Immunosuppressive therapy in lupus nephritis: The Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide
Article first published online: 9 AUG 2002
Copyright © 2002 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 46, Issue 8, pages 2121–2131, August 2002
How to Cite
Houssiau, F. A., Vasconcelos, C., D'Cruz, D., Sebastiani, G. D., Garrido, E. d. R., Danieli, M. G., Abramovicz, D., Blockmans, D., Mathieu, A., Direskeneli, H., Galeazzi, M., Gül, A., Levy, Y., Petera, P., Popovic, R., Petrovic, R., Sinico, R. A., Cattaneo, R., Font, J., Depresseux, G., Cosyns, J.-P. and Cervera, R. (2002), Immunosuppressive therapy in lupus nephritis: The Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis & Rheumatism, 46: 2121–2131. doi: 10.1002/art.10461
- Issue published online: 9 AUG 2002
- Article first published online: 9 AUG 2002
- Manuscript Accepted: 30 APR 2002
- Manuscript Received: 26 OCT 2001
- European League Against Rheumatism
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.
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.
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.
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.