• 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.