title: Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide.
abstract: OBJECTIVE
  Glomerulonephritis is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low-dose IV CYC prescribed as a remission-inducing treatment, followed by azathioprine (AZA) as a remission-maintaining treatment.
  
  
  METHODS
  In this multicenter, prospective clinical trial (the Euro-Lupus Nephritis Trial [ELNT]), we randomly assigned 90 SLE patients with proliferative glomerulonephritis to a high-dose IV CYC regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by AZA. Intent-to-treat analyses were performed.
  
  
  RESULTS
  Followup continued for a median of 41.3 months in the low-dose group and 41 months in the high-dose group. Sixteen percent of those in the low-dose group and 20% of those in the high-dose group experienced treatment failure (not statistically significant by Kaplan-Meier analysis). Levels of serum creatinine, albumin, C3, 24-hour urinary protein, and the disease activity scores significantly improved in both groups during the first year of followup. Renal remission was achieved in 71% of the low-dose group and 54% of the high-dose group (not statistically significant). Renal flares were noted in 27% of the low-dose group and 29% of the high-dose group. Although episodes of severe infection were more than twice as frequent in the high-dose group, the difference was not statistically significant.
  
  
  CONCLUSIONS
  The data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis, a remission-inducing regimen of low-dose IV CYC (cumulative dose 3 gm) followed by AZA achieves clinical results comparable to those obtained with a high-dose regimen.
authors.affiliation: Cliniques Universitaires St. Luc, Université Catholique de Louvain, Brussels, Belgium. houssiau@ruma.ucl.ac.be
authors.forename: Frédéric A
authors.initials: FA
authors.lastname: Houssiau
authors.forename: Carlos
authors.initials: C
authors.lastname: Vasconcelos
authors.forename: David
authors.initials: D
authors.lastname: D'Cruz
authors.forename: Gian Domenico
authors.initials: GD
authors.lastname: Sebastiani
authors.forename: Enrique de Ramon
authors.initials: Ede R
authors.lastname: Garrido Ed
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Danieli
authors.forename: Daniel
authors.initials: D
authors.lastname: Abramovicz
authors.forename: Daniel
authors.initials: D
authors.lastname: Blockmans
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mathieu
authors.forename: Haner
authors.initials: H
authors.lastname: Direskeneli
authors.forename: Mauro
authors.initials: M
authors.lastname: Galeazzi
authors.forename: Ahmet
authors.initials: A
authors.lastname: Gül
authors.forename: Yair
authors.initials: Y
authors.lastname: Levy
authors.forename: Peter
authors.initials: P
authors.lastname: Petera
authors.forename: Rajko
authors.initials: R
authors.lastname: Popovic
authors.forename: Radmila
authors.initials: R
authors.lastname: Petrovic
authors.forename: Renato Alberto
authors.initials: RA
authors.lastname: Sinico
authors.forename: Roberto
authors.initials: R
authors.lastname: Cattaneo
authors.forename: Josep
authors.initials: J
authors.lastname: Font
authors.forename: Geneviève
authors.initials: G
authors.lastname: Depresseux
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cosyns
authors.forename: Ricard
authors.initials: R
authors.lastname: Cervera
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007677:Kidney Function Tests; D008181:Lupus Nephritis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D016037:Single-Blind Method; D017211:Treatment Failure
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D001379:Azathioprine