You Yijun, Zhou Zhuochao, Wang Fan, Li Jian, Liu Honglei, Cheng Xiaobing, Su Yutong, Chen Xiaowei, Zheng Hui, Sun Yue, Shi Hui, Hu Qiongyi, Xu Jing, Teng Jialin, Yang Chengde, Ye Junna
Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
JAMA Netw Open. 2024 Sep 3;7(9):e2432131. doi: 10.1001/jamanetworkopen.2024.32131.
Anti-double-stranded DNA (dsDNA) antibody has been reported to have a close relationship with systemic lupus erythematosus (SLE) flares and participates in the pathogenesis of lupus nephritis (LN) as well as causing damage to other organs. However, whether early use of mycophenolate mofetil (MMF) could prevent SLE flares is not clear.
To assess the efficacy and safety of MMF plus prednisone and hydroxychloroquine sulfate compared with prednisone and hydroxychloroquine sulfate alone in patients with SLE.
DESIGN, SETTING, AND PARTICIPANTS: This investigator-initiated, multicenter, observer-blinded randomized clinical trial enrolled 130 participants aged 18 to 65 years and was conducted in 3 hospitals across China. Treatment-naive patients with newly diagnosed SLE, a high titer of anti-dsDNA antibody, and no major organ involvement were included. The study was started September 1, 2018, and the follow-up was completed September 30, 2021. Data were analyzed from December 1, 2021, to March 31, 2022.
Patients were randomized 1:1 to receive oral prednisone (0.5 mg/kg/d) and hydroxychloroquine sulfate (5 mg/kg/d) (control group) or prednisone (0.5 mg/kg/d) and hydroxychloroquine sulfate (5 mg/kg/d) plus MMF (500 mg twice daily) (MMF group) for 96 weeks.
The primary outcome was the proportion of patients presenting with flares according to the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Flare Index. The secondary outcomes included the proportion with lupus low disease activity state at week 96, 36-Item Short Form Health Survey scores before and after treatment, proportion of adverse events (AEs), and changes in SLEDAI-2000 scores and prednisone doses.
Among 130 randomized patients (mean [SD] age, 34.5 [12.5] years; 112 [86.2%] women), 119 (91.5%) completed the follow-up. The risk of severe flare was significantly lower in the MMF group (7 of 65 [10.8%]) vs the control group (18 of 65 [27.7%]) (relative risk [RR], 0.39 [95% CI, 0.17-0.87]; P = .01). Additionally, 1 of 65 patients in the MMF group (1.5%) and 9 of 65 in the control group (13.8%) manifested LN (RR, 0.11 [95% CI, 0.01-0.85]; P = .008). Most common serious study drug-related AEs were infections (20 of 65 [30.8%] in the control group and 22 of 65 [33.8%] in the MMF group).
The findings of this randomized clinical trial suggest that MMF may reduce the rate of severe flare and lower the incidence of LN in patients with new-onset SLE and a high titer of anti-dsDNA antibody without major organ involvement.
Chinese Clinical Trial Registry: ChiCTR1800017540.
抗双链DNA（dsDNA）抗体与系统性红斑狼疮（SLE）发作密切相关，参与狼疮性肾炎（LN）的发病机制，并对其他器官造成损害。然而，早期使用霉酚酸酯（MMF）是否能预防SLE发作尚不清楚。
评估MMF联合泼尼松和硫酸羟氯喹与单独使用泼尼松和硫酸羟氯喹相比，对SLE患者的疗效和安全性。
设计、地点和参与者：这项由研究者发起的多中心、观察者盲法随机临床试验纳入了130名年龄在18至65岁之间的参与者，在中国的3家医院进行。纳入初治的新诊断SLE患者，其抗dsDNA抗体滴度高且无主要器官受累。研究于2018年9月1日开始，随访于2021年9月30日完成。数据于2021年12月1日至2022年3月31日进行分析。
患者按1:1随机分组，接受口服泼尼松（0.5mg/kg/d）和硫酸羟氯喹（5mg/kg/d）（对照组）或泼尼松（0.5mg/kg/d）、硫酸羟氯喹（5mg/kg/d）加MMF（500mg，每日两次）（MMF组），为期96周。
主要结局是根据狼疮性红斑全国评估-系统性红斑狼疮疾病活动指数（SELENA-SLEDAI）发作指数出现发作的患者比例。次要结局包括第96周时狼疮低疾病活动状态的比例、治疗前后的36项简明健康调查评分、不良事件（AE）比例以及SLEDAI-2000评分和泼尼松剂量的变化。
在130名随机分组的患者中（平均[标准差]年龄为34.5[12.5]岁；112名[86.2%]为女性），119名（91.5%）完成了随访。MMF组严重发作的风险（65例中的第7例[10.8%]）显著低于对照组（65例中的第18例[27.7%]）（相对风险[RR]，0.39[95%置信区间为0.17 - 0.87]；P = 0.01）。此外，MMF组65例患者中有1例（1.5%）出现LN，对照组65例中有9例（13.8%）出现LN（RR，0.11[95%置信区间为0.01 - 0.85]；P = 0.
