title: Tacrolimus versus mycophenolate mofetil for induction therapy of lupus nephritis: a randomised controlled trial and long-term follow-up.
abstract: OBJECTIVE
  To compare the efficacy of tacrolimus (TAC) and mycophenolate mofetil (MMF) for the initial therapy of lupus nephritis (LN).
  
  
  METHODS
  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.
  
  
  BACKGROUND
  Hospital Authority Research Ethics Committee Clinical Trial Registry (HARECCTR0500018; Hong Kong) and US ClinicalTrials.gov (NCT00371319).
authors.affiliation: Department of Medicine, Tuen Mun Hospital, Hong Kong.
authors.forename: Chi Chiu
authors.initials: CC
authors.lastname: Mok
authors.affiliation: Department of Medicine, Princess Margaret Hospital, Hong Kong.
authors.forename: King Yee
authors.initials: KY
authors.lastname: Ying
authors.affiliation: Department of Medicine, United Christian Hospital, Hong Kong.
authors.forename: Cheuk Wan
authors.initials: CW
authors.lastname: Yim
authors.affiliation: Department of Medicine, Tuen Mun Hospital, Hong Kong.
authors.forename: Yui Pong
authors.initials: YP
authors.lastname: Siu
authors.affiliation: Department of Medicine, Tuen Mun Hospital, Hong Kong.
authors.forename: Ka Hang
authors.initials: KH
authors.lastname: Tong
authors.affiliation: Department of Medicine, Tuen Mun Hospital, Hong Kong.
authors.forename: Chi Hung
authors.initials: CH
authors.lastname: To
authors.affiliation: Department of Medicine, United Christian Hospital, Hong Kong.
authors.forename: Woon Leung
authors.initials: WL
authors.lastname: Ng
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood / Q000652:urine; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D060828:Induction Chemotherapy / Q000379:methods*; D007676:Kidney Failure, Chronic / Q000209:etiology; D008181:Lupus Nephritis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011239:Prednisolone / Q000627:therapeutic use; D011507:Proteinuria / Q000209:etiology; D012008:Recurrence; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D011239:Prednisolone; D003404:Creatinine; D009173:Mycophenolic Acid; D001379:Azathioprine; D016559:Tacrolimus
keywords: Lupus Nephritis; Systemic Lupus Erythematosus; Treatment