Zhang Haitao, Liu Zhengzhao, Zhou Minlin, Liu Zhangsuo, Chen Jianghua, Xing Changying, Lin Hongli, Ni Zhaohui, Fu Ping, Liu Fuyou, Chen Nan, He Yongcheng, Liu Jianshe, Zeng Caihong, Liu Zhihong
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Department of Nephrology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
J Am Soc Nephrol. 2017 Dec;28(12):3671-3678. doi: 10.1681/ASN.2017030263. Epub 2017 Jul 31.
Our previous studies showed that multitarget therapy is superior in efficacy to intravenous cyclophosphamide as an induction treatment for lupus nephritis in Asian populations. We conducted an open label, multicenter study for 18 months as an extension of the prior induction therapy trial in 19 renal centers in China to assess the efficacy and safety of multitarget maintenance therapy in patients who had responded at 24 weeks during the induction phase. Patients who had undergone multitarget induction therapy continued to receive multitarget therapy (tacrolimus, 2-3 mg/d; mycophenolate mofetil, 0.50-0.75 g/d; prednisone, 10 mg/d), and patients who had received intravenous cyclophosphamide induction treatment received azathioprine (2 mg/kg per day) plus prednisone (10 mg/d). We assessed the renal relapse rate during maintenance therapy as the primary outcome. We recruited 116 patients in the multitarget group and 90 patients in the azathioprine group. The multitarget and azathioprine groups had similar cumulative renal relapse rates (5.47% versus 7.62%, respectively; adjusted hazard ratio, 0.82; 95% confidence interval, 0.25 to 2.67; 0.74), and serum creatinine levels and eGFR remained stable in both groups. The azathioprine group had more adverse events (44.4% versus 16.4% for multitarget therapy; <0.01), and the multitarget group had a lower withdrawal rate due to adverse events (1.7% versus 8.9% for azathioprine; =0.02). In conclusion, multitarget therapy as a maintenance treatment for lupus nephritis resulted in a low renal relapse rate and fewer adverse events, suggesting that multitarget therapy is an effective and safe maintenance treatment for patients with lupus nephritis.
我们之前的研究表明,在亚洲人群中,多靶点治疗作为狼疮性肾炎的诱导治疗,其疗效优于静脉注射环磷酰胺。我们进行了一项为期18个月的开放标签、多中心研究,作为之前在中国19个肾脏中心进行的诱导治疗试验的扩展,以评估多靶点维持治疗对在诱导期24周时有反应的患者的疗效和安全性。接受多靶点诱导治疗的患者继续接受多靶点治疗(他克莫司,2 - 3毫克/天;霉酚酸酯,0.50 - 0.75克/天;泼尼松,10毫克/天),而接受静脉注射环磷酰胺诱导治疗的患者接受硫唑嘌呤(2毫克/千克/天)加泼尼松(10毫克/天)。我们将维持治疗期间的肾脏复发率作为主要结局进行评估。我们在多靶点组招募了116名患者,在硫唑嘌呤组招募了90名患者。多靶点组和硫唑嘌呤组的累积肾脏复发率相似(分别为5.47%和7.62%;调整后的风险比,0.82;95%置信区间,0.25至2.67;P = 0.74),两组的血清肌酐水平和估算肾小球滤过率均保持稳定。硫唑嘌呤组的不良事件更多(多靶点治疗组为16.4%,硫唑嘌呤组为44.4%;P<0.01),多靶点组因不良事件导致的停药率更低(硫唑嘌呤组为8.9%,多靶点组为1.7%;P = 0.02)。总之,多靶点治疗作为狼疮性肾炎的维持治疗,肾脏复发率低且不良事件少,表明多靶点治疗是狼疮性肾炎患者有效且安全的维持治疗方法。