Lessons From Long-Term Followup of Patients in the Euro-Lupus Nephritis Trial
Frédéric A. Houssiau, Carlos Vasconcelos, David D’Cruz, Gian Domenico Sebastiani, Enrique de Ramon Garrido, Maria Giovanna Danieli, Daniel Abramovicz, Daniel Blockmans, Alessandro Mathieu, Haner Direskeneli, Mauro Galeazzi, Ahmet Gül, Yair Levy, Peter Petera, Rajko Popovic, Radmila Petrovic, Renato Alberto Sinico, Roberto Cattaneo, Josep Font, Geneviéve Depresseux, Jean-Pierre Cosyns, and Ricard Cervera
Objective. In the Euro-Lupus Nephritis Trial (ELNT), 90 patients with lupus nephritis were randomly assigned to a high-dose intravenous cyclophosphamide (IV CYC) regimen (6 monthly pulses and 2 quarterly pulses with escalating doses) or a low-dose IV CYC regimen (6 pulses of 500 mg given at intervals of 2 weeks), each of which was followed by azathioprine (AZA). After a median followup of 41 months, a difference in efficacy between the 2 regimens was not observed. The present analysis was undertaken to extend the followup and to identify prognostic factors.
Methods. Renal function was prospectively assessed quarterly in all 90 patients except 5 who were lost to followup. Survival curves were derived using the Kaplan-Meier method.
Results. After a median followup of 73 months, there was no significant difference in the cumulative probability of end-stage renal disease or doubling of the serum creatinine level in patients who received the low-dose IV CYC regimen versus those who received the high-dose regimen. At long-term followup, 18 patients (8 receiving low-dose and 10 receiving high-dose treatment) had developed permanent renal impairment and were classified as having poor long-term renal outcome. We demonstrated by multivariate analysis that early response to therapy at 6 months (defined as a decrease in serum creatinine level and proteinuria <1 gm/24 hours) was the best predictor of good long-term renal outcome.
Conclusion. Long-term followup of patients from the ELNT confirms that, in lupus nephritis, a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen. Early response to therapy is predictive of good long-term renal outcome.