in four AZA-treated and three MMF-treated patients. Adverse events did not differ between the groups except for haematological cytopenias, which were statistically more frequent in the AZA group (p=0.03) but led only one patient to drop out.
Fewer renal flares were observed in patients receiving MMF but the difference did not reach statistical significance.
长期的免疫抑制治疗并不能有效地预防狼疮肾炎（LN）的复发。本项由研究者发起的随机试验旨在检验霉酚酸酯（MMF）是否优于硫唑嘌呤（AZA）作为维持治疗。
共纳入 105 例狼疮伴增生性 LN 患者。所有患者均接受了三个疗程的 750mg 甲基强的松龙静脉冲击治疗，随后给予口服糖皮质激素和六个疗程的每两周一次的 500mg 环磷酰胺静脉冲击治疗。根据基线时的随机分组，在第 12 周给予 AZA（目标剂量：2mg/kg/天）或 MMF（目标剂量：2g/天）。分析采用意向治疗。主要终点为肾脏复发时间。意向治疗人群的平均（SD）随访时间为 48（14）个月。
接受 AZA 或 MMF 治疗的患者的基线临床、生物学和病理学特征无差异。AZA 治疗组有 13 例（25%）和 MMF 治疗组有 10 例（19%）发生了肾脏复发。肾脏复发时间、严重全身复发时间、良性复发时间和肾脏缓解时间无统计学差异。在 3 年期间，两组患者的 24 小时蛋白尿、血清肌酐、血清白蛋白、血清 C3、血红蛋白和全球疾病活动评分均相似地改善。AZA 治疗组有 4 例和 MMF 治疗组有 3 例患者的血清肌酐加倍。两组之间的不良事件无差异，但 AZA 组的血液学细胞减少症更为频繁（p=0.03），但仅导致 1 例患者退出。
接受 MMF 治疗的患者肾脏复发较少，但差异无统计学意义。
