Wang Jingjing, Liu Fei, Yan Weili, Zhou Jianhua, Zhang Yu, Rong Liping, Jiang Xiaoyun, Zhao Fei, Zhu Chunhua, Wu Xiaochuan, Li Xiaoyan, Sun Shuzhen, Wang Jing, Wang Mo, Yang Qin, Xu Hong, Chen Jing, Liu Cuihua, Tian Ming, Feng Shipin, Duan Qinwei, Zhong Xuhui, Zhu Yun, Li Xiaozhong, Fu Haidong, Huang Lingfei, Ma Daqing, Ding Jie, Ye Qing, Mao Jianhua
Department of Nephrology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
Department of Clinical Epidemiology and Clinical Trial Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
JAMA Pediatr. 2025 May 12. doi: 10.1001/jamapediatrics.2025.0765.
Both tacrolimus (TAC) and mycophenolate mofetil (MMF) are recommended for children with frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). However, their comparative effectiveness and safety have not been evaluated through randomized clinical trials.
To compare the effectiveness and safety of TAC and MMF in children with FRNS or SDNS.
DESIGN, SETTING, AND PARTICIPANTS: In this multicenter, open-label randomized clinical trial conducted at 12 pediatric nephrology centers across China, 270 children aged 2 to 18 years with FRNS or SDNS were allocated at a 1:1 ratio to treatment with either TAC or MMF. The study was conducted from November 2019 to July 2023, and data analysis was completed from July 2023 to March 2024.
Patients received either TAC (0.025-0.050 mg/kg, orally twice daily) or MMF (10-15 mg/kg, orally twice daily) for 1 year, along with a tapering regimen of steroids.
The primary end point was 1-year relapse-free survival. Relapse frequency, cumulative steroid dosage, and safety profiles were also evaluated.
A total of 292 patients from 12 care centers were assessed for eligibility, and 270 patients were randomized to receive either TAC (n = 135) or MMF (n = 135). Among 270 patients, median (IQR) age was 6.91 (4.25-9.96) years, and 70 patients (25.9%) were female. Compared with MMF, the 1-year relapse-free survival rate in the TAC group was 1.86-fold higher (hazard ratio [HR], 2.86; 95% CI, 1.79-4.76; P < .001) in the intention-to-treat analysis. This difference was also significant after adjusting for the per-protocol analysis (HR, 2.78; 95% CI, 1.72-4.55; P < .001). The mean (SD) time to first relapse was significantly longer in the TAC group (323.99 [98.33] days) compared to the MMF group (263.21 [132.84] days). Furthermore, the TAC group showed a lower annual relapse rate than the MMF group (17.78% vs 41.48%) and required a significantly lower mean (SD) cumulative steroid dose (0.22 [0.10] mg/kg/day vs 0.34 [0.22] mg/kg/day). The safety profile was similar in both groups.
In this randomized clinical trial, compared with MMF, a 1-year course of TAC therapy significantly extended the period of relapse-free survival in children with FRNS or SDNS.
ClinicalTrials.gov Identifier: NCT04048161.
他克莫司（TAC）和霉酚酸酯（MMF）均被推荐用于频繁复发的肾病综合征（FRNS）或激素依赖型肾病综合征（SDNS）患儿。然而，它们的相对有效性和安全性尚未通过随机临床试验进行评估。
比较TAC和MMF在FRNS或SDNS患儿中的有效性和安全性。
设计、地点和参与者：在这项在中国12个儿科肾脏病中心进行的多中心、开放标签随机临床试验中，270名2至18岁的FRNS或SDNS患儿按1:1的比例分配接受TAC或MMF治疗。该研究于2019年11月至2023年7月进行，数据分析于2023年7月至2024年3月完成。
患者接受TAC（0.025 - 0.050 mg/kg，口服，每日两次）或MMF（10 - 15 mg/kg，口服，每日两次）治疗1年，并配合激素减量方案。
主要终点是1年无复发生存率。还评估了复发频率、累积激素剂量和安全性。
来自12个护理中心的292名患者接受了资格评估，270名患者被随机分配接受TAC（n = 135）或MMF（n = 135）治疗。在270名患者中，中位（IQR）年龄为6.91（4.25 - 9.96）岁，70名患者（25.9%）为女性。在意向性分析中，与MMF相比，TAC组的1年无复发生存率高1.86倍（风险比[HR]，2.86；95%置信区间，1.79 - 4.76；P <.001）。在按方案分析调整后，这种差异也很显著（HR，2.78；95%置信区间，1.72 - 4.55；P <.001）。与MMF组（263.21 [132.84]天）相比，TAC组首次复发的平均（SD）时间显著更长（323.99 [98.33]天）。此外，TAC组的年复发率低于MMF组（17.78%对41.48%），并且所需的平均（SD）累积激素剂量显著更低（0.22 [0.10] mg/kg/天对0.34 [0.22] mg/kg/天）。两组的安全性相似。
在这项随机临床试验中，与MMF相比，1年疗程的TAC治疗显著延长了FRNS或SDNS患儿的无复发生存时间。
ClinicalTrials.gov标识符：NCT04048161。
