Multitarget therapy for induction treatment of lupus nephritis: a randomized trial.
BACKGROUND
Treatment of lupus nephritis (LN) remains challenging.


OBJECTIVE
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.


METHODS
24-week randomized, open-label, multicenter study. (ClinicalTrials.gov: NCT00876616).


METHODS
26 renal centers in China.


METHODS
Adults (aged 18 to 65 years) with biopsy-proven LN.


METHODS
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.


METHODS
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.


RESULTS
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]).


CONCLUSIONS
The study was limited to 24 weeks of follow-up.


CONCLUSIONS
Multitarget therapy provides superior efficacy compared with intravenous cyclophosphamide as induction therapy for LN.


BACKGROUND
National Basic Research Program of China, National Key Technology R&D Program.
Zhihong
Z
Liu
Haitao
H
Zhang
Zhangsuo
Z
Liu
Changying
C
Xing
Ping
P
Fu
Zhaohui
Z
Ni
Jianghua
J
Chen
Hongli
H
Lin
Fuyou
F
Liu
Yongcheng
Y
He
Yani
Y
He
Lining
L
Miao
Nan
N
Chen
Ying
Y
Li
Yong
Y
Gu
Wei
W
Shi
Weixin
W
Hu
Zhengzhao
Z
Liu
Hao
H
Bao
Caihong
C
Zeng
Minlin
M
Zhou
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010865:Pilot Projects; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D012074:Remission Induction; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus; D008775:Methylprednisolone