Zhihong Liu, MD; Haitao Zhang, MD; Zhangsuo Liu, MD; Changying Xing, PhD; Ping Fu, MD; Zhaohui Ni, MD; Jianghua Chen, MD; Hongli Lin, MD; Fuyou Liu, MD; Yongcheng He, MD; Yani He, MD; Lining Miao, MD; Nan Chen, MD; Ying Li, MD; Yong Gu, MD; Wei Shi, MD; Weixin Hu, MD; Zhengzhao Liu, MD; Hao Bao, MD; Caihong Zeng, PhD; Minlin Zhou, MD
Grant Support: By the National Basic Research Program of China (973 Program, No. 2012CB517600, No. 2012CB517606), National Key Technology R&D Program (2011BA I10B04, 2013BAI09B04).
Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1030.
Reproducible Research Statement:Study protocol: Available at www.annals.org. Statistical code: Available from Dr. Zhang at firstname.lastname@example.org. Data set: not available.
Requests for Single Reprints: Zhihong Liu, MD, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing 210016, China; e-mail, email@example.com.
Current Author Addresses: Drs. Zhihong Liu, Zhang, Hu, Zhengzhao Liu, Bao, Zeng, and Zhou: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, China, 210016.
Dr. Zhangsuo Liu: The First Affiliated Hospital, Zhengzhou University, No. 1 Jianshe Road, Zhengzhou, Henan, China, 450052.
Dr. Xing: The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, China, 210029.
Dr. Fu: West China Hospital, 37 Guoxue Xiang, Wuhou District, Chengdu, China, 610041.
Dr. Ni: Renji Hospital, Shanghai Jiaotong University School of Medicine, 160 Pujian Road, Shanghai, China, 200127.
Dr. Jianghua Chen: The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, China, 310003.
Dr. Lin: The First Affiliated Hospital of Dalian Medical University, NO 222, Zhongshan Road, Dalian, China, 116011.
Dr. Fuyou Liu: The Second Xiangya Hospital, Central South University, No. 139 Renmin Middle Road, Changsha, Hunan, China, 410011.
Dr. Yongcheng He: Shenzhen Second People's Hospital, 3002 West Sungang Road, Futian District, Shenzhen, China, 518035.
Dr. Yani He: Daping Hospital, Third Military Medical University, 10 Changjiangzhilu Daping, Yuzhong District, Chongqing, China, 400042.
Dr. Miao: The Second Hospital of Jilin University, Ziqiang Street 218, Changchun, China, 130041.
Dr. Nan Chen: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 RuiJin Er Lu, Shanghai, China, 200025.
Dr. Li: The Third Hospital of Hebei Medical University, 102 Youyi North Street, Shijiazhuang, Hebei Province, China, 050081.
Dr. Gu: Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040.
Dr. Shi: Guangdong General Hospital, Guangdong Academy of Medical Science, 106 Zhongshan Er Road, Guangzhou, China, 510080.
Author Contributions: Conception and design: Zhihong Liu, H. Zhang, Zhangsuo Liu. P. Fu.
Analysis and interpretation of the data: Zhihong Liu, H. Zhang, Zhangsuo Liu, P. Fu, Zhengzhao Liu, H. Bao, C. Zeng.
Drafting of the article: Zhihong Liu, H. Zhang, P. Fu, H. Bao, C. Zeng.
Critical revision of the article for important intellectual content: Zhihong Liu, H. Zhang, Zhangsuo Liu, P. Fu, Zhengzhao Liu, H. Bao, C. Zeng, M. Zhou.
Final approval of the article: Zhihong Liu, H. Zhang, Zhangsuo Liu, C. Xing, P. Fu, Z. Ni, J. Chen, H. Lin, F. Liu, Yani He, L. Miao, N. Chen, Y. Gu, W. Shi, W. Hu, H. Bao, C. Zeng, M. Zhou.
Provision of study materials or patients: Zhihong Liu, H. Zhang, C. Xing, P. Fu, Z. Ni, J. Chen, H. Lin, F. Liu, Yongcheng He, Yani He, L. Miao, N. Chen, Y. Li, Y. Gu, W. Shi, W. Hu, Zhengzhao Liu, C. Zeng.
Statistical expertise: P. Fu, M. Zhou.
Obtaining of funding: Zhihong Liu, H. Zhang, P. Fu.
Administrative, technical, or logistic support: Zhihong Liu, H. Zhang, Zhengzhao Liu.
Collection and assembly of data: Zhihong Liu, H. Zhang, Zhangsuo Liu, C. Xing, P. Fu, J. Chen, H. Lin, F. Liu, Yongcheng He, N. Chen, W. Hu, Zhengzhao Liu, C. Zeng.
Treatment of lupus nephritis (LN) remains challenging.
To assess the efficacy and safety of a multitarget therapy consisting of tacrolimus, mycophenolate mofetil, and steroid compared with intravenous cyclophosphamide and steroid as induction therapy for LN.
24-week randomized, open-label, multicenter study. (ClinicalTrials.gov: NCT00876616)
26 renal centers in China.
Adults (aged 18 to 65 years) with biopsy-proven LN.
Tacrolimus, 4 mg/d, and mycophenolate mofetil, 1.0 g/d, versus intravenous cyclophosphamide with a starting dose of 0.75 (adjusted to 0.5 to 1.0) g/m2 of body surface area every 4 weeks for 6 months. Both groups received 3 days of pulse methylprednisolone followed by a tapering course of oral prednisone therapy.
The primary end point was complete remission at 24 weeks. Secondary end points included overall response (complete and partial remission), time to overall response, and adverse events.
After 24 weeks of therapy, more patients in the multitarget group (45.9%) than in the intravenous cyclophosphamide group (25.6%) showed complete remission (difference, 20.3 percentage points [95% CI, 10.0 to 30.6 percentage points]; P < 0.001). The overall response incidence was higher in the multitarget group than in the intravenous cyclophosphamide group (83.5% vs. 63.0%; difference, 20.4 percentage points [CI, 10.3 to 30.6 percentage points]; P < 0.001), and the median time to overall response was shorter in the multitarget group (difference, −4.1 weeks [CI, −7.9 to −2.1 weeks]). Incidence of adverse events did not differ between the multitarget and intravenous cyclophosphamide groups (50.3% [91 of 181] vs. 52.5% [95 of 181]).
The study was limited to 24 weeks of follow-up.
Multitarget therapy provides superior efficacy compared with intravenous cyclophosphamide as induction therapy for LN.
National Basic Research Program of China, National Key Technology R&D Program.
Liu Z, Zhang H, Liu Z, Xing C, Fu P, Ni Z, et al. Multitarget Therapy for Induction Treatment of Lupus Nephritis: A Randomized Trial. Ann Intern Med. ;162:18–26. doi: 10.7326/M14-1030
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Published: Ann Intern Med. 2015;162(1):18-26.
Autoimmune Kidney Disease, Lupus Erythematosus, Nephrology, Rheumatology.
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