他克莫司与霉酚酸酯治疗狼疮性肾炎诱导缓解的随机对照试验及长期随访
Tacrolimus versus mycophenolate mofetil for induction therapy of lupus nephritis: a randomised controlled trial and long-term follow-up.
机构信息
Department of Medicine, Tuen Mun Hospital, Hong Kong.
Department of Medicine, Princess Margaret Hospital, Hong Kong.
出版信息
Ann Rheum Dis. 2016 Jan;75(1):30-6. doi: 10.1136/annrheumdis-2014-206456. Epub 2014 Dec 30.
OBJECTIVE
To compare the efficacy of tacrolimus (TAC) and mycophenolate mofetil (MMF) for the initial therapy of lupus nephritis (LN).
STUDY DESIGN
This is an open randomised controlled parallel group study.
METHODS
Adult patients with biopsy-confirmed active LN (class III/IV/V) were randomised to receive prednisolone (0.6 mg/kg/day for 6 weeks and tapered) in combination with either TAC (0.06-0.1 mg/kg/day) or MMF (2-3 g/day) for 6 months. Good responders were shifted to azathioprine for maintenance. The primary outcome was the rate of complete renal response (CR) at 6 months and the secondary outcomes included partial renal response, renal flares and decline of renal function over time.
RESULTS
150 patients (92% women; aged 35.5±12.8 years; 81% class III/IV) were randomised (76 MMF, 74 TAC). At month 6, the rate of CR was 59% in the MMF and 62% in the TAC group (treatment difference: 3.0% (-12%, 18%); p=0.71). Major infective episodes occurred in 9.2% patients treated with MMF and in 5.4% patients treated with TAC (p=0.53). Maintenance therapy with azathioprine was given to 79% patients. After 60.8±26 months, proteinuric and nephritic renal flares developed in 24% and 18% of patients in the MMF group and 35% (p=0.12) and 27% (p=0.21) in the TAC group, respectively. The cumulative incidence of a composite outcome of decline of creatinine clearance by ≥30%, development of chronic kidney disease stage 4/5 or death was 21% in the MMF and 22% in the TAC group of patients (p=0.35).
CONCLUSIONS
TAC is non-inferior to MMF, when combined with prednisolone, for induction therapy of active LN. With azathioprine maintenance for 5 years, a non-significant trend of higher incidence of renal flares and renal function decline is observed with the TAC regimen.
TRIAL REGISTRATION NUMBER
Hospital Authority Research Ethics Committee Clinical Trial Registry (HARECCTR0500018; Hong Kong) and US ClinicalTrials.gov (NCT00371319).
目的
比较他克莫司（TAC）和霉酚酸酯（MMF）在狼疮肾炎（LN）初始治疗中的疗效。
研究设计
这是一项开放的随机对照平行组研究。
方法
成人活检证实的活动性 LN（III/IV/V 级）患者被随机分为泼尼松龙（6 周内 0.6mg/kg/天，然后逐渐减量）联合他克莫司（0.06-0.1mg/kg/天）或霉酚酸酯（2-3g/天）治疗 6 个月。完全缓解（CR）的患者转为硫唑嘌呤维持治疗。主要终点是 6 个月时的完全缓解率，次要终点包括部分缓解、肾复发和肾功能随时间下降。
结果
150 例患者（92%为女性；年龄 35.5±12.8 岁；81%为 III/IV 级）被随机分组（MMF 组 76 例，TAC 组 74 例）。6 个月时，MMF 组 CR 率为 59%，TAC 组为 62%（治疗差异：3.0%（-12%，18%）；p=0.71）。MMF 组 9.2%的患者和 TAC 组 5.4%的患者发生严重感染事件（p=0.53）。79%的患者接受硫唑嘌呤维持治疗。60.8±26 个月后，MMF 组 24%和 18%的患者出现蛋白尿和肾炎肾复发，TAC 组分别为 35%（p=0.12）和 27%（p=0.21）。MMF 组和 TAC 组患者发生肌酐清除率下降≥30%、慢性肾脏病 4/5 期或死亡的复合终点发生率分别为 21%和 22%（p=0.35）。
结论
在泼尼松龙联合治疗中，他克莫司与霉酚酸酯诱导治疗活动性 LN 时非劣效。5 年硫唑嘌呤维持治疗后，TAC 方案观察到肾复发和肾功能下降的发生率呈非显著性升高趋势。
试验注册
香港医管局研究伦理委员会临床试验注册处（HARECCTR0500018）和美国临床试验注册网站（NCT00371319）。
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