Tacrolimus versus mycophenolate mofetil for induction therapy of lupus nephritis: a randomised controlled trial and long-term follow-up

Ann Rheum Dis. 2016 Jan;75(1):30-6. doi: 10.1136/annrheumdis-2014-206456. Epub 2014 Dec 30.


Objective: To compare the efficacy of tacrolimus (TAC) and mycophenolate mofetil (MMF) for the initial therapy of lupus nephritis (LN).

Study design: This is an open randomised controlled parallel group study.

Methods: Adult patients with biopsy-confirmed active LN (class III/IV/V) were randomised to receive prednisolone (0.6 mg/kg/day for 6 weeks and tapered) in combination with either TAC (0.06-0.1 mg/kg/day) or MMF (2-3 g/day) for 6 months. Good responders were shifted to azathioprine for maintenance. The primary outcome was the rate of complete renal response (CR) at 6 months and the secondary outcomes included partial renal response, renal flares and decline of renal function over time.

Results: 150 patients (92% women; aged 35.5±12.8 years; 81% class III/IV) were randomised (76 MMF, 74 TAC). At month 6, the rate of CR was 59% in the MMF and 62% in the TAC group (treatment difference: 3.0% (-12%, 18%); p=0.71). Major infective episodes occurred in 9.2% patients treated with MMF and in 5.4% patients treated with TAC (p=0.53). Maintenance therapy with azathioprine was given to 79% patients. After 60.8±26 months, proteinuric and nephritic renal flares developed in 24% and 18% of patients in the MMF group and 35% (p=0.12) and 27% (p=0.21) in the TAC group, respectively. The cumulative incidence of a composite outcome of decline of creatinine clearance by ≥30%, development of chronic kidney disease stage 4/5 or death was 21% in the MMF and 22% in the TAC group of patients (p=0.35).

Conclusions: TAC is non-inferior to MMF, when combined with prednisolone, for induction therapy of active LN. With azathioprine maintenance for 5 years, a non-significant trend of higher incidence of renal flares and renal function decline is observed with the TAC regimen.

Trial registration number: Hospital Authority Research Ethics Committee Clinical Trial Registry (HARECCTR0500018; Hong Kong) and US ClinicalTrials.gov (NCT00371319).

Keywords: Lupus Nephritis; Systemic Lupus Erythematosus; Treatment.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / therapeutic use
  • Azathioprine / therapeutic use
  • Creatinine / blood
  • Creatinine / urine
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Induction Chemotherapy / methods*
  • Kidney Failure, Chronic / etiology
  • Lupus Nephritis / complications
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / physiopathology
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Prednisolone / therapeutic use
  • Proteinuria / etiology
  • Recurrence
  • Tacrolimus / adverse effects
  • Tacrolimus / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Anti-Inflammatory Agents
  • Immunosuppressive Agents
  • Prednisolone
  • Creatinine
  • Mycophenolic Acid
  • Azathioprine
  • Tacrolimus

Associated data

  • ClinicalTrials.gov/NCT00371319