Multitarget Therapy for Induction Treatment of Lupus Nephritis: A Randomized Trial

Ann Intern Med. 2015 Jan 6;162(1):18-26. doi: 10.7326/M14-1030.

Abstract

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biopsy
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / adverse effects
  • Glucocorticoids / therapeutic use*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kidney / pathology
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / pathology
  • Male
  • Methylprednisolone / adverse effects
  • Methylprednisolone / therapeutic use
  • Middle Aged
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Pilot Projects
  • Prednisone / adverse effects
  • Prednisone / therapeutic use
  • Prospective Studies
  • Remission Induction
  • Tacrolimus / adverse effects
  • Tacrolimus / therapeutic use*
  • Young Adult

Substances

  • Glucocorticoids
  • Immunosuppressive Agents
  • Cyclophosphamide
  • Mycophenolic Acid
  • Prednisone
  • Tacrolimus
  • Methylprednisolone

Associated data

  • ClinicalTrials.gov/NCT00876616