Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide.
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.
Houssiau
Frédéric A
FA
Cliniques Universitaires St. Luc, Université Catholique de Louvain, Brussels, Belgium. houssiau@ruma.ucl.ac.be
Vasconcelos
Carlos
C
D'Cruz
David
D
Sebastiani
Gian Domenico
GD
Garrido Ed
Enrique de Ramon
Ede R
Danieli
Maria Giovanna
MG
Abramovicz
Daniel
D
Blockmans
Daniel
D
Mathieu
Alessandro
A
Direskeneli
Haner
H
Galeazzi
Mauro
M
Gül
Ahmet
A
Levy
Yair
Y
Petera
Peter
P
Popovic
Rajko
R
Petrovic
Radmila
R
Sinico
Renato Alberto
RA
Cattaneo
Roberto
R
Font
Josep
J
Depresseux
Geneviève
G
Cosyns
Jean-Pierre
JP
Cervera
Ricard
R
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
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D001379:Azathioprine