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. DESIGN: 24-week randomized, open-label, multicenter study. (ClinicalTrials.gov: NCT00876616). SETTING: 26 renal centers in China. PATIENTS: Adults (aged 18 to 65 years) with biopsy-proven LN. INTERVENTION: 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. MEASUREMENTS: 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]). LIMITATION: The study was limited to 24 weeks of follow-up. CONCLUSION:Multitarget therapy provides superior efficacy compared with intravenous cyclophosphamide as induction therapy for LN. PRIMARY FUNDING SOURCE: National Basic Research Program of China, National Key Technology R&D Program.
RCT Entities:
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. DESIGN: 24-week randomized, open-label, multicenter study. (ClinicalTrials.gov: NCT00876616). SETTING: 26 renal centers in China. PATIENTS: Adults (aged 18 to 65 years) with biopsy-proven LN. INTERVENTION: 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. MEASUREMENTS: 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]). LIMITATION: The study was limited to 24 weeks of follow-up. CONCLUSION: Multitarget therapy provides superior efficacy compared with intravenous cyclophosphamide as induction therapy for LN. PRIMARY FUNDING SOURCE: National Basic Research Program of China, National Key Technology R&D Program.