Long-term outcome of a randomised controlled trial comparing tacrolimus with mycophenolate mofetil as induction therapy for active lupus nephritis

Ann Rheum Dis. 2020 Aug;79(8):1070-1076. doi: 10.1136/annrheumdis-2020-217178. Epub 2020 May 24.


Objectives: To report the 10-year outcome of lupus nephritis (LN) treated with mycophenolate mofetil (MMF) or tacrolimus (TAC) induction in a randomised controlled trial.

Methods: Patients with active LN were treated with MMF or TAC combined with high-dose prednisolone. Responders were switched to azathioprine (AZA) at month 6. Clinical outcomes at 10 years (renal flares, renal function decline and mortality) were assessed. Factors affecting prognosis were studied by Cox regression. Urine protein-to-creatinine ratio (uPCr) and estimated glomerular filtration rate (eGFR) at different time points were evaluated for their prediction of a poor prognosis by receiver operating characteristic (ROC) analysis.

Results: 150 patients were studied (age 35.5±12.8 years). Complete renal response rate was similar between MMF (59%) and TAC-treated patients (62%; p=0.71). AZA maintenance was given to 79% patients. After 118.2±42 months, proteinuric and nephritic renal flares occurred in 34% and 37% of the MMF, and 53% and 30% of the TAC groups of patients, respectively (p=0.49). The cumulative incidence of a composite outcome of ↓eGFR ≥30%, chronic kidney disease stage 4/5 or death at 10 years was 33% in both groups (p=0.90). Factors independently associated with a poor renal prognosis were first-time LN (HR 0.12 (0.031 to 0.39); p=0.01), eGFR (HR 0.98 (0.96 to 0.99); p=0.008) and no response at month 6 (HR 5.18 (1.40 to 19.1); p=0.01). ROC analysis revealed an uPCr >0.75 and eGFR of <80 mL/min at month 18 best predicted a poor renal prognosis.

Conclusions: Long-term data confirmed non-inferiority of TAC to MMF as induction therapy of LN. An uPCr≤0.75 and eGFR of ≥80 mL/min at month 18 best predicted a favourable 10-year outcome and may be suitable targets for induction/consolidation therapy.

Trial registration number: NCT00371319.

Keywords: lupus nephritis; outcomes research; systemic lupus erythematosus; treatment.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Azathioprine / therapeutic use
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Induction Chemotherapy / methods*
  • Lupus Nephritis / drug therapy*
  • Maintenance Chemotherapy / methods
  • Male
  • Middle Aged
  • Mycophenolic Acid / therapeutic use*
  • Prednisolone / therapeutic use
  • Symptom Flare Up
  • Tacrolimus / therapeutic use*
  • Time
  • Treatment Outcome


  • Enzyme Inhibitors
  • Immunosuppressive Agents
  • Prednisolone
  • Mycophenolic Acid
  • Azathioprine
  • Tacrolimus

Associated data

  • ClinicalTrials.gov/NCT00371319