title: Induction therapy with short-term high-dose intravenous cyclophosphamide followed by mycophenolate mofetil in proliferative lupus nephritis.
abstract: BACKGROUND
  For decades, high-dose intravenous cyclophosphamide (ivCY) given for 24-30 months was regarded as the standard therapy for proliferative lupus nephritis, despite serious side effects. Our aim was to evaluate the effect of induction therapy with short-term high-dose ivCY followed by mycophenolate mofetil (MMF) on disease parameters, mortality and health-related quality of life (HRQoL) in patients with proliferative lupus nephritis.
  
  
  METHODS
  Between January 2003 and November 2006, 71 patients with biopsy-proven proliferative lupus nephritis were included in the second Dutch Lupus Nephritis Study. All patients were treated with ivCY (750 mg÷m2, six monthly pulses) plus oral prednisone, followed by MMF (2000 mg÷day) plus oral prednisone for 18 months, and then azathioprine (2 mg÷kg÷day) plus oral prednisone. Study endpoints included the occurrence of renal relapse, end-stage renal disease (ESRD) and mortality.
  
  
  RESULTS
  After a median follow-up of 3.8 years (range 0.1-4.5), four (5.6%) of the 71 patients had a renal relapse, one (1.4%) failed treatment, one (1.4%) reached ESRD, and two (2.8%) died. Systemic lupus erythematosus (SLE) Disease Activity Index, serum creatinine, proteinuria and antibodies against anti-dsDNA decreased significantly during treatment and serum levels of complement factor 3 and 4 increased significantly. Furthermore, six of eight domains of the Short Form-36 as well as the number of symptoms and total distress level according to the SLE Symptom Checklist improved significantly over time.
  
  
  CONCLUSIONS
  This open-label study shows that induction therapy with short-term (six monthly pulses) high-dose ivCY followed by MMF is effective in preventing renal relapses, ESRD and mortality and improving HRQoL in patients with proliferative lupus nephritis.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Arends
authors.forename: J H M
authors.initials: JH
authors.lastname: Berden
authors.forename: C
authors.initials: C
authors.lastname: Grootscholten
authors.forename: R H W M
authors.initials: RH
authors.lastname: Derksen
authors.forename: S P
authors.initials: SP
authors.lastname: Berger
authors.forename: R G L
authors.initials: RG
authors.lastname: de Sévaux
authors.forename: A E
authors.initials: AE
authors.lastname: Voskuyl
authors.forename: M
authors.initials: M
authors.lastname: Bijl
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D060828:Induction Chemotherapy / Q000379:methods*; D007676:Kidney Failure, Chronic / Q000209:etiology; D008181:Lupus Nephritis / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011241:Prednisone / Q000627:therapeutic use; D011788:Quality of Life; D012008:Recurrence; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D009173:Mycophenolic Acid; D001379:Azathioprine; D011241:Prednisone