霉酚酸酯与硫唑嘌呤作为狼疮性肾炎维持治疗的比较。

Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis.

机构信息

Department of Medicine, University of North Carolina, Chapel Hill, USA.

出版信息

N Engl J Med. 2011 Nov 17;365(20):1886-95. doi: 10.1056/NEJMoa1014460.

DOI:10.1056/NEJMoa1014460

PMID:22087680

Abstract

BACKGROUND

Maintenance therapy, often with azathioprine or mycophenolate mofetil, is required to consolidate remission and prevent relapse after the initial control of lupus nephritis.

METHODS

We carried out a 36-month, randomized, double-blind, double-dummy, phase 3 study comparing oral mycophenolate mofetil (2 g per day) and oral azathioprine (2 mg per kilogram of body weight per day), plus placebo in each group, in patients who met response criteria during a 6-month induction trial. The study group underwent repeat randomization in a 1:1 ratio. Up to 10 mg of prednisone per day or its equivalent was permitted. The primary efficacy end point was the time to treatment failure, which was defined as death, end-stage renal disease, doubling of the serum creatinine level, renal flare, or rescue therapy for lupus nephritis. Secondary assessments included the time to the individual components of treatment failure and adverse events.

RESULTS

A total of 227 patients were randomly assigned to maintenance treatment (116 to mycophenolate mofetil and 111 to azathioprine). Mycophenolate mofetil was superior to azathioprine with respect to the primary end point, time to treatment failure (hazard ratio, 0.44; 95% confidence interval, 0.25 to 0.77; P = 0.003), and with respect to time to renal flare and time to rescue therapy (hazard ratio, <1.00; P < 0.05). Observed rates of treatment failure were 16.4% (19 of 116 patients) in the mycophenolate mofetil group and 32.4% (36 of 111) in the azathioprine group. Adverse events, most commonly minor infections and gastrointestinal disorders, occurred in more than 95% of the patients in both groups (P = 0.68). Serious adverse events occurred in 33.3% of patients in the azathioprine group and in 23.5% of those in the mycophenolate mofetil group (P = 0.11), and the rate of withdrawal due to adverse events was higher with azathioprine than with mycophenolate mofetil (39.6% vs. 25.2%, P = 0.02).

CONCLUSIONS

Mycophenolate mofetil was superior to azathioprine in maintaining a renal response to treatment and in preventing relapse in patients with lupus nephritis who had a response to induction therapy. (Funded by Vifor Pharma [formerly Aspreva]; ALMS ClinicalTrials.gov number, NCT00377637.).

摘要

背景

在狼疮肾炎初始控制后，需要维持治疗（通常使用硫唑嘌呤或霉酚酸酯）以巩固缓解并预防复发。

方法

我们进行了一项为期 36 个月、随机、双盲、双模拟、3 期研究，比较了在 6 个月诱导试验中符合缓解标准的患者中，口服霉酚酸酯（每天 2 克）和口服硫唑嘌呤（每天每公斤体重 2 毫克），每组加安慰剂。研究组以 1:1 的比例进行重复随机分组。每天最多允许使用 10 毫克泼尼松或其等效药物。主要疗效终点是治疗失败时间，定义为死亡、终末期肾病、血清肌酐水平翻倍、肾脏复发或狼疮肾炎的抢救治疗。次要评估包括治疗失败和不良事件的各个组成部分的时间。

结果

共有 227 名患者被随机分配至维持治疗（116 名接受霉酚酸酯治疗，111 名接受硫唑嘌呤治疗）。与硫唑嘌呤相比，霉酚酸酯在主要终点、治疗失败时间（风险比，0.44；95%置信区间，0.25 至 0.77；P = 0.003）和肾脏复发时间以及抢救治疗时间（风险比，<1.00；P < 0.05）方面均有优势。霉酚酸酯组治疗失败的发生率为 16.4%（19/116 例），硫唑嘌呤组为 32.4%（36/111 例）。两组均有超过 95%的患者出现治疗相关不良事件，最常见的是轻微感染和胃肠道疾病（P = 0.68）。硫唑嘌呤组 33.3%的患者发生严重不良事件，霉酚酸酯组为 23.5%（P = 0.11），硫唑嘌呤组因不良事件退出治疗的比例高于霉酚酸酯组（39.6%比 25.2%，P = 0.02）。