title: Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis.
abstract: BACKGROUND
  Maintenance therapy, often with azathioprine or mycophenolate mofetil, is required to consolidate remission and prevent relapse after the initial control of lupus nephritis.
  
  
  METHODS
  We carried out a 36-month, randomized, double-blind, double-dummy, phase 3 study comparing oral mycophenolate mofetil (2 g per day) and oral azathioprine (2 mg per kilogram of body weight per day), plus placebo in each group, in patients who met response criteria during a 6-month induction trial. The study group underwent repeat randomization in a 1:1 ratio. Up to 10 mg of prednisone per day or its equivalent was permitted. The primary efficacy end point was the time to treatment failure, which was defined as death, end-stage renal disease, doubling of the serum creatinine level, renal flare, or rescue therapy for lupus nephritis. Secondary assessments included the time to the individual components of treatment failure and adverse events.
  
  
  RESULTS
  A total of 227 patients were randomly assigned to maintenance treatment (116 to mycophenolate mofetil and 111 to azathioprine). Mycophenolate mofetil was superior to azathioprine with respect to the primary end point, time to treatment failure (hazard ratio, 0.44; 95% confidence interval, 0.25 to 0.77; P = 0.003), and with respect to time to renal flare and time to rescue therapy (hazard ratio, <1.00; P < 0.05). Observed rates of treatment failure were 16.4% (19 of 116 patients) in the mycophenolate mofetil group and 32.4% (36 of 111) in the azathioprine group. Adverse events, most commonly minor infections and gastrointestinal disorders, occurred in more than 95% of the patients in both groups (P = 0.68). Serious adverse events occurred in 33.3% of patients in the azathioprine group and in 23.5% of those in the mycophenolate mofetil group (P = 0.11), and the rate of withdrawal due to adverse events was higher with azathioprine than with mycophenolate mofetil (39.6% vs. 25.2%, P = 0.02).
  
  
  CONCLUSIONS
  Mycophenolate mofetil was superior to azathioprine in maintaining a renal response to treatment and in preventing relapse in patients with lupus nephritis who had a response to induction therapy. (Funded by Vifor Pharma [formerly Aspreva]; ALMS ClinicalTrials.gov number, NCT00377637.).
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill, USA. neil.solomons@viforpharma.com
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Dooley
authors.forename: David
authors.initials: D
authors.lastname: Jayne
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Ginzler
authors.forename: David
authors.initials: D
authors.lastname: Isenberg
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Olsen
authors.forename: David
authors.initials: D
authors.lastname: Wofsy
authors.forename: Frank
authors.initials: F
authors.lastname: Eitner
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Appel
authors.forename: Gabriel
authors.initials: G
authors.lastname: Contreras
authors.forename: Laura
authors.initials: L
authors.lastname: Lisk
authors.forename: Neil
authors.initials: N
authors.lastname: Solomons
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007239:Infections / Q000209:etiology; D053208:Kaplan-Meier Estimate; D008181:Lupus Nephritis / Q000188:drug therapy*; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010352:Patient Dropouts; D055502:Secondary Prevention; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D001379:Azathioprine